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Hager, Michele LynnManecaA Study of Contact Lens Comfort in Patients Wearing Comfilcon A Soft Contact Lenses Compared to Their Habitual Soft Contact Lenses
Master of Science, The Ohio State University, 2009, Vision Science
Contact lens discomfort, especially contact lens-related ocular dryness, is a major cause of contact lens wear discontinuation. Many studies have evaluated different contact lens materials for their comfort in both normal patients and sufferers of contact lens-related dry eye. This study seeks to evaluate a new silicone hydrogel soft contact lens material (comfilcon A) in terms of comfort, measurable tear film parameters, and total contact lens-extracted lipid in normal and contact lens-related dry eye contact lens wearers as compared to their habitual contact lenses. Thirty four participants completed this study consisting of two visits—the first with participant wearing their habitual soft contact lenses and the second with the study contact lenses. Interferometric measurements of the pre-lens tear film thinning rate (PLTF thinning rate), the lipid layer thickness (LLT), and the initial pre-lens tear film thickness (PLTF) were recorded, the Contact Lens Dry Eye Questionnaire (CLDEQ) was peformed, and the participants’ lenses were collected for lipid analysis at each visit. The CLDEQ scores at the first study visit of the non-dry eye and dry eye group were shown to be significantly different from one another (p <0.0001). Total extracted lipid amounts showed a significant difference for the non-dry eye group between the first and second study visits (p = 0.01) but not for the dry eye group (p = 0.10). A significant correlation was found between LLT and PLTF thinning rate for the first visit (r = 0.39, p = 0.03), but not for the second visit (r = 0.14, p = 0.43). A significant correlation was found between CLDEQ score and PLTF thinning rate for the dry eye group (rs = -0.55, p = 0.03) but not for the non-dry eye group (rs = 0.11, p = 0.71) at the first visit. A significant correlation was found between CLDEQ score and LLT for the non-dry eye group (rs = -0.53, p = 0.04) but not for the dry eye group (rs = -0.18, p = 0.53) at the first visit. A significant correlation was found between contact lens-extracted lipid quantity and number of days for which the habitual contact lenses were worn (r = 0.37, p = 0.03). One month of wear of comfilcon A silicone hydrogel contact lenses did not significantly improve subjective dryness symptom severity in either normals or contact lens-related dry eye sufferers as compared to their habitual lens materials. Further research is needed to determine a quantifiable tear film parameter or other marker by which to diagnose or grade contact lens-related dry eye and is also needed to find or develop a soft contact lens material that can be comfortably worn by contact lens-related dry eye sufferers.

Committee:

Jason Nichols, OD, PhD, MPH (Advisor); Kelly Nichols, OD, PhD, MPH (Committee Member); P. Ewen King-Smith, PhD (Other)

Subjects:

Ophthalmology

Keywords:

dry eye; comfilcon A; interferometry; lipid layer thickness; pre-lens tear film thinning rate; pre-lens tear film thickness; contact lens dry eye questionnaire

Zhao, HaotianExploring the role of fibroblast growth factor (FGF) signaling in mouse lens fiber differentiation through tissue-specific disruption of FGF receptor gene family
Doctor of Philosophy, The Ohio State University, 2004, Molecular, Cellular, and Developmental Biology
The vertebrate lens provides an excellent model to study mechanisms of cell cycle regulation and differentiation. Lens is composed of proliferative epithelium covering the anterior hemisphere and a core of postmitotic fiber cells that are differentiated from the epithelial cells at the lens equator. However, relatively little is known about the identity of molecules in the ocular environment that promote fiber differentiation in vivo. Despite circumstantial evidence suggesting the importance of Fibroblast Growth Factor (FGF) signaling in lens development, its role during lens development in vivo is still unclear and controversial. FGFs act through binding and activation of FGF receptors (FGFRs). The mouse lens expresses at least 3 different FGFR genes (Fgfr1-3) in a dynamic spatio-temporal fashion. In this study, we examined the role of FGF receptor signaling in lens fiber differentiation by targeting Fgfrs individually or in different combinations. To address the role of Fgfr1 and Fgfr2, null mutations of which cause early embryonic lethality prior to ocular induction, in lens development, we performed chimeric analysis and tissue-specific gene inactivation. To achieve lens-specific gene ablation, a transgenic mouse line, MLR10, was generated using this modified alphaA-crystallin promoter that drives Cre recombinase expression in a lens-specific manner from embryonic days 10.5 (E10.5). Our analyses showed that lens fiber differentiation was not prevented in the absence of any single Fgfr. Given the possibility of redundancy among different Fgfrs during lens fiber differentiation, we proceeded to inactivate Fgfrs in different combinations. Histological and gene expression analyses indicated that lens fiber differentiation was intact in all double Fgfr mutants. However, profound lens defects were observed in mice lacking all three Fgfrs. Lens-specific inactivation of Fgfrs causes abnormal proliferation, reduced expression of cell cycle inhibitors p27kip1 and p57kip2 and transcription factor Prox1, misexpression of E-cadherin and increased apoptosis. Moreover, deficiency in FGF signaling suppressed alpha-, beta- and gamma-crystallin expression through downregulation of transcription factor c-Maf and misexpression of Pax6. Consequently, mutant lens cells failed to polarize and elongate properly, forming a hollow lens. Our study demonstrated that FGF signaling integrates cell cycle regulation with differentiation pathways to establish polarized lens structure in vivo.

Committee:

Michael Rbinson (Advisor)

Subjects:

Biology, Genetics

Keywords:

lens development; lens epithelium; lens fiber; differentiation; cell cycle; proliferation; Pax6; c-Maf; FGF; receptor tyrosine kinase; transgenic; conditional knockout

He, PengDesign and Fabrication of Nonconventional Optical Components by Precision Glass Molding
Doctor of Philosophy, The Ohio State University, 2014, Industrial and Systems Engineering
Precision glass molding is a net-shaping process to fabricate glass optics by replicating optical features from precision molds to glass at elevated temperature. The advantages of precision glass molding over traditional glass lens fabrication methods make it especially suitable for the production of optical components with complicated geometries, such as aspherical lenses, diffractive hybrid lenses, microlens arrays, etc. Despite of these advantages, a number of problems must be solved before this process can be used in industrial applications. The primary goal of this research is to determine the feasibility and performance of nonconventional optical components formed by precision glass molding. This research aimed to investigate glass molding by combing experiments and finite element method (FEM) based numerical simulations. The first step was to develop an integrated compensation solution for both surface deviation and refractive index drop of glass optics. An FEM simulation based on Tool-Narayanaswamy-Moynihan (TNM) model was applied to predict index drop of the molded optical glass. The predicted index value was then used to compensate for the optical design of the lens. Using commercially available general purpose software, ABAQUS, the entire process of glass molding was simulated to calculate the surface deviation from the adjusted lens geometry, which was applied to final mold shape modification. A case study on molding of an aspherical lens was conducted, demonstrating reductions in both geometry and wavefront error by more than 60%. In addition, mold materials and mold fabrications were explored as molds are crucial for fabrication of different freeform optics. The research for the first time demonstrated the use of graphene-coated silicon as an effective and high-performance mold material for precision glass molding. It was shown experimentally that Si-glass adhesion could be completely avoided by using the carbide-bonded graphene coating on Si molds. A glass Fresnel lens and a micro lens arrays using graphene-coated Si molds were molded and tested. Two other novel mold materials, i.e., bulk material glass and copper nickel alloy, were also investigated. Prototypes of optical components were molded using these two materials. The molded lens glass samples were measured by 3D profiler, and the optical performance of the molded lens was also evaluated by lab optical setup. The applications of both of the mold materials were also discussed. Finally, precision glass molding techniques are discussed for two different applications, a diffractive hybrid lens molded by a visible optical glass and a micro lens array molded by infrared (IR) glass. The diffractive hybrid lens was designed to compensate for chromatic aberration. The diffractive efficiency and achromatic focal shift of the molded lens were measured using lab setup, demonstrating a match between the molded lens and optical design. On the other hand, an infrared glass micro lens array and optical gratings were also molded and evaluated using similar approach. The geometry and optical evaluation of these molded glass applications showed that precision glass molding are capable of fabricate non-convectional optical components with designed functionality.

Committee:

Allen Yi (Advisor); Jose Castro (Committee Member); James Lee (Committee Member)

Subjects:

Engineering; Experiments; Industrial Engineering; Materials Science; Mechanical Engineering

Keywords:

Precision glass molding; Optical fabrication; Mold material; Optical design; Infrared glass molding; Graphene ; Coating; Lens fabrication; Micro lens array ; Diffractive lens

Szczotka-Flynn, Loretta B.The Longitudinal Analysis of Silicone Hydrogel Contact Lens Study
Doctor of Philosophy, Case Western Reserve University, 2010, Epidemiology and Biostatistics
The Longitudinal Analysis of Silicone Hydrogel Contact Lens Study (LASH Study) was a prospective cohort study of silicone hydrogel contact lens wearers who slept in their lenses for up to 29 consecutive nights (30 days) of continuous wear, with monthly disposal. Two hundred five healthy myopic or hyperopic patients with minimal or no astigmatism and no contraindications to continuous wear lens use were followed for 1 year. The primary outcome measure was the time to development of a corneal infiltrative event as defined by slit lamp findings and patient symptoms. Survival analysis techniques were used to assess key predictor variables as potential risk factors. The main exposure of interest was corneal staining followed by bacterial contamination of study lenses. Bacterial contamination was found to be common with continuous wear use of silicone hydrogel lenses and the primary risk factor for development of a corneal infiltrative event. Corneal staining was not associated with the development of a corneal infiltrative event. Alteration of the protective mucus layer of the tear film as evidenced by mucin balls trapped behind the lens was found to play a protective role. This information will be helpful for practitioners as they select and monitor patients for this mode of lens wear, and for manufacturers as they design future generations of contact lenses.

Committee:

Alfred Rimm, PhD (Committee Chair); Sara Debanne, PhD (Committee Member); Ajay Sethi, PhD (Committee Member); Jonathan Lass, MD (Committee Member); Desmond Fonn, MOptom (Committee Member)

Subjects:

Epidemiology; Health Care; Microbiology; Ophthalmology

Keywords:

contact lens; corneal infiltrative events; contact lens microbial contamination

Nixon, Alex DVisual Performance of Scleral and Soft Contact Lenses in Normal Eyes
Master of Science, The Ohio State University, 2014, Vision Science
The purpose of this study is to investigate whether scleral lenses have vision performance advantages compared to soft contact lenses in normal eyes. Previous studies reported that rigid contact lenses can increase or decrease optical aberrations of the eye depending on the quantity of aberrations at baseline.1 Soft contact lenses have generally increased optical aberrations compared to baseline. 2 3 Conclusions regarding optical quality with contact lenses have been inconsistent due to variability in study design, variability in contact lens parameters, differing lens fitting protocols, the specific measurements taken and the instruments used to take those measurements. This study will minimize variability due to rigid lens decentration and movement on eye by using a larger, more stable scleral design. The study will also include clinically relevant vision performance testing such as high contrast visual acuity, low contrast visual acuity, and contrast sensitivity. The hypothesis is that scleral lenses improve vision performance compared to soft contact lenses due to a reduction in optical aberrations of the eye. 14 subjects were fit with the Onefit P&A (Blanchard Lab, Manchester, NH) and Air Optix Aqua or Air Optix for Astigmatism (Alcon, Ft. Worth, TX) contact lenses. Measurements were taken at baseline and separate lens evaluation visits scheduled after completion of the contact lens fits. The order the contact lenses were worn was randomized and the lenses were worn for six hours prior to each lens evaluation visit. The primary outcomes were Bailey-Lovie high and low contrast visual acuity (10% Michelson), MARS contrast sensitivity, and higher-order aberrations, measured with the Complete Ophthalmic Analysis System (COAS). Secondary outcomes were scleral lens clearance and sodium fluorescein corneal epithelial staining. The corneal clearance was estimated using images from the Heidelberg Spectralis optical coherence tomographer. There was no difference between the contact lenses in measurements of high contrast visual acuity (p=0.61), low contrast visual acuity (p=0.96), and contrast sensitivity (p=0.30). The Air Optix lenses had significantly reduced coma Z(3,1). The Onefit P&A lenses had significantly reduced trefoil Z(3,3) (p=0.01) and spherical aberration Z(4,0) (p<0.01). The Onefit P&A lens tended to have lower root-mean-square (RMS), but the trend was not statistically significant (p=0.51). The average Onefit P&A clearance after six hours of wear was 159 ± 64 microns. The average Onefit P&A settling after six hours of wear was 91.71 microns. Corneal epithelial staining was present following six hours of wear in 4/14 (29%) eyes wearing Air Optix lenses and 13/14 (93%) of eyes wearing Onefit P&A lenses. The Onefit P&A rigid lenses do not appear to reduce aberrations in a population of normal eyes, consistent with previous studies.1,3 In addition, there was no detectable difference between the Onefit P&A and Air Optix lenses in tests of visual performance including high contrast visual acuity, low contrast visual acuity, and contrast sensitivity. While rigid lenses may anecdotally offer improved optical quality, this population of normal eyes with relatively low astigmatism did not demonstrate a clinically significant difference. While Onefit P&A lenses offer promising improvements in comfort and stability compared to traditional rigid lenses, the lens designs require further evaluation to ensure safety and to streamline the fitting process.

Committee:

Dean VanNasdale (Advisor); Aaron Zimmerman (Committee Member); G. Lynn Mitchell (Committee Member)

Subjects:

Biomedical Research; Medicine; Ophthalmology; Optics

Keywords:

Scleral contact lens; higher-order aberrations; contact lens; wavefront aberrations; settling; epithelial staining; epithelial bullae; vision performance; optical coherence tomography; OCT

Nichols, Jason JayEvaporative tear film and contact lens factors associated with dry eye symptoms in contact lens wearers
Doctor of Philosophy, The Ohio State University, 2004, Physiological Optics

The Contact Lens and Dry Eye Study (CLADES) is a cross-sectional/nested case-control study designed to study tear film, contact lens, ocular surface, and patient-related factors associated with self-reported dry eye disease in contact lens wearers. Data from 325 patients in the CLADES database were used for these analyses. Two datasets were assembled in order to determine tear film, contact lens, and patient-related factors associated with self-reported dry eye. The full dataset (n = 325) includes all patients in the original dataset and the clean dataset (n = 216) includes only patients who completed the CLDEQ on two occasions and who did not misclassify their disease status upon re-administration of the survey.

Factors that contributed significantly to the prediction of disease status across both the full and clean datasets included gender (p < 0.0001 and 0.006, respectively) and meibomian gland count (p = 0.02 and 0.03, respectively). However, the result for meibomian gland count was opposite of what was expected (e.g., more whole glands counted was associated with dry eye disease). Other factors that showed significance in the analysis of the clean dataset included osmolarity (p = 0.02), nominal water content (p = 0.03), and pre-lens tear film noninvasive breakup time (p = 0.03). No analyses showed a relation between measured dehydration and dry eye status, either when grouped together, or for specific contact lens types.

In summary, classification issues relating to contact lens-related dry eye studies significantly impact the internal validity of the sample, and these data provide some initial insight into these issues. Several factors were found to be associated with contact lens-related dry eye including gender (females), increased osmolarity, and decreased pre-lens non-invasive breakup time. The data are not consistent with the hypothesis that contact lens wear leads to alterations of meibomian gland structure. Yet, contact lens wear seems to alter the pre-lens lipid layer in a way that was not measured by the outcomes of this study. Future studies will need to address alternative hypotheses as they relate to the pre-lens tear film and dry eye during contact lens wear.

Committee:

Karla Zadnik (Advisor)

Keywords:

contact lens; dry eye; hydrogel; wettability; lipid layer; pre-lens tear film

Hoang, Thanh VTRANSCRIPTIOME ANALYSIS AND EPIGENETIC REGULATION OF OCULAR LENS DEVELOPMENT
Doctor of Philosophy, Miami University, 2016, Biology
The ocular lens is an excellent model to study cell signaling, cell survival and cell differentiation. The lens is comprised of only two cell types: proliferative lens epithelial cells and terminally differentiated lens fiber cells. The lens fiber differentiation process involves specific changes in gene expression between the two cell types. However, a comprehensive understanding of gene expression changes during lens fiber differentiation remains incomplete. Furthermore, despite the wealth of knowledge of transcription factors involved in lens cell proliferation, survival and lens fiber differentiation, little information exists about the role of DNA methylation and miRNAs in these processes. This study presents the first application of RNA-seq to provide a comprehensive view of both the relative abundance and differential expression of mRNAs and long intergenic non-coding RNAs from lens epithelial cells and lens fiber cells. We also investigated the role of DNA methylation in lens development. We found that while Dnmt1 inactivation at the lens placode stage led to lens DNA hypomethylation and severe lens epithelial apoptosis, lens fiber cell differentiation remained largely unaffected. The simultaneous deletion of phosphatase and tensin homolog (Pten) elevated the level of phosphorylated AKT and rescued many of the morphological defects and cell death in DNMT1- deficient lenses. With a different Cre driver (MLR10) we demonstrated that a small number of lens epithelial cells escaped Dnmt1-deletion and over-proliferated to compensate for the loss of Dnmt1-deleted cells, suggesting that lens epithelium possess a substantial capacity for self- renewal. Inactivation of both Dnmt3a and Dnmt3b by either the Le-Cre or MLR10-Cre transgene did not result in any obvious lens phenotype prior to 10 months of age, indicating that de novo DNA methylation, at least as mediated by both DNMT3A and DNMT3B, is dispensable for normal lens development. Our comparative miRNA-Seq data analysis showed that the mouse lens expresses over 350 known miRNAs. Despite of high expression of miR-1-3p in the lens fiber, we did not find any obvious morphological defects in single and double miR-1-1 and miR- 1-2 knockout lenses. Likewise, mice deficient in miR-184 also appear to be normal. Deleting one or two out of three miR-26 family members (miR-26a1, miR-26a2 and miR26b) also did not result in any obvious defect. However, loss of all three miR-26 family members caused severe nuclear cataract in adult mice. Together, our results support the view that deletion of many miRNAs is tolerated in mice due to redundancies between miRNAs and between different pathways.

Committee:

Michael Robinson (Advisor)

Subjects:

Biology; Biomedical Research; Genetics; Zoology

Keywords:

Lens; epithelial cells; fiber cells; RNA sequencing; small RNA sequencing; differential expression; DNMT1; DNMT3A; DNMT3B; miRNA; Crispr, Cas9; miR-1; miR-184; miR-26a; miR-26b; knockout; lens development; fiber cell differentiation; cataract

Long, Amy CariseInfluence of environmental and chemical factors on cellular signaling in lens epithelial cells
Doctor of Philosophy, The Ohio State University, 2007, Human Nutrition and Food Management
Cataract is the leading cause of vision loss worldwide and is treated only by surgical intervention. Oxidative stress-induced damage to the lens can accumulate with aging or exposure to environmental and/or chemical stressors. Lens epithelial cells (LEC) comprise the first cell layer exposed to stress, and LEC death is considered an initiating event in cataract development. Activation of stress-induced cell signaling pathways coordinates the LEC response to injury. The first objective of this research was to determine the mechanism(s) of cell death in human lens epithelial cells (HLE) exposed to environmental (ultraviolet B (UVB) radiation) and chemical stressors (hydrogen peroxide, (H 2O 2) and tertiary butyl hydroperoxide, (TBHP)). While all three stressors decreased HLE cell density, exposure to UVB resulted in changes in cell morphology, DNA fragmentation and annexin/propidium iodide staining consistent with apoptosis, whereas H 2O 2and TBHP treatment resulted in necrosis. Activation of signaling proteins such as JNK, c-Jun and DNA fragmentation factor 45 (DFF45) were observed only in UVB-treated cells. Gap junction intercellular communication (GJIC) facilitates nutrient transport in the lens, and is regulated by cell stress, cell signaling pathways and dietary compounds. The mechanism of this regulation is not clearly established, although changes in connexins, structural proteins of gap junction channels, is involved. Connexin 43 (Cx43) is the major connexin present in LEC. The second objective of this research was to examine the role of cell signaling pathways and the dietary compounds, retinoids and carotenoids, in modulating GJIC in canine LEC. Treatment with the protein kinase C (PKC) activator, TPA, significantly decreased GJIC in canine LEC and increased Cx43 phosphorylation. Inhibition of PKC partially restored TPA-inhibited GJIC and reduced Cx43 phosphorylation. Retinoic acid increased expression of Cx43 and enhanced GJIC in canine LEC. LEC utilize stress-induced signaling pathways to respond to environmental and chemical stressors. GJIC can be regulated by cell signaling pathways and dietary compounds in primary canine LEC. The long term application of this project includes a better understanding of the molecular mechanisms by which various stressors and dietary compounds modulate lens physiology and cataractogeneis in humans and animals.

Committee:

Joshua Bomser (Advisor)

Subjects:

Health Sciences, Nutrition

Keywords:

lens epithelial cell; cell signaling; environmental stress; chemical stress; primary canine lens; apoptosis; gap junction communication; connexin; retinoids; carotenoids; antioxidant; cataract

Baddour, JoelleAn Approach to Lens Regeneration in Mice Following Lentectomy and the Implantation of a Biodegradable Hydrogel Encapsulating Iris Pigmented Tissue in Combination with Basic Fibroblast Growth Factor
Master of Science (M.S.), University of Dayton, 2012, Chemical Engineering
Organ or tissue regeneration is the process by which damaged or lost tissue parts or whole body organs are repaired or replaced. When compared to amphibians, mammals possess very limited regenerative capabilities. Mammals are capable of lens regeneration following lentectomy only if the lens capsule is left behind. Regeneration is achieved by the residual lens epithelial cells (LECs) adherent to the remaining lens capsule. Urodele amphibians, however, have been reported to regenerate their lenses, following whole organ removal, by the transdifferentiation of the pigmented epithelial cells (PECs) of the dorsal iris. These cells, namely PECs, have been shown to possess a potential for transdifferentiation in vitro as well as in vivo. In this study, the feasibility of coaxing iris PECs to regenerate a lens in vivo was tested by encapsulating an iris pigmented epithelial tissue by a hydrogel bead combined with FGF and implanting the resulting matrix in lentectomized mice. This study also investigates the ability of aligned Poly-ε-caprolactone (PCL) nanofibers in inducing the differentiation of LECs and the subsequent alignment of lens fiber cells.

Committee:

Panagiotis A Tsonis, PhD (Committee Chair); Robert J Wilkens, PhD (Committee Member); Amit Singh, PhD (Committee Member)

Subjects:

Biology; Biomedical Engineering; Biomedical Research; Chemical Engineering; Developmental Biology

Keywords:

Lens Regeneration; Iris Pigmented Epithelial Cells; Lens Epithelial Cells; Transdifferentiation; Differentiation; Fibroblast Growth Factor (FGF); Hydrogel; Poly-&949;-caprolactone (PCL); Nanofibers; Mouse

Mital, RashmiDesign and demonstration of a novel optical true time delay technique using polynomial cells based on white cells
Doctor of Philosophy, The Ohio State University, 2005, Electrical Engineering
This dissertation presents the design of an octic-style optical true-time delay cell and a proof-of-concept experimental demonstration of a subset of it. The octic cell is a “polynomial” cell, which is one of two classes of true time delay cells being designed by our group. The octic cell is designed to produce a maximum of 6399 sequential delays (or more than 12 bits of delay) in 17 bounces for a given light beam through the apparatus with a unit delay of 3ps. The largest delay in the octic cell is 19.197 ns. We use both glass blocks for small delays and lens trains for the longer delays. The octic cell is designed to use a micro-electrical mechanical systems or MEMS device, which consists of tip/tilt micromirror array to direct the light beams in various directions on each bounce. White cells of different lengths are set up in each of these different directions. By forcing the light to travel the different lengths, we are able to obtain different delays. For our proof-of-concept experiment, we set up only six of the ten arms of the octic cell (arms C, D, J and K and the null arms A and B) as a planar quartic cell. With the use of a Calient® MEMS device, we were able to demonstrate switching of light between the different arms by just tipping the right micro mirrors. The experimental results also proved that it is possible to use glass blocks as delays elements for short delays with lens trains for longer delays. We were able to measure delays with an accuracy of 0.5ps with a E8320B Network Analyzer. A detailed step-by-step description of the alignment procedure used in the setting up of the quartic cell has also been described in the dissertation. Finally, a simulation of the quartic cell in OSLO showed that the quartic cell using a single field lens tends to suffer from spherical aberrations. Further simulations showed that by using separate field lenses we are able to rid the cell of spherical aberrations.

Committee:

Betty Lise Anderson (Advisor)

Keywords:

mirrors; WHITE CELLS; beam; arms; field lens; glass blocks; lens

Tuten, William ScottAnterior Segment Optical Coherence Tomography-Based Phakometry Measurements in Children
Master of Science, The Ohio State University, 2009, Vision Science
Anterior segment optical coherence tomography (AS-OCT) is emerging as a valuable tool for in vivo ocular biometry. This study constitutes the first known attempt at in vivo assessment of crystalline lens curvature using AS-OCT technology. METHODS: An ASOCT phakometry protocol was compared to video-based phakometry data on a sample of 42 children. RESULTS: AS-OCT phakometry demonstrated poor 95% limits of agreement (LOA) and significant magnitude bias, yielding excessively flat radii when used to measure flatter surfaces (anterior: P < 0.001, LOA = -8.82 to +6.52 mm; posterior: P < 0.001, LOA = -1.13 to +1.67 mm). Orthogonal regression-derived correction neutralized the posterior surface magnitude bias only (P = 0.206, LOA = -0.78 to +0.83 mm). CONCLUSIONS: AS-OCT phakometry of the anterior lens surface compared poorly to video-based methods, likely due to errors introduced by nonrepeatable locations for the cross-sectional scans through the crystalline lens.

Committee:

Donald Mutti, PhD (Advisor); Melissa Bailey, PhD (Committee Member); Thomas Raasch, PhD (Committee Member)

Subjects:

Optics

Keywords:

phakometry; crystalline lens; Optical Coherence Tomography

Schultz, Kristin E.Accommodative microfluctuations, crystalline lens tension, ciliary body thickness, and refractive error in children
Master of Science, The Ohio State University, 2009, Vision Science

Purpose: To investigate the relationship between microfluctuations in accommodation, resting tension on the crystalline lens, ciliary body thickness, and refractive error in children.

Methods: Subjects were 49 children, ages eight to 15 years. Subjects wore habitual correction over their left eye and an infrared filter over the right eye during accommodative measurements. Monocular accommodation was measured continuously for two, 30-second periods using a PowerRef I at a sampling rate of 25 Hz while subjects viewed a high-contrast target at 0.25 m. The high (1.0-2.3 Hz) and low (0-0.6 Hz) frequency components of the power spectrum from a Fast Fourier Transform of the accommodative response were used in analysis. Resting tension on the crystalline lens was assessed by measuring the amplitude of the oscillations of the crystalline lens following a rightward 20° saccadic eye movement. Ciliary body thickness was measured two millimeters posterior to the scleral spur from images obtained with a Zeiss Visante™ OCT. Cycloplegic spherical equivalent refractive error was obtained with the Grand Seiko autorefractor.

Results: The mean ± SD spherical equivalent refractive error was -1.00 D ± 2.25 (range -6.00 D to +3.44 D). Greater power in the high-frequency component of accommodative microfluctuations was associated with thinner ciliary bodies, lower ages and more hyperopic refractive errors. No statistically significant relationship was found for the low-frequency component or root mean square of accommodative microfluctuations and refractive error.

Conclusions: High-frequency microfluctuations of accommodation appear to be suppressed with thicker ciliary bodies. These variations in accommodation need to be observed in a longitudinal study to better assess the functional significance of their relationship to ciliary body size and refractive error.

Committee:

Melissa Bailey, OD, PhD (Advisor); Don Mutti, OD, PhD (Committee Member); Marjean Taylor Kulp, OD, PhD (Committee Member)

Subjects:

Ophthalmology; Optics

Keywords:

myopia; accommodation; crystalline lens; ciliary body; children

Wenzel, Pamela L.Role of the RB-E2F pathway in embryonic development: implications for paradigms of cell cycle control
Doctor of Philosophy, The Ohio State University, 2007, Molecular Genetics
The Rb-E2F pathway has been the focus of a tremendous body of research, due in large part to its well-recognized role in tumorigenesis. We report in this study a role for Rb in limiting proliferation of trophoblast stem cells during development of the mouse placenta. These findings point to a critical role for Rb at a time when stem cells are beginning to differentiate. We also address the role of Rb binding partners, E2F1, E2F2, and E2F3, in stem and progenitor cell biology in vivo and in vitro. We find that these transcriptional activators are largely dispensable for proliferation in pluripotent stem cells and in many differentiated cell types; however, E2F1-3 do appear to be critical for cell cycle regulation and survival during and after differentiation of specific lineages. Further, we explore the implications of our findings for the current paradigm of E2F function and consider novel roles for E2F that may be largely independent of transcriptional control of cell cycle-regulated gene expression. Appreciating how these genes function in stem cells will be key to understanding how they impact the cell cycle, senescence, self-renewal, proliferation, apoptosis, and differentiation programs during normal development and tumorigenesis.

Committee:

Gustavo Leone (Advisor)

Keywords:

Rb; E2F; Transcription factors; Development; Placenta; Trophoblast; Stem cells; Lens; Apoptosis; Differentiation; Proliferation; Cell cycle

Miller, Eric J"Effects of Grape Seed Extract, Lutein, and Omega-3 Fatty Acids on Lens Epithelial Cell Behavior In Vitro and Ex Vivo"
Master of Science, The Ohio State University, 2014, Comparative and Veterinary Medicine
The purpose of this study was to determine if grape seed extract (GSE), lutein, and omega-3 fatty acids (O3FA), alter oxidative stress, migration, and proliferation in lens epithelial cells (LECs). An antioxidant reductive capacity assay determined the reducing capability of each antioxidant. Then following antioxidant treatment, the following was performed: 1) dichlorofluorescein (DCF) assay to evaluate reduction in LEC reactive oxygen species (ROS) production; 2) a protein array to determine changes in cytokine expression; 3) an MTT assay to evaluate the antioxidants effects on LEC viability; 4) a scratch wound assay to evaluate LEC migration and proliferation; 5) an ex vivo model of posterior capsular opacification (PCO) to evaluate LEC migration and proliferation. GSE’s antioxidant reductive effects surpassed the positive control, while lutein and O3FA showed little reductive ability. The DCF assay corroborated this data; GSE reduced ROS production in LECs compared to positive controls. Lutein was pro-oxidative and O3FA had negligible effects on ROS production. GSE decreased IL-6, IL-8, CCL3, and CCL5 expression compared to controls. Lutein and O3FA showed increased or similar cytokine expression compared to controls. All tested antioxidants decreased in vitro LEC viability compared to controls. All tested antioxidants also decreased LEC migration in the scratch wound assay with presumed toxic effects on the cells. Ex vivo PCO was increased following treatment with O3FA, while GSE and lutein treatments were similar to controls. In conclusion, only GSE showed substantial antioxidant capabilities and reduced ROS generation. Lutein and O3FA demonstrated no antioxidant abilities and lutein proved pro-oxidative in vitro. Following antioxidant treatment, LECs showed altered expression of cytokines influencing redox signaling, migration, and proliferation. O3FA increased cell proliferation and migration in an ex vivo PCO model while GSE and lutein demonstrated little effect. Careful conclusions should be made regarding the effects of the studied antioxidants on LECs due to findings of variable and limited reducing power.

Committee:

Heather Chandler, PhD (Advisor); Anne Gemensky-Metzler, MS, DVM, DACVO (Advisor); David Wilkie, MS, DVM, DACVO (Committee Member)

Subjects:

Medicine

Keywords:

Antioxidants; Lens Epithelial Cells; Posterior Capsular Opacification

Grant, Edwin ArthurImmuno-Labeling of Yes-associated Protein in the Crystalline Lens
Master of Science, The Ohio State University, 2016, Vision Science
Purpose: Yes-associated protein (YAP) is a transcriptional co-activator responsible for increasing cellular proliferation in multicellular tissues. YAP activity has been linked to many physiological changes throughout the body and is hypothesized to play a role in crystalline lens physiology and in cataractogenesis. Cataracts and secondary cataracts (posterior capsular opacification that occurs after cataract surgery) are the leading causes of blindness worldwide and pose major social and health related problems. A better understanding of cataractogenesis could lead to the development of novel strategies to prevent cataracts and the improvement of cataract surgical outcomes. This research aimed to develop a protocol for immunostaining YAP within the canine crystalline lens, with a long-term goal to better understand the role YAP plays in the lens in health and pathology. Methods: Starting from a standard immunohistochemical (IHC) protocol, the following steps were evaluated and optimized: antigen retrieval, antibody selection, antibody concentration, tissue blocking, tissue fixation, and tissue mounting. Furthermore a protocol for immunofluorescence (IF) was optimized in addition to further evaluations on tissue mounting and fixation. Results: Several IHC protocols tested were found to produce positive staining of YAP proteins in situ. Predominantly, cytoplasmic expression of YAP was noted in the equatorial cells within the transition zone for lens fiber differentiation in IHC experiments. Use of IF techniques in cultured lens epithelial cells (LEC) also produced positive staining for YAP. Immunoreactivity was both cytoplasmic and nuclear in cultured LEC in IF protocols; though the majority was cytoplasmic, some nuclear immunopositivity was apparent within cells that were less confluent. Western blots confirmed antibody specificity. Conclusions: This research demonstrates that YAP proteins can be evaluated within the canine lens via IHC and IF methods, as well as western blotting. Staining patterns observed in this study suggests YAP activity in normal lens physiology, such as fiber cell differentiation. The methods developed in this research can subsequently be used to compare YAP expression and function in health and pathophysiology, with a goal of developing methods to delay cataractogenesis.

Committee:

Heather Chandler, PhD (Advisor); Andrew Hartwick, OD, PhD (Committee Member); Timothy Plageman, PhD (Committee Member)

Subjects:

Anatomy and Physiology; Biology; Immunology; Medicine; Ophthalmology

Keywords:

Immunohistochemistry; Immunofluorescence; Yes-Associated Protein; YAP; Crystalline Lens;

Eckes, MelissaShroom3 Localization and Apical Constriction during the Development of the Crystalline Lens in Mouse Embryos
Master of Science, The Ohio State University, 2017, Vision Science
Purpose: The purpose of this research was to analyze the localization of the protein Shroom3, and determine its role in regulating lens fiber cell shape during the organization and development of the embryonic lens. It has previously been shown in the lens placode that Shroom3 is a crucial component in the pathway that leads to apical constriction. To determine if this is also the case in the lens fiber cells within the lens bow of developing lenses, the localization of Shroom3 expression was first evaluated, followed by an analysis of the degree of apical constriction. Methods: Control and Shroom3-deficient mouse embryos were dissected, cryosectioned through the developing lens, and imaged. The images were analyzed following histological labeling using the x-gal assay, and immunofluorescent labeling of specific proteins including Shroom3, beta-catenin, non-muscle myosin IIb and F-actin. Results: Shroom3 mRNA expression is localized to the cells within the lens epithelium, and the lens fiber cells in contact with the lens fulcrum, but not in older, more centrally located lens fibers. Antibody staining showed Shroom3 protein localization within the membranes of these same cells. This stands in contrast to the more specific apical localization observed in other epithelial tissues. As the cells were differentiating, they changed from a columnar-shaped cell to a conical-shaped cell. F-actin and non-muscle myosin expression was diminished apically and increased basally in the Shroom3 null mice embryos. Differentiating lens fiber cells at the lens fulcrum apically constricted less in the Shroom3 null mouse embryos than the controls. Conclusion: Shroom3 directs apical constriction of lens cells as they differentiate from lens epithelial cells to lens fibers in part by modulating the distribution of F-actin and non-muscle myosin.

Committee:

Timothy Plageman (Advisor); Heather Chandler (Committee Member); Andrew Hartwick (Committee Member)

Subjects:

Developmental Biology

Keywords:

Shroom3 protein; Crystalline Lens development; mouse embryos

Carter, Kristina A.Nutrient-Specific System v. Full Fact Panel: Understanding Nutritional Judgment Using Lens Model Analysis
Master of Science (MS), Ohio University, 2017, Experimental Psychology (Arts and Sciences)
Current food labels include comprehensive nutritional information, but evaluations of their effects on judgments of nutritional quality and food choice are scarce. Building on previous empirical research that demonstrates that amount and complexity of information is negatively related to judgment accuracy, this study used an experimental design to evaluate nutritional information labels of varying complexity. Lens model analysis (Brunswik, 1955; Cooksey, 1996; Hammond, 1955; Stewart, 1976) was used to quantitatively compare individuals’ judgment accuracy to a gold standard nutritional quality criterion in three conditions that implemented front-of package (FOP) labels. The conditions were: no highlighted information, information highly related to nutritional quality highlighted, and information marginally related to nutritional quality highlighted. Findings indicate that different FOP labels had different effects on accuracy, but there were no effects of FOP labeling on judgment consistency, model agreement, or nutritional choice. Implications for understanding efforts to improve American food choices and reducing obesity are discussed.

Committee:

Claudia González-Vallejo (Committee Chair); Jeffrey Vancouver (Committee Member); Sarah Racine (Committee Member)

Subjects:

Psychology

Keywords:

judgment and decision making; labeling; information; lens model analysis; front of package; nutrition fact panel; NFP; judgment accuracy; cue use

Meniru, Maryann OThe Influence of Degree of Afroncentric Spirituality on Psychological Help Seeking Attitudes, Intentions and Stigma among Nigerian Americans
Doctor of Philosophy, University of Akron, 2013, Counselor Education and Supervision
The study examined the relation between Afrocentric Spirituality and psychological help seeking attitudes, intentions, and stigma among Nigerian Americans. The researcher investigated whether stronger Afrocentric Spirituality was associated with weaker attitudes toward seeking psychological help, less intention to seek mental health services, and stronger self and other perceived stigma toward psychological help seeking. The sample included 122 adult first generation Nigerian Americans from three different states in the South and Midwest. Participants completed a demographic questionnaire, the Spirituality Scale (Jagers & Smith, 1996), the Perception of Stigmatization by Others for Seeking Psychological Help Scale (Vogel et al., 2009), the Self-Stigma of Seeking Help (Vogel et al., 2006), the Intention to Seek Counseling Inventory (Cash, Begley, McCown, & Weise, 1975), and the Attitudes Toward Seeking Professional Psychological Help Scale-Short Form (Fischer & Turner, 1970). Results from a multiple regression analysis indicated that there was no relation between Afrocentric Spirituality and help- seeking attitudes or self stigma about seeking mental health services. There was a positive correlation between Afrocentric Spirituality and other stigma, demonstrating that as Afrocentric Spirituality increased the perception of others&#x2019; stigma (i.e., friends, relatives) about seeking mental health services also increased. Contrary to expectations, there was a positive correlation between Afrocentric Spirituality and intentions to seek psychological help, indicating that as Afrocentric Spirituality increased participants had a iv stronger intention to seek mental health services for certain concerns. Follow-up analyses were utilized to determine whether sample demographic characteristics (e.g., level of education, socioeconomic status, income, and age immigrated to the United States) were related to Afrocentric Spirituality or help-seeking intentions. However, non-significant results were obtained. Implications for counseling practice, theory, and counselor education were presented, as were recommendations for future research

Committee:

Robert Schwartz, Dr. (Advisor); Cynthia Reynolds, Dr. (Committee Member); Sharon Kruse, Dr. (Committee Member); John Queener, Dr. (Committee Member); Varunee Faii Sangganjanavanich, Dr. (Committee Member)

Subjects:

Counseling Education

Keywords:

Afrocentric Spirituality, Psychological help seeking, Stigma, Mental health practices, Nigerian Americans, Culture, Diunital Reasoning, Help seeking attitudes, Intentions, Eurocentric lens, Counselor Education and Supervision, CACREP,

Jain, AnuragExperimental study and numerical analysis of compression molding process for manufacturing precision aspherical glass lenses
Doctor of Philosophy, The Ohio State University, 2006, Industrial and Systems Engineering
Compression molding has emerged as a promising technology for manufacturing aspherical glass lenses. In this method a glass gob or blank is pressed in a single operation into the shape of a finished lens. Annealing of the formed lens is then performed to achieve optical quality. The process is net shape, environment friendly and suitable for high volume production but has some inherent limitations which have prevented it from being used for industrial lens production. This dissertation research seeks a fundamental understanding of the molding process by adopting a combined experimental, analytical and numerical Finite Element Method (FEM) approach. Preliminary experiments were performed involving molding of a test aspherical glass lens on a commercial machine to study process capability to manufacture an optic component within the desired specifications. Experiments were also performed to determine the effect of different molding parameters on the final molded lens quality. A compression molding machine was designed and built in the laboratory. High temperature elastic modulus measurements were performed using Brillouin light scattering technique. The measured glass properties were used as input to the numerical simulation of cylinder compression experiments and lens molding. A numerical FEM simulation model of lens molding was developed and predictions were compared with the experiments. A 1D analytical heat transfer model during lens annealing has been presented that takes into account transient heat transfer at the glass-mold boundary. The possibility of implementing molding to make microlens array, freeform lens and diffractive lens has also been demonstrated. Experimental results have showed that molding process is capable of producing precision glass lenses with shape and form accuracy comparable to lenses manufactured using conventional abrasive techniques. Within the range investigated, the experiments did not show a significant influence of the molding parameters on the final lens quality. The predicted lens curve shape results were in good agreement with the experimental measurements. Additionally, numerical simulation was able to predict, residual stress in the glass lens as a function of process parameters which shows that FEM can possibly be used to predict, optimize and improve the performance of a lens molding process.

Committee:

Allen Yi (Advisor)

Keywords:

molding; aspherical lens; glass; viscosity; stress relaxation; structural relaxation; high temperature; numerical simulation; modeling; manufacturing

LI, WEIXINA HYBRID DEVICE APPROACH TO HIGH PERFORMANCE IN ORGANIC LIGHT-EMITTING DIODES
PhD, University of Cincinnati, 2006, Engineering : Electrical Engineering
Hybrid device approaches have been utilized in this research to study the Alq3-based [tris-(8-hydroxyquinoline) aluminum] organic light emitting diode (OLED) structures and europium complex doping in OLEDs. Bright, efficient Alq3-based hybrid polymer/small-molecule (OLED) structures that incorporate hemispherical lenses for increased output power efficiency were engineered. The 6-layer hybrid OLED structure contains 2 spin-coated polymer layers and 4 thermally evaporated small molecule layers. This structure results in balanced charge injection, thus leading to a bright and efficient device. The use of index-matched transparent lenses resulted in luminous and external quantum efficiency of 7.5 lm/W and 8%, respectively. Hybrid electroluminescent/photoluminescent device structure were also fabricated, in which high quantum yield (>90%) lumophores were incorporated with the conventional OLED structure as a color conversion material (CCM) to achieve high efficient devices in various colors. Saturated yellow, orange and red devices with external quantum efficiencies as high ~4% were obtained by using CCM lensed approach. Two Eu complexes, Eu(Brittany) and Eu(Pigment) were evaporated under ultra high vacuum to incorporate into OLED structure as emitting centers. Electroluminescence from Eu3+ was obtained for both Eu complexes with dominant emission peak of 612 nm as a result of 5D0-7F2 transition. A voltage-induced red to blue color tunable device was demonstrated by using a coevaporated emissive layer of NPB [(N,N’-bis(naphthalene-1-yl)-N,N’-bis(phenyl)benzidine)] and Eu(pigment) complex. As a result of a minimized energy transfer from the blue emitter (NPB) to the red emitter (europium complex), the hybrid molecular/atomic (NPB/Eu3+) lumophores are able to yield chromaticity coordinates range with increasing applied bias of CIEx = 0.61-0.17 and CIEy = 0.31-0.12, respectively.

Committee:

Dr. Andrew Steckl (Advisor)

Keywords:

OLED; Alq3; europium complex; color tunable; outcoupling; color conversion; lens

Collins, Peter ChancellorA combinatorial approach to the development of composition-microstructure-property relationships in titanium alloys using directed laser deposition
Doctor of Philosophy, The Ohio State University, 2004, Materials Science and Engineering
The Laser Engineered Net Shaping (LENS™) system, a type of directed laser manufacturing, has been used to create compositionally graded materials. Using elemental blends, it is possible to quickly vary composition, thus allowing fundamental aspects of phase transformations and microstructural development for particular alloy systems to be explored. In this work, it is shown that the use of elemental blends has been refined, such that bulk homogeneous specimens can be produced. When tested, the mechanical properties are equivalent to conventionally prepared specimens. Additionally, when elemental blends are used in LENS™ process, it is possible to deposit compositionally graded materials. In addition to the increase in design flexibility that such compositionally graded, net shape, unitized structures offer, they also afford the capability to rapidly explore composition-microstructure-property relationships in a variety of alloy systems. This research effort focuses on the titanium alloy system. Several composition gradients based on different classes of alloys (designated a, a+b, and b alloys) have been produced with the LENS™. Once deposited, such composition gradients have been exploited in two ways. Firstly, binary gradients (based on the Ti-xV and Ti-xMo systems) have been heat treated, allowing the relationships between thermal histories and microstructural features (i.e. phase composition and volume fraction) to be explored. Neural networks have been used to aid in the interpretation of strengthening mechanisms in these binary titanium alloy systems. Secondly, digitized steps in composition have been achieved in the Ti-xAl-yV system. Thus, alloy compositions in the neighborhood of Ti-6Al-4V, the most widely used titanium alloy, have been explored. The results of this have allowed for the investigation of composition-microstructure-property relationships in Ti-6-4 based systems.

Committee:

Hamish Fraser (Advisor)

Subjects:

Engineering, Materials Science

Keywords:

combinatorial method; combinatorial approach; laser deposition; directed laser deposition; LENS; titanium; molybdenum; Ti-6-4; Ti-6Al-4V; Timetal 21S; composition; microstructure; property; relationships; neural network; fuzzy logic

Bhavani, Madakashira P.THE ROLE OF FRS2α IN LENS DEVELOPMENT
Doctor of Philosophy, Miami University, 2012, Zoology
For more than a century, the lens has provided an excellent model to elucidate the basic processes of induction, differentiation, cell cycle exit and cell survival mechanisms. The lens is composed of a single layer of proliferative epithelial cells in the anterior hemisphere and the bulk of the lens is composed of post- mitotic fiber cells that are continually differentiated from the epithelial cells at the lens equator. Lens epithelial cells express numerous receptor tyrosine kinases with the ability to initiate cell signaling ultimately leading to the phosphorylation (activation) of Erk1/2 and PI3-K/Akt signaling. However, only the over- expression of Fgfs in the lens leads to premature fiber cell differentiation of the epithelial cells in transgenic mice (characterized by expression of β crystallins), and the lens specific loss of Fgfrs lead to abrogation of fiber cell differentiation, and extensive cell death. A variety of signaling proteins are phosphorylated in response to Fgf stimulation, including Shc, phospholipase-Cγ, STAT1, Gab1 and docking molecules Frs2α and Frs2β. We have shown that Frs2β is not expressed in the murine lens, and within the lens, only Fgfrs tyrosine phosphorylate and activate Frs2α. In mice, the lens specific loss of Frs2α significantly increases apoptosis and decreases phosphorylation of both Erk1/2 and Akt, decreases cell survival, fiber cell elongation and fiber cell differentiation. Although not normally expressed in the lens, the receptor TrkC tyrosine phosphorylates Frs2α upon stimulation by NT3. Transgenic mice expressing TrkC and NT3 in the lens exhibit increased Erk1/2 and Akt activation as well as the elongation and the expression of β-crystallins in the lens epithelium that remains entirely dependent on Frs2α activation.

Committee:

Michael Robinson, L (Advisor); Katia Del Rio-Tsonis (Committee Member); Paul James, F (Committee Member); Paul Harding, A (Committee Member); Michael Crowder, W (Committee Chair)

Subjects:

Developmental Biology; Genetics; Molecular Biology

Keywords:

ocular lens; Frs2&945;; development; mouse genetics

Prabhu, Avinash WImproving Fatigue Life of LENS Deposited Ti-6Al-4V through Microstructure and Process Control
Master of Science, The Ohio State University, 2014, Welding Engineering
Laser Engineered Net Shaping (LENS) is a solid freeform fabrication process capable of producing net shape, custom parts through a layer-by-layer deposition of material using a laser energy source. LENS based Ti-6Al-4V parts are currently being explored for applications to aerospace and biomedical implant applications. To achieve satisfactory mechanical performance in the components, homogeneity of the microstructure and the physical structure is important. This study explores methods of improving the fatigue life of Ti-6Al-4V LENS deposits through the creation of defect free components with appropriate microstructure. The work focuses on the impact of beta grain refinement and the elimination of lack of fusion porosity defects on the fatigue life of the alloy. Further, a model is developed to predict the epitaxial grain growth in LENS builds of Ti-64. This model is used to augment the prediction capability of a simultaneous transformation kinetics (STK theory) based model developed previously. The beta grain refinement in the fatigue properties of Ti-64 is achieved through addition of boron in amounts < 3 wt%. The addition of boron is found to refine the columnar beta structure typically observed in LENS deposited Ti-64. However, at high concentrations of boron, it was difficult to discern the prior beta grain size to visualize the extent of grain refinement. The boron alloying further causes a significant change in the structure of alpha laths, leading the shorter and thicker individual laths. Grain boundary alpha is not observed in the microstructure on addition of boron above a certain threshold. The addition of boron is observed to improve the fatigue properties of deposited Ti-64 samples. The Ti-64 LENS builds are observed to contain lack-of-fusion porosity in the lower regions of the deposit close to the substrate. The effect of process parameters namely the power, travel speed, hatch width, pre-heating, powder flow rate, substrate surface quality, and the hatch path on the amount of porosity is analyzed through trial experiments followed by a more detailed design of experiments approach. At a fixed power setting of 400W, the hatch width and powder flow rate are observed to have a significant influence on the extent of porosity present in the deposit. The hatch width has been further optimized through a CFD based simulation based approach leading to an increased material efficiency and reduced time of building. These builds are observed to show a columnar beta grain structure growing epitaxially from the base of the deposit and consist of primarily basketweave alpha. The fatigue properties are analyzed at the combination of parameters determined through experiments and are found to show an improvement over previously reported values by 3 times. The epitaxial grain growth seen in the LENS deposits is modeled using the classical grain growth equation. The prediction is observed to be sensitive to the atomic mobility, starting grain size, activation energy for grain growth and alpha dissolution temperatures. This grain growth information is incorporated into simultaneous transformation kinetics (STK theory) based microstructure model to improve the predictions of microstructure fraction in Ti-6Al-4V LENS builds.

Committee:

Wei Zhang (Advisor); Dave Farson (Committee Member); Sudarsanam Babu (Committee Member)

Subjects:

Materials Science

Keywords:

Ti-6Al-4V; LENS; Additive Manufacturing; Laser Additive Manufacturing; Grain growth modeling; Boron alloyed Ti-6Al-4V;

Chandler, Heather LynnEpithelial-mesenchymal transition in the anterior segment of the eye
Doctor of Philosophy, The Ohio State University, 2006, Veterinary Biosciences

Epithelial-mesenchymal transition (EMT) occurs as part of development, tissue repair, and tumor progression. Complete EMT is characterized by transformation of closely associated immobile epithelial cells into individual motile fibroblast-like cells. This phenotypic change is characterized by disruption of all cell-cell junctions and increased protease production. EMT is stimulated by growth factors, and in all cases thus far studied, EMT appears to be controlled by transcription factors belonging to the Snail family.

We demonstrate that Slug is required for corneal epithelial cell migration from murine corneal explants in vitro, and confirm the importance of Slug during EMT in the cornea by demonstrating the strong association between Slug expression and successful corneal wound healing in canine eyes in vivo. Slug is transiently expressed at the margins of healing corneal wounds and decreased Slug expression at corneal wound margins is accompanied by failure of EMT in non-healing corneal erosions of dogs. Finally, enhanced expression of Slug in corneal explants due to adenoviral transfection or tetracycline treatment increases the rate of epithelial cell migration.

UVR exposure of the cornea leads to increased expression of markers of EMT, including Snail and Slug and MMPs. Canine chronic superficial keratitis (CSK) is an inflammatory disease associated with UVR exposure. Our findings suggest that overexpression of MMPs due to UVR exposure may be linked to changes in the cornea during CSK that allow an influx of inflammatory cells and neovascularization.

We also demonstrate that EMT occurs in lens epithelial cells (LEC) during the repopulation of the lens capsule following cataract surgery with the subsequent development of posterior capsular opacification (PCO). In addition, there is increased expression of cyclooxygenase-2 (COX-2) in clinical samples of canine cataracts and PCO. Inhibiting the enzymatic activity of COX-2 effectively prevented EMT of LEC in our ex vivo model of PCO.

The findings reported here demonstrate that partial EMT occurs in a variety of situations in differentiated epithelial cells of the adult anterior eye. Understanding the molecular events that initiate partial EMT in CEC and LEC will provide important insights into the pathology of ocular diseases and ways to control the process.

Committee:

Donna Kusewitt (Advisor)

Keywords:

EMT; Slug; Cornea; Lens

SONG, NIGENETIC ANALYSIS OF EARLY LENS DEVELOPMENT IN MOUSE
PhD, University of Cincinnati, 2007, Medicine : Molecular and Developmental Biology
DrosophilaPygopus was originally identified as a core component of the canonical Wnt signaling pathway and a transcriptional coactivator. Here we have investigated the microophthalmia that arises in mice with a germ-line null mutation of Pygopus2. We show that this phenotype is a consequence of defective lens development at inductive stages. Using a series of regionally limited cre recombinase transgenes for conditional deletion of Pygopus2 floxwe show that Pygopus2 activity in pre-placodal presumptive lens ectoderm, placodal ectoderm and ocular mesenchyme all contribute to lens development. In each case Pygopus2 is required for normal expression levels of the critical transcription factor Pax6. Finally, we provide multiple lines of evidence that although Pygopus2 can function in the Wnt pathway its activity in lens development is Wnt pathway-independent.

Committee:

Dr. Richard Lang (Advisor)

Subjects:

Biology, Molecular

Keywords:

Pygopus2; mouse; lens development; neural crest derived mesenchyme; Pax6; Wnt pathway

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