Master of Fine Arts, The Ohio State University, 2006, Graduate School

Committee: Not Provided (Other) Subjects:

Doctor of Philosophy, The Ohio State University, 2024, EDU Teaching and Learning

This qualitative research study sought to uncover the benefits of an employer-tailored training intervention in addressing employer knowledge, perspectives, and attitudes regarding employing an individual with a visual impairment, with the ultimate goal of identifying a way to positively impact the high unemployment rate amongst this population. This study continues to address necessary employment barrier research needed within the field of education and rehabilitation of the visually impaired. Data gathering was obtained in three phases, through (1) pre- and post-survey questionnaires, with both closed and open-ended survey questions, and (2) fieldnotes collected during the training intervention. Data was analyzed through a constant comparison grounded theory model using cross-references between fieldnotes and pre- and post-survey data. Quantitative data collected regarding survey responses from the Employer Perspectives on the Employment of People with Disabilities through the Office of Visual Impairment and Employment Policy, U.S. Department of Labor (Domzal, Houtenville, & Sharma, 2008) was used to provide supportive descriptive statistics only due to low participant response rates. These responses showed some positive changes within select categories. Positive changes included the understanding that individuals with visual impairments could operate a smart phone, access email, and independently operate a PC or laptop. Additionally, respondents agreed their company could afford to accommodate an individual with a visual impairment and could benefit from disability awareness training to increase overall knowledge, confidence in hiring, willingness to hire, and dispel concerns regarding employing an individual with a visual impairment. Qualitative open-ended pre and post-survey data indicated increased knowledge in the areas of (a) accommodations and assistive technology, (b) state vocational rehabilitation programming (e.g. job coach support, funding, training (open full item for complete abstract)

Committee: Danene Fast (Committee Member); Tiffany Wild (Advisor) Subjects: Adult Education; Special Education; Vocational Education

Doctor of Philosophy, The Ohio State University, 2023, EDU Teaching and Learning

Abstract This research attempted to begin to examine the problem of why youth and consequently, adults with complex disabilities, are not being employed in competitive, integrated environments. As policy, WIOA mandates this status with few exceptions. The study asked, “who and/or what state, and local agencies provide services that mean to support employment and community access?” The study also questioned what services are successful in providing employment supports to consumers with complex disabilities, as well as the barriers to providing supports. The study used a theoretical framework that combined a Stages-Heuristic policy model and Organizational Niche Theory in which to view the problem. A qualitative research design was used along with descriptive statistics of an electronic survey sent to 123 VR, DD agency and Blind/VI services personnel. A Focus Group was facilitated to expand on survey responses and help discover or add to emerging themes from open- ended survey questions. The results of the survey were limited, with only 17 participants responding to questions. The Focus Group with three members, was also limited in geographical regions, as well as representative agencies. Therefore, it was impossible to answer the main questions regarding what state agencies provide specialized services to individuals with complex disabilities for the purpose of competitive, integrated employment. However, the open-ended questions/responses gave good insight into what services are provided, which are successful, and what barriers the responding agencies have in providing specialized services. The Focus Group discussion added to the survey responses, and several themes were apparent. The responses also reinforced much of the current literature (of which there is little) around employment attainment for individuals with significant disabilities.

Committee: Tiffany Wild PhD (Advisor) Subjects: Education; Public Policy; Special Education

Doctor of Psychology (Psy.D.), Xavier University, 2023, Psychology

Racial disparities among adults and juveniles pervade the current US (retributive) justice system, with White and younger offenders often getting more lenient treatment. Very little research has explored the possibility that Restorative Justice (RJ) practices may be subject to the same biases. The current study explored how opinions about RJ were impacted by the offender's racial identity, the offender's age, and factors associated with respondent's identification with the offender. Participants (N=225) were randomly assigned to 1 of 6 survey vignettes. Each depicted the same road rage incident but varied the race (African American, European American, Hispanic) and age (17 years old/35 years old) and accompanying mugshot photo. Participants rated the appropriateness of seven potential consequences, which included retributive justice and RJ practices. Contrary to predictions, no significant differences in consequence severity appropriateness ratings emerged across offender race, age, or their interaction. Overall, participants rated RJ outcomes as significantly more appropriate for all offenders than retributive justice outcomes. However, results indicated that participants' who reported higher racial bias rated more severe consequences as more appropriate for African American offenders and LatinX offenders but did not show this pattern for European American offenders. Racial bias showed significant positive associations with identifying as non-White (r = .37) and with political conservatism (r = .28). The findings suggest that RJ practices are viewed positively by most individuals and as equally appropriate for all offenders.

Committee: Susan Kenford Ph.D. (Committee Chair); Kathleen Hart Ph.D., ABPP (Committee Member); Jennifer Gibson Ph.D. (Committee Member) Subjects: African Americans; Criminology; Hispanic Americans; Psychology

Master of Education (MEd), Bowling Green State University, 1966, Psychology

Committee: Darrel G. Minifie (Advisor) Subjects: Psychology

Ph.D., Antioch University, 2022, Leadership and Change

Companies have increasingly turned to text-based communications to recruit, hire, and manage a distributed remote workforce. For people who are blind or visually impaired, this movement presents both challenges and opportunities for attaining and retaining employment. Does the potential isolation of telework have a negative effect on workplace relationships for people who are blind or visually impaired? Does participation in text-based workspaces mitigate stereotypes and stigmatization experienced by people with visible disabilities? Using a constructivist grounded theory framework, this study explored how people who are blind or visually impaired experience relationships in text-based workspaces. Building and maintaining social connections and networks is critical for employment success, so understanding the factors at play in text-based workplace communications is key. Interviews with 18 blind or visually impaired professionals revealed a number of ways individuals connected with colleagues, cultivated professional identity, and built extended networks. This happened despite challenges from technologies and organizational processes that failed to account for employees who are visually impaired. This investigation resulted in the development of an emergent theory and a model that can advance policies and practices for employers and for employment training and support programs. This dissertation is available in open access at AURA (https://aura.antioch.edu/) and OhioLINK ETD Center (https://etd.ohiolink.edu/).

Committee: Mitchell Kusy PhD (Committee Chair); Harriet Schwartz PhD (Committee Member); Bonnie O'Day PhD (Committee Member) Subjects: Behavioral Psychology; Business Administration; Communication; Information Systems

Doctor of Philosophy (PhD), Ohio University, 2022, Counselor Education (Education)

The goal of this research is to identify factors predicting suicide foreseeability skills of vocational rehabilitation counselors (VRCs) working with individuals who have a visual impairment with a secondary mental health disorder. Suicide attempts are a problem with rates on the rise for individuals who are visually impaired with a mental health disorder (Meyer-Rochow et al., 2015). VRCs have many responsibilities which requires these professionals, who are trained as counselors, to focus less on clinical symptoms and more on work-focused outcomes. This study included a total of 79 VRCs, and predicted whether three primary predictor variables, counselor self-efficacy, perceived preparedness to work with clients who are suicidal, as well as managing countertransference skills, predicted the suicide foreseeability skills of VRCs working with clients with a visual impairment and mental health disorder. This research is unique as it looked specifically at VRCs, as much of the previous research on this topic focused on foreseeability skills of only mental health counselors, psychiatrists, social workers or psychologists. The participants of this research were between the ages of 20-70 years of age. Neither of the three predictors, or demographic variables, were found to be significant linear predictors of suicide foreseeability skills of VRCs in this research. However, there was a significant finding of a curvilinear quadratic relationship of perceived preparedness as a predictor of foreseeability skills of VRCs. In other words, 4 moderate levels of counselor anxiety and counselor confidence (perceived preparedness) was a significant predictor of suicide foreseeability skills of VRCs. This means VRCs who maintain moderate anxiety, who are not overly confident in their abilities, perform their best with clients who may be experiencing a short-term, active period of suicidal crisis. This moderate level of perceived preparedness was found to be pred (open full item for complete abstract)

Committee: Bilal Urkmez (Committee Chair); Yuchun Zhou (Committee Member); Christine Bhat (Committee Member); Adrienne Erby (Committee Member) Subjects: Counseling Education

PHD, Kent State University, 2021, College of Arts and Sciences / Department of English

The field of Disability Studies (DS) generally avoids addressing the problem of suffering and disability due to the long history of harmful stereotyping of disability as being a bad state of existence. When suffering is addressed, it tends to be conceptualized and criticized as a consequence of social oppression; and, as such, the experience is devalued. Some DS theorists have attempted to analyze the problem of impairment-derived suffering, but they tend to narrowly focus on experiences of physical pain and avoid the negative psychological effects of lacking physical abilities. The problem of suffering and its value is a central concern for the philosopher Friedrich Nietzsche (1844-1900). Many of his works explore the experience of suffering and the psychological need for suffering to have meaning in a world that no longer offers convincing metaphysical justifications for it. Nietzsche argues that suffering has value and is necessary for human flourishing; and, in opposition to philosophical pessimists like Arthur Schopenhauer, he asserts that suffering must be affirmed. This Nietzschean perspective on suffering has vital implications for conceptualizing and interpreting negative experiences involving disability in general, and blindness specifically. In Part 1, I describe several DS interpretations of suffering, and compare/contrast them with Nietzsche's interpretation. In Part 2, I use these interpretations to analyze experiences of blindness and suffering in memoirs and tragic literature. I ultimately argue that, if blind people are to flourish, we must adopt a Nietzschean interpretation of suffering. This interpretation requires us to affirm the value of suffering in blindness and to reject interpretations, such as social oppression, that devalue suffering.

Committee: Sara Newman (Advisor) Subjects: Literature; Philosophy

Ph.D., Antioch University, 2020, Leadership and Change

This thesis explored social worker discourses to learn what they could reveal about professional workplace practices and experiences with race and racism. The study traced the subtle and elusive racism often found in everyday professional conversations that are not considered racist by dominant consensus. Using tools of thematic and critical discourse analysis (CDA), and van Dijk's (1993, 2001, 2008, 2009, 2011) general theory of racism and denial (1992, 2008), data from 14 semistructured interviews and one focus group with a racially diverse group of social workers was analyzed in two ways. First, thematic analysis offered a horizontal or flat exploration that illustrated various manifestations of racism, denial, and whiteness. The second, vertical critical discourse analysis took a sociocognitive approach to examine underlying discourse structures that hold racism and whiteness in place. Findings suggest the presence of subtle and nuanced racism and whiteness in social worker discourses, and I discuss how these forces work in tandem to produce dynamics that preserve hegemonic structures and support dominant status. This power analyses brought attention to often overlooked forms of counter-power and resistance embedded in participant narratives. Inferences from focus group discourse illustrated four interpersonal capacities that supported constructive racial dialogue. Findings revealed vastly different racial experiences between Black, biracial, and White social workers in their professional settings. Implications for social work (and more broadly the helping professions) education, training, and leadership and change practices are provided. This dissertation is available in open access at AURA: Antioch University Repository and Archive, http://aura.antioch.edu/ and OhioLINK ETD Center, https://etd.ohiolink.edu/

Committee: Philomena Essed PhD (Committee Chair); Donna Ladkin PhD (Committee Member); Donna Jeffery PhD (Committee Member) Subjects: Communication; Minority and Ethnic Groups; Multicultural Education; Social Research; Social Work

Doctor of Philosophy, The Ohio State University, 2020, English

Pathology and Pity traces the interdependence of medical and moral models of disability in American literature of the long nineteenth-century, from Royall Tyler's The Algerine Captive (1797), to several short stories by Edgar Allan Poe in the 1840s, to the promotional materials of stuttering school literature from the 1880s to the 1920s, to Herman Melville's Billy Budd, unpublished at the time of Melville's death but composed 1888-1891. The interdependence of these models shapes not just the way that disability is represented in the works examined, but also the way that disability functions in and shapes the narratives. Each chapter focuses on how medical and moral discourses related to a particular disability - blindness, madness, and stuttering - in contemporaneous philosophical, medical, journalistic, and promotional writings influenced the literary works examined. Throughout nineteenth-century America, the relationship between medical and moral models of disability produced a number of related discourses that tie into Foucault's concepts of disciplinary power and biopower: compulsory ablebodiedness; disability as an object of and barrier to sympathy; the push toward cure; the ability of diagnosis to reliably read pathological and moral defects; the connection between willpower, self-awareness, and ability; the benevolence of medicine; and the elevation of expertise. Some works of American nineteenth-century literature reinforce these discourses, others challenge them, and some exhibit a tension between the two positions. Disability functions as a narrative device to speak to national debates in American culture and to comment on the very nature of storytelling and reading. Tyler's novel uses the cure of blindness to reflect on the proper way of seeing America and telling the story of becoming a proper American citizen. Poe's stories incorporate anxieties about madness and psychiatric diagnosis to address concerns about criminal responsibility and the role of (open full item for complete abstract)

Committee: Amy Shuman (Advisor); Molly Farrell (Committee Member); Elizabeth Renker (Committee Member) Subjects: American History; American Literature; American Studies; Epistemology; Ethics; History; Literature; Medical Ethics; Science History

Ph.D., Antioch University, 2019, Antioch New England: Marriage and Family Therapy

In this dissertation, I seek to understand the factors that play a role in the success of African American Scholars in the Marriage and Family Therapy field, by conducting an extensive literature review of factors that may affect matriculation and retention through lived experiences. In the study, I use narrative inquiry, research questions and Husserlian Phenomenological methodology to explore the challenges important to the African American journeys toward success. In the first chapter, I introduced the criteria in which the study focused which highlighted four areas of accomplishments including clinical, teaching, supervision, and research. dissertation that follows. The second chapter presents a critical review of the literature, discussing factors of theoretical orientation, critical race theory and the five tenets that are essential factors within the study. In the third chapter, I discuss the biography of each African American scholar as it relates to the underlined accomplishments overtime including, research, publications, teaching and therapy. Chapter four describes the methodology used to determine the impact of the experiences and how they were interpreted as results. In Chapter five, I discuss the results and common themes found within the African American scholar experiences. Finally, in Chapter six I summarize the results in its entirety and discuss the studies overall impact on the field of Marriage and Family Therapy. Moreover, I discuss the limitations, and future research directions.

Committee: Kevin Lyness PhD (Committee Chair); Walter Lowe PhD (Committee Member); Nicholas Jordan PhD (Committee Member) Subjects: African Americans; Therapy

Master of Sciences, Case Western Reserve University, 2018, Clinical Research

Background: Vision impairment (VI) and cataract are common causes of disability in U.S. adults age 65 and older, but are especially, highly prevalent in institutionalized elderly. Objective: To estimate prevalence of VI and cataract in both populations and compare prevalence trends since 1985. Method: A meta-analysis included studies containing both nursing home and community elderly populations. A secondary (synthetic) meta-analysis also included studies containing only one of the two populations, pooled by 10-year cohorts. Results: The meta-analytic pooled prevalence estimates for VI and cataract in nursing home elderly are .50 and .48. In community elderly, these estimates are .04 and .17 respectively. Both meta-analyses indicate significantly higher odds (p<.001) of VI in nursing home elderly (OR1=26.123, OR2=31.097) and cataract (OR1=8.868, OR2=6.378). VI trends in both groups are remaining stable. While community studies are showing a rise in cataract prevalence, nursing home studies indicate a declining trend since mid-1990's.

Committee: Sara Debanne PhD (Advisor); Douglas Rowland PhD (Committee Member); James Spilsbury PhD (Committee Member); Jonathan Lass MD (Committee Member) Subjects: Aging; Epidemiology; Ophthalmology

Doctor of Philosophy, The Ohio State University, 2018, EDU Teaching and Learning

This study addressed a lack of research within the field of orientation and mobility (O&M) regarding accessibility to public transportation, while exploring the effects of in-service training that addressed the role of bus drivers in serving consumers with visual impairments. The purpose of this mixed-methods research study was to explore the transportation needs of people with visual impairments, with a specific focus on the driver's role in assisting with these accessibility needs. Data was collected using (a) qualitative interviews with consumers, transit administrators, and bus drivers and (b) pre- and post-survey assessments to gauge effects of in-service training efforts. Analysis was completed using cross-references among qualitative interviews and pre- and post-survey data results, using a constant comparison model to analyze common themes and trends. Qualitative research outcomes indicated that transportation administrators are aware of ADA laws, that they have high expectations of their drivers, and take an active role in programs that support accessibility training. Consumers shared that public transportation has both positive and negative aspects, with recommendations for improvement that include (a) informing drivers that there are ways they can assist with accessibility, (b) interacting to make travel less stressful, and (c) providing in-service training that teaches drivers about the impact of vision loss on accessibility to public transportation. Drivers indicated that customer service is a top priority. Quantitative data collected through pre- and post-training surveys indicated, while driver attitudes as measured by the SRBS (Bell & Silverman, 2011) did not change significantly as a result of training, post-training survey data of driver knowledge and role in assisting passengers with vision loss differed from pre-survey data. There were benefits associated with the implementation of a driver in-service training that addressed the needs of (open full item for complete abstract)

Committee: Tiffany Wild (Advisor); Ann Allen (Committee Member); Melinda Rhoades (Committee Member) Subjects: Inservice Training; Rehabilitation; Special Education; Transportation

Doctor of Philosophy, The Ohio State University, 1983, Graduate School

Committee: Not Provided (Other) Subjects: Education

Doctor of Philosophy, University of Akron, 2016, Counseling Psychology

Much is yet unknown about Whites who take action for racial equity. This study investigated affective, ideological, and cognitive correlates of antiracist behavior using the recently developed antiracist behavior inventory. The study used cluster analysis to form groups of Whites according to psychosocial costs of racism, color-blind racial ideology, system justification beliefs, and social dominance orientation, and then determine differences in antiracist behavior between clusters. Cluster analysis revealed three types of Whites labeled The Status Quo, The Moderate, and The Beginning Antiracist. Cluster #1, The Status Quo, demonstrated the highest levels of CBRI, SJT, and SDO and the lowest levels of PCRW while Cluster #3, The Beginning Antiracist type endorsed the lowest levels of CBRI, SJT, and SDO, and the highest levels of PCRW. Cluster #2, The Moderate, were about average for the cluster on all variables. Significant differences were found between clusters on antiracist behaviors in a direction consistent with the literature. The Status Quo endorsed the lowest levels of ARBI while The Beginning Antiracist type endorsed the highest levels of antiracism in this sample. Findings indicated significant gender difference between groups where women were over-represented in all three groups due to sampling bias. However, Cluster 3, The Beginning Antiracist type, was comprised of about equal number of males and females. No age differences were noted. While many studies in the Whiteness literature have explored college samples, this study intentionally recruited community members.

Committee: Suzette Speight (Advisor); Carla Goar (Committee Member); Hewitt Amber (Committee Member); Li Huey-Li (Committee Member); Weigold Ingrid (Committee Member) Subjects: Counseling Psychology; Psychology; Social Research

PhD, University of Cincinnati, 2015, Arts and Sciences: Psychology

While race relations remain a divisive and controversial issue, very few studies examine the relationship between negative racial attitudes, American Values and Affirmative Action. This study examined the relationship of variables referred to here as “Perceiver Characteristics” (i.e., race, gender, and race saliency) and “Values Expectancy” (i.e., Modern Racism, Color Blindness, and American Values) to the endorsement of Affirmative Action Policy. This study recruited 207 undergraduate students to participate in an online survey using a battery of measures including the Attitude Toward Affirmative Action Scale (Kravitz & Platania, 1993), the Modern Racism Scale (McConahay, 1983), the Color-Blind Racial Attitudes Scale (Neville, Lily, Duran, Lee & Browne, 2000), The Multigroup Ethnic Identity Measure (Phinney,1992), and the American Values Scale (Citrin, Reingold & Green, 1990). The findings revealed that White males scored higher in Modern Racism than African American males and females, but not White females. White males also scored lower in Affirmative Action Endorsement than African American males, but not White and African American females. Color Blindness and Modern Racism were inversely related to the endorsement of Affirmative Action programs. The current study also found that individuals who identified as high in American Values tended to also be high in Modern Racism and Color Blindness. Lastly, study findings revealed that Modern Racism and Color Blindness mediated the relationship of both gender, and race to Affirmative Action policy endorsement. A key finding of this study was that a person's race, or gender, may influence their levels of Modern Racism, and/or Color Blindness, which may influence their Affirmative Action endorsement. Implications for future research are provided.

Committee: Ann Kathleen Hoard Burlew Ph.D. (Committee Chair); Farrah Jacquez Ph.D. (Committee Member); Laura Nabors Ph.D. (Committee Member) Subjects: Psychology

Master of Arts (M.A.), University of Dayton, 2014, Psychology, General

Although it is often assumed that law enforcement officers possess acute observational skills due to their expertise and training, perhaps resulting in a reduction in attentional errors (e.g., change blindness), no prior research has compared officers with a lay sample on this phenomenon. In the current investigation, students and law enforcement agents participated in a change blindness task and attempted to identify the target(s) from four photo lineups. Law enforcement officers (n = 61) and college students (n = 40) viewed a videotaped, mock traffic stop in which the identity of the driver was changed. Officers and students were equally susceptible to change blindness regarding the switch in the target's identity, but students were more likely than officers to detect changes in the target's clothing. Students also performed better on the lineup task, overall, than officers. Additionally, whereas students' confidence was positively correlated with identification accuracy under some circumstances, officers' confidence was either uncorrelated or negatively correlated with accuracy. Years of experience in police work did not account for any differences in the law enforcement sample. This comparison suggests that change blindness and mistaken identity are common attentional errors, perhaps even in situations involving specialized familiarity (i.e., a traffic stop is well within the professional domain of law enforcement officers). The findings of the current study also demonstrate the importance of continued research into law enforcement training and have practical implications for examinations of eyewitness identifications.

Committee: Melissa Berry Dr. (Committee Chair); Greg Elvers Dr. (Committee Member); Melissa Layman-Guadalupe Dr. (Committee Member) Subjects: Cognitive Psychology; Psychology

Master of Liberal Studies, University of Toledo, 2014, Liberal Studies

The eugenics movement targeted people who were blind and visually impaired as part of "the unfit" members of society who needed to be prevented from passing on their blindness to successive generations. In the late-nineteenth and early-twentieth centuries, eugenicists, blindness professionals, and even other blind people believed that the best way to eliminate blindness was through the restriction of marriages between blind people. Ophthalmologist Lucien Howe repeatedly attempted to secure legislation barring blind people from marrying. Blindness professionals, especially educators, stressed the importance of the separation of the sexes in residential schools for the blind as the way in which to prevent blind marriages and intermarriages, and thus to prevent future generations of blind people. Blind people's assessment of their own marriageability was complex and sometimes contradictory. While some shirked contemporary views, most others accepted and promoted the eugenic idea that hereditary blindness should not be passed to the next generation. Many historians have previously overlooked the unique and rich history of blind people in the United States. This research hopes to illuminate an important aspect of that history.

Committee: Kim Nielsen (Committee Chair); Liat Ben-Moshe (Committee Member); Diane Britton (Committee Member) Subjects: American History; Education History; Gender Studies; History; Personal Relationships; Special Education

MA, University of Cincinnati, 2011, Arts and Sciences: Psychology

Air battle management (ABM) operations places high demands on operator attention; operators are required to manage an airspace cluttered with aircraft, identify changes in amity of entities and respond appropriately to these aircraft. Awareness of the severe consequence of errors in detection and the risk of physical harm may contribute to operator stress and anxiety. Anxiety research shows a selective attention bias to threat-related information which, according to attentional control theory, impairs the inhibition and shifting stages of executive functioning related to attention. In the ABM context, task anxiety may increase change blindness by interfering with attentional processes. The current study aimed to observe these effects in dyads performing a simulated ABM task. Participants controlled fighter aircraft to destroy incoming enemy planes and protect their own assets. General aims of the study were to distinguish the impacts of trait and state anxiety on detection of target aircraft differing in threat, and to test the role of anxiety produced by a mood induction. Forty-six individuals were pre-screened for inclusion based on low and high trait anxiety such that teams of low, mixed and high trait anxiety might be compared. All teams performed the task in both neutral and anxious mood conditions. This experiment utilized a 3 × 3 × 2 × 2 mixed-model design. The between-groups factor was team composition (low anxious, mixed anxious, high anxious). Within-groups factors included trial mood state (Neutral-1/Anxious/Neutral-2), time, and target amity (neutral, low-threat, high-threat). The dependent measures collected in this experiment included measures of offensive and defensive performance in the air battle management task, measures of change detection, and three subjective state measures including the Dundee Stress State Questionnaire (DSSQ), State-Trait Personality Inventory (STPI) and the NASA Task Load Index (TLX). Team × Time mixed-model analyses of varia (open full item for complete abstract)

Committee: Gerald Matthews PhD (Committee Chair); Chung-Yiu Chiu PhD (Committee Member); Gregory Funke PhD (Committee Member); Benjamin Knott PhD (Committee Member); Michael Riley PhD (Committee Member) Subjects: Cognitive Psychology; Experimental Psychology; Military Studies; Personality Psychology; Psychology

Doctor of Philosophy, Case Western Reserve University, 2010, Physiology and Biophysics

Muller cells are the primary glia in the retina. These cells structurally and functionally maintain the retina and its vasculature. Therefore, it is possible that Muller cell dysfunctions, including cell death in a high glucose environment, contribute to the development of diabetic retinopathy. One of the changes that occur in retinal Muller cells in vitro and in vivo, under hyperglycemic conditions, is pro-death glyceraldehyde-3-phosphate dehydrogenase (GAPDH) nuclear accumulation. Interfering with GAPDH nuclear accumulation prevents cell death, demonstrating the therapeutic potential for this pathway. The goal of my dissertation research was to determine mechanisms that regulate GAPDH nuclear accumulation, and subsequent cell death under high glucose conditions in Muller cells. Transformed rat retinal Muller cells (rMC-l) and isolated human Muller cells (hMC) were used for our studies. Our results demonstrate that diabetic retinopathy-associated pro-inflammatory cytokines Interleukin-lβ (IL-1β) and Interleukin-6 (IL-6), differentially regulate GAPDH nuclear accumulation. Autocrine activation of the caspase-1/IL-1β signaling pathway strongly induces GAPDH nuclear accumulation and cell death while IL-6 is protective. In addition to examining cytokine regulation, our studies also demonstrate that the E3 ubiquitin ligase seven in absentia homolog (siah-l) facilitates GAPDH transport into the nucleus through formation of a complex with GAPDH. In contrast to GAPDH, siah-l has a nuclear localization signal (NLS) motif which potentially activates the shuttle function of this protein. Siah-l siRNA studies confirm the necessity for this protein during GAPDH nuclear accumulation. Exclusion of GAPDH from the nucleus using siah-siRNA prevents high glucose-induced activation of a well known cell death regulator p53. Interestingly, p53 activation is also regulated by the caspase-1/IL-1β signaling pathway. Additional events regulated by caspase-l include mitochondrial superoxide (open full item for complete abstract)

Committee: Susanne Mohr (Advisor); Cathleen Carlin (Committee Member); Joseph LaManna (Committee Member); Michael Simonson (Committee Member); Carole Liedtke (Committee Member); Andrea Romani (Committee Member); Corey Smith (Committee Chair) Subjects: Cellular Biology