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Thesis - Deoye Tonade.pdf (1.26 MB)

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ROLE OF PHOTORECEPTOR CELLS IN DIABETIC RETINOPATHY

Tonade, Deoye
http://rave.ohiolink.edu/etdc/view?acc_num=case1505440070603758

Abstract Details

2017, Doctor of Philosophy, Case Western Reserve University, Pharmacology.
In Chapter 1, we provide pertinent background information about diabetes, diabetic retinopathy (DR), and photoreceptor cells. Diabetes is a chronic metabolic disease giving rise to increased blood glucose over long periods of time (i.e. hyperglycemia), which can result in complications such as DR. DR is the leading cause of blindness in working age adults and is mainly characterized by retinal vascular damage. Most studies to date focus on the retinal vascular damage that occurs as a result of diabetes, but recent evidence suggests that photoreceptor cells play a major role in the progression of DR. Photoreceptor cells are the most abundant cells in the retina, and there are two types of photoreceptor cells, rods and cones. This thesis project focuses mainly on rod photoreceptors, because most of the animal work was carried out in rodents (which have rod-rich retina). In this thesis project, we sought to investigate the specific role of photoreceptor cells in diabetes-induced retinal inflammation and vascular damage. In Chapter 2, we described our studies aimed at determining whether or not photoreceptor cells themselves produced inflammatory proteins in the retina in diabetes. Using laser capture microdissection (LCM) to isolate the photoreceptor layer from diabetic mice, we showed increases in inflammatory proteins, ICAM1, iNOS, and COX2, compared to non-diabetic mice. Ex vivo studies demonstrated that leukocytes from diabetic mice lacking photoreceptor cells (opsin-/-) did not kill retinal endothelial cells compared to leukocytes from wild-type diabetic mice. Altogether, this evidence demonstrates that photoreceptor cells can produce inflammatory products, and these products can contribute to the death of retinal endothelial cells (i.e. via leukocyte activation) in diabetes. In Chapter 3, we describe our results looking at the contribution of photoreceptor cells to enhanced retinal vascular permeability in diabetes. We investigated if photoreceptor cells released products that can increase retinal endothelial cell and vascular permeability in diabetes. Our results demonstrated that the loss of photoreceptor cells inhibited the diabetes-induced increase in retinal vascular permeability. In addition, we provided evidence that photoreceptors in diabetes release a host of inflammatory products that may directly enhance permeability in retinal endothelial cells.
Johannes Von Lintig, Dr (Committee Chair)
George Dubyak, Dr (Committee Member)
Marcin Golczak, Dr (Committee Member)
Krzysztof Palczewski, Dr (Committee Member)
Timothy Kern, Dr (Advisor)
128 p.
Biomedical Research; Medicine
Diabetes, Retina, Photoreceptor Cells, Inflammation, Capillary Degeneration, Vascular Permeability

Recommended Citations

Citations

  • Tonade, D. (2017). ROLE OF PHOTORECEPTOR CELLS IN DIABETIC RETINOPATHY [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1505440070603758

    APA Style (7th edition)

  • Tonade, Deoye. ROLE OF PHOTORECEPTOR CELLS IN DIABETIC RETINOPATHY. 2017. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1505440070603758.

    MLA Style (8th edition)

  • Tonade, Deoye. "ROLE OF PHOTORECEPTOR CELLS IN DIABETIC RETINOPATHY." Doctoral dissertation, Case Western Reserve University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case1505440070603758

    Chicago Manual of Style (17th edition)

case1505440070603758
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© 2017, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.