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theses

Diabetic retinopathy (DR) is a common neovascular consequence of diabetes that leads to progressive vision loss in nearly a third of adult diabetics. The inner blood retinal barrier (iBRB) is the selective physiological barrier between neural cells and the vascular network that regulates metabolic and transport pathways. The iBRB is heavily regulated by Müller glia (MG), which envelop and connect neurons with endothelial cells (ECs) of the vasculature to provide structural and homeostatic support to regulate transport of oxygen, nutrients, and waste between the vasculature and retina. Hyperglycemia causes structural damage to capillary integrity and inflicts oxidative stress that stimulates angiogenesis and reactive gliosis of MG. New vasculature, however, is leaky, while prolonged MG reactive gliosis becomes inflammatory and promotes glial scarring, which may contribute to further damage and vision loss. Understanding MG cellular mechanisms used to form a physiological cell barrier with EC will highlight novel therapeutic targets to prevent chronic iBRB damage. Few projects have incorporated MG in studies of the iBRB, despite significant MG roles in disease progression and endogenous retinal repair. Significantly, the role of MG and estrogen is of interest because of widening health disparities in vision loss among older women in the United States.
This project examines the contribution of MG to the iBRB in diabetic retinopathy by investigating the bilateral relationship between MG and ECs in diabetic conditions with and without supplemental estradiol. Experiments were performed using conditioned media of primary MG and ECs to test the influence of one cell type to another. Data show that ECs significantly influence the morphology of MG in control and diabetic, to establish a unique relationship between these cells. Moreover, study of collective MG and EC responses were shown to affect the resistivity and permeability of an in vitro iBRB model using diabetic conditions with and without estradiol supplement. This project provides insight into the bilateral influence of MG and EC in diabetic retinopathy and highlights potential therapeutic effects of supplemental estradiol in adults.

http://dissertations.umi.com/gsnb.rutgers:12318

M.S.

Includes bibliographical references

doi:10.7282/t3-rgqn-aa05

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