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Patrice E Fort, Yangyang Qi, Angela Myers; Potential of Human Donor Tissues for Discovery and Targeted Research on Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3214.
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© ARVO (1962-2015); The Authors (2016-present)
To better understand the mechanistic aspects of diabetic retinopathy by using tissues from human donors. We set to use human tissues to perform both targeted and discovery approaches to better analyze the impact of diabetes on retinal anatomy and function and compare to previous findings from animal models. While animal models have been and continue to be a great tool, they have their limitations, which emphasize the need for analysis on actual human tissues.
In addition to the information collected by the eye bank, donors disease state was characterized by post-mortem fundus photograph and optical coherence tomography (OCT). Regional anatomical changes were analyzed on one eye rapidly fixed using histological and immunohistochemistry methods. The contralateral eye was rapidly dissected in order to isolate the various ocular tissues as well as the different regions of the retina. The impact of diabetes on expression, phosphorylation and subcellular localization of various targets were analyzed by gene expression, biochemical, and proteomic-based methods.
This study clearly demonstrated the relationship between the progression of the disease and changes of expression of several members of the crystallin proteins family and other factors potentially associated with neurodegeneration and neuroinflammation. Those changes were shown to be not only tissue, but in some cases, even cell-specific in diabetic conditions. We for example showed that while expressed in other ocular tissues, several crystallins were primarily upregulated in the retina in a regional manner, and showed to be targeted by specific post-translational modification associated with alteration of function.
This work demonstrates how the use of tissues from human donor can complement work performed in animal models of diabetes and extend our understanding of the pathophysiology of diabetic retinopathy.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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