September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Potential of Human Donor Tissues for Discovery and Targeted Research on Diabetic Retinopathy
Author Affiliations & Notes
  • Patrice E Fort
    Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, United States
    Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, United States
  • Yangyang Qi
    Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, United States
  • Angela Myers
    Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, United States
  • Footnotes
    Commercial Relationships   Patrice Fort, None; Yangyang Qi, None; Angela Myers, None
  • Footnotes
    Support  NEI R01 EY020895; NIDDK Diabetic Complications Consortium (DiaComp, www.diacomp.org), grant DK076169; Eversight (previously Midwest Eye Banks)
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3214. doi:
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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)

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Abstract

Purpose : 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.

Methods : 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.

Results : 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.

Conclusions : 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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