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World J Diabetes. Mar 15, 2015; 6(2): 312-320
Published online Mar 15, 2015. doi: 10.4239/wjd.v6.i2.312
Current knowledge on diabetic retinopathy from human donor tissues
Jessica H Eisma, Jennifer E Dulle, Patrice E Fort
Jessica H Eisma, Jennifer E Dulle, Patrice E Fort, Departments of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, Ann Arbor, MI 48105, United States
Author contributions: Eisma JH wrote the first draft of the paper; Dulle JE and Fort PE edited, corrected and formatted the manuscript.
Conflict-of-interest: Patrice E Fort has received research funding from the National Eye Institute (NIH-NEI); Patrice E Fort is an employee the University of Michigan; none of the authors have any conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Patrice E Fort, PhD, Departments of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, 1000 Wall Street, Ann Arbor, MI 48105, United States. patricef@umich.edu
Telephone: +1-734-2328225 Fax: +1-734-2328030
Received: September 17, 2014
Peer-review started: September 20, 2014
First decision: December 17, 2014
Revised: December 23, 2014
Accepted: December 29, 2014
Article in press: December 31, 2014
Published online: March 15, 2015
Abstract

According to the American Diabetes Association, diabetes was the seventh leading cause of death, and diabetic retinopathy the leading cause of blindness in working age adults in the United States in 2010. Diabetes is characterized by hyperglycemia associated with either hypoinsulinemia or insulin resistance, and over time, this chronic metabolic condition may lead to various complications including kidney failure, heart attacks, and retinal degeneration. In order to better understand the molecular basis of this disease and its complications, animal models have been the primary approach used to investigate the effects of diabetes on various tissues or cell types of the body, including the retina. However, inherent to these animal models are critical limitations that make the insight gained from these models challenging to apply to the human pathology. These difficulties in translating the knowledge obtained from animal studies have led a growing number of research groups to explore the diabetes complications, especially diabetic retinopathy, on tissues from human donors. This review summarizes the data collected from diabetic patients at various stages of diabetic retinopathy and classifies the data based upon their relevance to the main aspects of diabetic retinopathy: retinal vasculature dysfunction, inflammation, and neurodegeneration. This review discusses the importance of those studies to discriminate and establish the relevance of the findings obtained from animal models but also the limitations of such approaches.

Keywords: Retina, Diabetic retinopathy, Human donor, Physiopathology, Vascular disease, Inflammation, Neurodegeneration

Core tip: This review summarizes the current state of the knowledge on the physiopathology of diabetic retinopathy directly obtained from the analysis of tissues from human patients strongly complementing what has been gathered from animal models. The review discusses the vascular, inflammatory and neurodegenerative aspects of the disease, their inter-relation and the advantages and limits of such studies compared to the ones using animal models. Altogether, these analyses clearly demonstrate the complexity of the disease mechanisms but also the somewhat still limited knowledge and the need for additional complementary studies.