Pathophysiology of Diabetic Retinopathy: Contribution and Limitations of Laboratory Research

Abstract

Preclinical models of diabetic retinopathy are indispensable in the drug discovery and development of new therapies. They are, however, imperfect facsimiles of diabetic retinopathy in humans. This chapter discusses the advantages, limitations, and physiological and pathological relevance of preclinical models of diabetic retinopathy. The judicious interpretation and extrapolation of data derived from these models to humans and a correspondingly greater emphasis placed on translational medical research in early-stage clinical trials are essential to more successfully inhibit the development and progression of diabetic retinopathy in the future.

Keywords: Diabetic retinopathy; Laboratory research; Preclinical models.

Fig 1.

Vascular histopathology of diabetic retinopathy progression is similar between species, differing mainly in the severity of the retinopathy that they develop (likely due at least in part to differences in life span). Diabetic patients can develop substantial microvascular pathology, including microaneurysms and degenerate capillaries, and in some cases, pre-retinal neovascularization. Similar lesions develop in large animal models of diabetic retinopathy, except that they have not been observed to develop pre-retinal neovascularization in the 5+ years of diabetes that they have been studied. Rodents develop predominantly only degenerate capillaries (large arrow) and pericyte ghosts (small arrow) and basement membrane thickening (not shown) in their limited lifetime. The duration of time needed for the various stages of the retinopathy in the different species are indicated in parentheses.