Animal models of diabetic retinopathy: doors to investigate pathogenesis and potential therapeutics

Abstract

Effective and validated animal models are valuable to investigate the pathogenesis and potential therapeutics for human diseases. There is much concern for diabetic retinopathy (DR) in that it affects substantial number of working population all around the world, resulting in visual deterioration and social deprivation. In this review, we discuss animal models of DR based on different species of animals from zebrafish to monkeys and prerequisites for animal models. Despite criticisms on imprudent use of laboratory animals, we hope that animal models of DR will be appropriately utilized to deepen our understanding on the pathogenesis of DR and to support our struggle to find novel therapeutics against catastrophic visual loss from DR.

Small GTPase ARF6 controls VEGFR2 trafficking and signaling in diabetic retinopathy

“…To provide a more complete clinical representation of diabetic retinopathy in vivo, we tested the protective effects of the ARF6 small-molecule inhibitor NAV-2729 in oxygen-induced retinopathy (OIR), which has been used as a mouse model for proliferative diabetic retinopathy (29). We found that, as in mice treated with SU4312, NAV-2729 treatment significantly inhibited the extent of retinal neovascularization in OIR (Supplemental Figure 5E).…”

Animal Models of Diabetic Retinopathy

“…As this model has only been maintained for 28 days to date, several attributes including similar retinal topography, ease of vascular structures visualization with fluorescent expression [33,83], short life span, and large breeding size reduce experimental time and make zebrafish a strong model to study DR [27].…”

“…Several high-sugar diet models have been developed including mice, rats, rabbits, dogs, and zebrafish [33,43,44,60,[78][79][80][81][82][83] that were persistently exposed to galactose developing retinopathy similar to that observed in human diabetes. Maintenance of galactose exposure results in continued disease progression.…”

“…Cats generally do not develop cataracts [32]. Pigs and zebrafish, in contrast, are preferred for the similarity of their eye structure to humans, easily visualized vascular structures, short life spans, and large breeding sizes (zebrafish) [27,33,34]. Though no single animal model to date represents the complete range of vascular and neural complications of human DR in both early and late stages, the models described in this review have been instrumental in determining the mechanisms behind DR in the hopes of developing novel therapies.…”

Neuropeptides, Trophic Factors, and Other Substances Providing Morphofunctional and Metabolic Protection in Experimental Models of Diabetic Retinopathy

“…During the preclinical phase of diabetes drug research, it is indispensable to perform experiments on a reliable animal model to mimic diabetes-related complications. Recently, several reviews have been published summarizing the existing methods for the investigation of diabetic eye disorders in rodents (Islam, 2013;Jo et al, 2013;Kong et al, 2013;Robinson et al, 2012). Nowadays, a number of diabetes models are well known and widely used, but only a few of them offer a thorough examination of the diabetic manifestations in their complexity.…”