In vivo Models of Diabetic Retinopathy

Abstract

Diabetic animal models studied to date have developed some lesions characteristic of the early stages of diabetic retinopathy. This spectrum of lesions includes degenerate and nonperfused (acellular) capillaries, loss of capillary cells, thickening of basement membranes, and in longer-lived species, microaneurysms and intra-retinal microvascular abnormalities. To date, none of these diabetic animal models has been found to reliably develop preretinal neovascularization (an advanced stage of the retinopathy), likely due in part to less vaso-obliteration occurring during the short duration of diabetes that these models have been studied compared to diabetic patients. Although not diabetic, some animal models develop a diabetic-like preretinal neovascularization, and these models have been used to study ways to inhibit the neovascularization. Animal models are being used to provide valuable insight into the roles of specific biochemical pathways or physiological abnormalities in the development of diabetic retinopathy. Distinct advantages and disadvantages of each of these models are outlined in this review, thus providing information that should be valuable for planning experimental studies pertaining to the retinopathy.

Inflammation in diabetic retinopathy

“…An increase in the rate of appearance and disappearance of microaneurysms has been found to mark progression of the retinopathy, and to predict future reductions in visual function (Nunes et al, 2009). Microaneurysms have been detected also in diabetic dogs, cats, and primates, but have not been found to develop reproducibly in diabetic rodents (Kern, 2008; Zheng and Kern, 2010). …”

“…Capillary nonperfusion is not detectable clinically without infusion of a fluorescent dye (fluorescein) into the blood (Fig 1C), but degenerate capillaries are very apparent in isolated preparations of the retinal microvasculature (Fig 1D). Diabetes-induced degeneration of retinal capillaries has been observed to develop in all animal species tested to date (Kern, 2008; Zheng and Kern, 2010), but the extent of capillary nonperfusion and degeneration that has developed in diabetic animal models studied for only a few years or less is modest compared to that in some diabetic patients (likely explaining the failure of animal models to progress to preretinal neovascularization).…”

“…Administration of lovastatin and simvastatin to diabetic animals normalized the expression of the diabetes-induced increase in ICAM-1, VEGF and TNFα, and inhibited the decrease of tight junction (occludin) and adherens junction (VE-cadherin) proteins (Al-Shabrawey et al, 2008; Li et al, 2009a). The mechanism by which statins mediate this effect might involve mitochondrial-derived ROS (Zheng et al, 2010). Newer coumarin derivatives have also been shown to attenuate diabetes-induced alterations in retinal permeability, adhesion molecules, and cytokines (Bucolo et al, 2009).…”

“…It is well known that anti-VEGF therapies and steroids have potent effects on retinal edema and/or neovascularization, and intravitreal steroids downregulate VEGF and ICAM-1 expression and inhibit the activation of NF-κB (Wang et al, 2008). Similarly, blood pressure medications (such as captopril (Zhang et al, 2007) and perindopril (Zheng et al, 2009) and lipid lowering drugs (Zheng et al, 2010) inhibit capillary degeneration in diabetic retinopathy. These studies do not prove that beneficial effects of these therapies on retinopathy are mediated via anti-inflammatory actions, but it is worth further testing.…”

Management of diabetic complications: A chemical constituents based approach

“…Most studies on diabetic retinopathy till date have used type 1 diabetic animal models (Kern, 2009;Zheng and Kern, 2010 (Matsuura et al, 2005).…”