Animal models of diabetic retinopathy

Abstract

The retina is the posterior neuro-integrated layer of the eye that conducts impulses induced by light to the optic nerve for human vision. Diseases of the retina often leads to diminished vision and in some cases blindness. Diabetes mellitus (DM) is a worldwide public health issue and globally, there is an estimated 463 million people that are affected by DM and its consequences. Diabetic retinopathy (DR) is a blinding complication of chronic uncontrolled DM and is the most common cause of blindness in the United States between the ages 24-75. It is estimated that the global prevalence of DR will increase to 191.0 million by 2030, of those 56.3 million possessing vision-threatening diabetic retinopathy (VTDR). For the most part, current treatment modalities control the complications of DR without addressing the underlying pathophysiology of the disease. Therefore, there is an unmet need for new therapeutics that not only repair the damaged retinal tissue, but also reverse the course of DR. The key element in developing these treatments is expanding our basic knowledge by studying DR pathogenesis in animal models of proliferative and non-proliferative DR (PDR and NPDR). There are numerous models available for the research of both PDR and NPDR with substantial overlap. Animal models available include those with genetic backgrounds prone to hyperglycemic states, immunologic etiologies, or environmentally induced disease. In this review we aimed to comprehensively summarize the available animal models for DR while also providing insight to each model's ocular therapeutic potential for drug discovery.

Keywords: Diabetes mellitus (DM); animal model; diabetic retinopathy (DR).

Figure 1

Features of DR. (A) Color fundus photo of the right eye of a patient with PDR, highlight pathologic changes which include ischemic damage to nerve fibers known as “cotton wool” spot (black arrow), dot-blot hemorrhages (white arrows), NVD (arrowhead) and NVE (double arrowhead). (B) The left eye of the same patient with PDR denotes advanced disease progression, highlighted are pathologic features including pre-retinal/sub-hyaloid bleeding [1] and VH [2]. (C,D) Corresponding FFA images. Pathological features shown here include MAs (dashed arrow) with corresponding features previously mentioned (A,B) and respectively denoted. Petaloid pattern of CME is encircled with dashed line. Area of capillary dropout is marked with asterix (*) and demarcated with dashed line. (E) OCT image of right eye shows cystoid macular edema CME that is more prominent in central macula (star). (F) OCT image of left eye. Hyper-reflective lesion (white arrow) representing pre-retinal/sub-hyoid hemorrhage. DR, diabetic retinopathy; PDR, proliferative diabetic retinopathy; NVD, neovascularization of the disc; NVE, neovascularization elsewhere; FFA, fundus fluorescein angiogram; MA, microaneurysm; VH, vitreous hemorrhage; CME, cystoid macular edema; OCT, optical coherence tomography.