Animal Models of Diabetic Retinopathy

Abstract

Purpose of Review Diabetic retinopathy (DR) is one of the most common complications associated with chronic hyperglycemia seen in patients with diabetes mellitus. While many facets of DR are still not fully understood, animal studies have contributed significantly to understanding the etiology and progression of human DR. This review provides a comprehensive discussion of the induced and genetic DR models in different species and the advantages and disadvantages of each model. Recent FindingsRodents are the most commonly used models, though dogs develop the most similar morphological retinal lesions as those seen in humans, and pigs and zebrafish have similar vasculature and retinal structures to humans. Nonhuman primates can also develop diabetes mellitus spontaneously or have focal lesions induced to simulate retinal neovascular disease observed in individuals with DR. Summary DR results in vascular changes and dysfunction of the neural, glial, and pancreatic β cells. Currently, no model completely recapitulates the full pathophysiology of neuronal and vascular changes that occur at each stage of diabetic retinopathy; however, each model recapitulates many of the disease phenotypes.

E2f1 mediates high glucose-induced neuronal death in cultured mouse retinal explants

“…For DR in vivo research, rodents are the most common models and play a critical role in understanding the disease. 6,7 However due to the short lifespan of the animals, rodent DR models cannot faithfully reproduce most important hallmark lesions typical of DR in spite of prolonged disease progression. 7,8 Cell culturebased approaches have proved invaluable for examining retinal cell types and how they respond to factors associated with diabetes, however since the retina is a complex, multi-cellular tissue, isolated cell cultures cannot reproduce the complex interplay of different retinal cell types in diabetes.…”

Analysis and Modeling of Polygonality in Retinal Tissue Based on Voronoi Diagram and Delaunay Tessellations

“…One of them is the temporal sequence of pathological changes in DR development [47,48]. Studies in rodents have highlighted that biomarkers of inflammation, such as leukostasis, overexpression of adhesion molecules in retinal vascular endothelial cells and leukocytes, vascular permeability alteration, and aggravated production of nitric oxide, prostaglandins, cytokines, and other inflammatory mediators appears in the retina during 1-6 months of diabetes crisis [49].…”

Pathological changes in the cellular structures of retina and choroidea in the early stages of alloxan-induced diabetes

“…A plethora of evidence obtained over the past 20 years based on different clinical studies and experimental data have shed more light on the development and pathogenesis of DR and how it develops[6,10,11,36,37]. However, the complexity of pathogenic pathways that lead to the development of DR is beyond the scope of this article and are reviewed elsewhere[5,6,10,11,36]. The typical histological picture of diabetes characterized by the destruction of stroma and cell elements was also described in a number of studies[37].…”

“…Because of this, DR is in the limelight of most clinical studies[1-4]. Hyperglycemia, hypertension, renal disease, and dyslipidemia, which are typical conditions in the manifestation of diabetes, have all been linked to the pathogenesis of DR[5,6]. According to the prevailing point of view, the leading causes of DR development include metabolic disturbances and vascular bed abnormalities, which accompany diabetes development[7-11].…”

“…One of them is the temporal sequence of pathological changes in DR development[19-22]. Studies in rodents have highlighted that biomarkers of inflammation, such as leukostasis, overexpression of adhesion molecules in retinal vascular endothelial cells and leukocytes, vascular permeability alteration, and aggrevated production of nitric oxide, prostaglandins, cytokines, and other inflammatory mediators appears in the retina during 1-6 mo of diabetes crisis[5]. Most developed therapies for DR, have primarily focused on the terminal stage of this disease, and as thus, failed to address the early potentially reversible stage of this disease.…”