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Argyrios Chronopoulos, Ekaterina Beglova, Sumon Roy, Kyle Trudeau, Keith G. Mansfield, Lynn M. Wachtman, Sayon Roy; Development of a Non-human Primate Model of Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5961.
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© ARVO (1962-2015); The Authors (2016-present)
The paucity of animal models exhibiting full spectrum characteristics of diabetic retinopathy (DR) has been an impediment in the development of therapies for DR. Most animal models lack certain key changes in the retina, in part due to the anatomical absence of the macular region. In this study we have determined if hyperhexosemic marmosets (Callithrix jacchus) would develop characteristic vascular lesions including macular edema, a significant clinical complication of DR.
Four marmosets were maintained on a 30% galactose (gal)-rich diet for 2 years. Non-diabetic marmosets were maintained on regular diet as controls. A spontaneously diabetic marmoset with ~8 months of hyperglycemia was also included in the study for histological assessment. Fasting blood glucose was monitored routinely, HbA1c level measured at ~4 month intervals, and retinal scans using optical coherence tomography (OCT) were recorded at 12, 20 and 23 month time points. Retinal vascular permeability was measured using FITC-albumin injection followed by analysis of retinal whole mounts. Moreover, retinas from all eyes were subjected to trypsin digest, stained with PAS and hematoxylin and assessed for vascular lesions.
A significant increase in HbA1c and fasting blood glucose levels confirmed hyperhexosemia in the galactose-fed marmosets and the diabetic marmoset compared to those of control marmosets. OCT analysis revealed modest thickening of the macular area (205µm±11) and a more prominent thickening of the surrounding macular tissue (273µm±12) in the gal-fed marmosets compared to those of the control primates (156µm±19 and 248µm±11 respectively). Vascular permeability assay showed increased retinal capillary leakage in the gal-fed primates compared to those of controls. Few microaneurysms were detected in two of the four gal-fed marmosets. The number of acellular capillaries and pericyte loss was significantly increased (60%, 37%, respectively). In the diabetic and the gal-fed marmosets compared to those of control, increased number of acellular capillaries, pericyte loss and retinal vascular basement membrane thickness was observed.
The findings suggest that hyperhexosemia can induce many features of diabetic retinopathy including microaneurysms, mild retinal edema and retinal vascular leakage in the marmoset. This could potentially be a suitable model for studies of diabetic maculopathy and retinopathy.
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