Histologic Characterization of Retina Neuroglia Modifications in Diabetic Zucker Diabetic Fatty Rats

Abstract

Purpose: The purpose of this study was to characterize retinal degenerative morphologic modifications in Zucker Diabetic Fatty (ZDF) rats, a genetic model of type 2 diabetes, by histologic and immunohistochemical evaluation.

Methods: Male lean (?/+; n = 10) and ZDF (fa/fa; n = 20) rats were used. At 24 weeks of age, body weights and blood glucose levels were determined. Eyes were removed and processed for paraffin wax embedding. Sections through the optic disc were stained for hematoxylin and eosin or immunostained for TUNEL, advanced glycation end products (AGEs), glial fibrillary acidic protein (GFAP), glutamate/aspartate transporter (GLAST), isolectin B4, recoverin, retinal pigment epithelium-specific 65-kDa protein, rhodopsin, vimentin, and zonula occludens protein 1. Retinal morphometry, cell counts, glial activation degree and immunoreactivity of AGEs and GLAST were also determined.

Results: ZDF rats were observed to be diabetic from week 9 and by week 24. These animals showed retinal morphologic degenerative changes, increased neuroretinal thickness, and decreased number of nuclei. Glial cells activation with massive GFAP upregulation was present. Cellular morphologic modifications were also observed. GLAST immunofluorescence was decreased, whereas AGEs were increased in comparison with lean rats.

Conclusions: Spontaneous development of diabetes in ZDF rats results in neuroglia morphologic degenerative changes at 24 weeks of age. This animal model may be useful to understand the pathogenesis of diabetic retinopathy and to screen neuroprotective drugs in diabetes.