Abstract
Purpose: :
Animal models which recapitulate most of the features of type II diabetic retinopathy (DR) are rare. We hypothesized that the Sand Rat Psammomys obesus, in which metabolic changes resembling type II diabetes have been described in captivity, might constitute such a model.
Methods: :
Young adult P. obesus were captured and maintained under captivity during 7 months, and fed either a natural vegetation-based diet (control group), or standard rat chow (test group). Compared to the control group, 40% of rat chow-raised individuals developed diabetes-like symptoms (increased body weight and blood glucose levels). Animals were killed, their eyes fixed in formaldehyde and retinas were processed for histology, immunohistochemistry and western blotting to examine changes in vasculature and identified retinal cell populations.
Results: :
Compared to controls, diabetic retinas showed statistically significant increases in retinal blood vessel thickness and branching, together with microaneurysms and pericyte loss. There were quantitative decreases in retinal cell layer thickness and densities, accompanied by profound alterations in glial cells (down-regulation of glutamine synthetase, glutamate-aspartate transporter and neural cell adhesion molecule, up-regulation of glial fibrillar acidic protein) and many neuronal populations (reduced expression of protein kinase Cα and , abnormal neurofilament). Cone photoreceptors were particularly affected, with reduced expression of cone opsins and transducin.
Conclusions: :
Simple dietary modulation of P. obesus induces a phenotype resembling type II diabetes. The retina undergoes a series of profound modifications similar to human DR, and makes this species a valuable novel model.
Keywords: diabetic retinopathy • immunohistochemistry • retinal degenerations: cell biology