Early Distal Axonopathy of the Visual Pathway in Experimental Diabetes

ROSENSTEIN RE; PASQUINI LA; DORFMAN D; ALDANA MARCOS HJ; FERNANDEZ DC

Fort Lauderdale

Congreso; Association for Research in Vision and Ophthalmology; 2012

Association for Research in Vision and Ophthalmology

Purpose Diabetic retinopathy is a leading cause of acquired blindness. Visual function disorders have been observed in diabetic patients with very early retinopathy or even before the onset of retinopathy. The aim of the present work was to analyze the visual pathway in an early stage of experimental diabetes. Methods Diabetes was induced in Wistar rats by an i.p. injection of streptozotocin. Anterograde transport was examined after an intravitreal injection of cholera toxin β-subunit. Apoptosis of ganglion cells was examined by TUNEL analysis, and the optic nerve levels of glial fibrillary acidic protein, platelet-derived growth factor receptor-α, and myelin basic protein were analyzed by immunohistochemistry. The optic nerve structure was examined by electron microscopy. Results A deficit in anterograde transport from the retina to the superior colliculus was observed 6 weeks after streptozotocin injection. At this time point, morphologic studies did not reveal retinal ganglion cell loss or substantial alterations in the superior colliculus. The optic nerve was morphometrically evaluated at intraorbital (unmyelinated and myelinated) and intracranial sections. In animals that had been diabetic for 6 weeks, a large increase in astrocyte reactivity occurred in the distal (but not the intraorbital) portion, which coincided with significant axon loss. Moreover, profound myelin alterations and altered morphologic features of oligodendrocyte lineage were observed at the distal (but not the proximal) optic nerve portion. Conclusions The present results suggest that axoglial alterations at the distal portion of the optic nerve could be the first structural change in the diabetic visual pathway.