Andreas Ebneter, Glyn Chidlow, John Wood, Robert Casson
The Ocular Hypertension Treatment Study (OHTS) reported that diabetes protected against the conversion of ocular hypertension (OHT) to glauco-matous optic neuropathy (GON). Hyperglycemia is neuroprotective in rodent models of acute retinal isch-emia and chronic retinal hypoperfusion. The aim of the current work was to investigate the effect of short-term hyperglycemia on optic nerve damage in a rat model of experimental glaucoma.
Experimental GON was induced in a group of normoglycemic (n = 26) and a group of hypergly-cemic (n = 26) Sprague-Dawley rats by layering the trabecular meshwork using a standard protocol. After two weeks of elevated intraocular pressure, rats were killed by transcardial perfusion.Axonal loss was graded semi-quantitatively on trans-verse sections of the optic nerve. Longitudinal sections were immunohistochemically stained for glial markers. The histological/immunohistochemical outcomes were compared using unpaired, non-parametric statistics.
The degree of axonal loss following 2 weeks of experimental glaucoma was significantly lower in the hyperglycemic group of rats compared to the nor-moglycemic group. Axonal loss was reduced by 54%.
Underlying hyperglycemia appeared to be protective in this rat model of experimental GON after 2 weeks of OHT. Possible explanations for this effect are the attenuation of malperfusion induced energy failure by increasing the substrate for glycolysis or a shift in metabolism resulting in reduction of ROS-induced apoptosis.