Increased expression of oxyproteins in the optic nerve head of an in vivo model of optic nerve ischemia

BACKGROUND: To investigate the effects of microvascular compromise on the expression of oxidative proteins in the optic nerve head. METHODS: Endothelin-1 (0.1 μg/day) was delivered to the perineural region of the anterior optic nerve by osmotically driven minipumps for two, four, and eight weeks in ten rabbits, respectively. As a control, a balanced salt solution was delivered for two and eight weeks in five rabbits, respectively. Expression of oxyproteins in the cornea, vitreous, retina, and optic nerve head for each time period was determined using the OxyBlot protein oxidation detection kit. Retina was stained with H&E and TUNEL for histological examination. RESULTS: There was a significant increase in the expression of oxyproteins in the optic nerve head after two weeks of endothelin-1 administration (p < 0.001, Mann Whitney U test). In contrast, there was no expression of oxyproteins in the cornea, retina, or vitreous. The number of cells in the retinal ganglion cell layer, inner nuclear layer, and outer nuclear layer decreased remarkably with time in the endothelin-1-treated group. Furthermore, the inner and outer nuclear layers, as well as the inner and outer plexiform layers, became thinner over time. CONCLUSIONS: Administration of endothelin-1 to the microvasculature of the optic nerve leads to increased expression of oxyproteins in the optic nerve head and loss of retinal ganglion cells.