Vitreal oxygenation in retinal ischemia reperfusion.

Several ocular and systemic diseases (e.g., central retinal artery occlusion, carotid artery disease, diabetic retinopathy, and possibly glaucoma) are accompanied by retinal ischemia, which is a common cause of visual impairment and blindness.1 Retinal ischemia results in neuronal cell degeneration and activation of glial cells. Neuronal cell degeneration is caused by oxygen and substrate deprivation during ischemia and by reperfusion injury.1,2 Apoptosis (programmed cell death without necrosis) has been cited as a potential pathway of retinal ganglion cell death in both human glaucoma and experimental primate glaucoma associated with elevated IOP.2–4 In the eye, growth factor deprivation of retinal ganglion cells results from the blockade of retrograde transport at the lamina cribrosa, preventing growth factors from reaching their site of action in the cell body.5,6 When the IOP is elevated, the choroidal blood flow decreases, leading to a reduction in approximately 0.5 mm Hg choroidal partial oxygen pressure/1 mm Hg perfusion pressure.7–10 This reduction leads to a reduction in photoreceptor oxygen availability and consumption.10 Similarly, anything that decreases choroidal blood flow would be expected to have a negative impact on retinal oxygenation and on photoreceptor function. Experimental glaucoma has been shown to affect photoreceptors,11 possibly because of a reduction in the photoreceptor oxygen supply. There is also direct evidence of retinal damage by reduced choroidal blood flow in birds.12 Several studies have shown that retinal oxygenation can be partially or completely restored during arterial occlusion by making the animal hyperoxic.13–16 Studies using models of total ischemia have corroborated the importance of oxygen as the limiting factor during occlusion. Anderson and Saltzman17 have shown that if human subjects breathed oxygen before IOP elevation, their vision was sustained longer than if they breathed room air. Blair et al.18 have shown that perfusing the vitreous with an oxygenated solution after total occlusion can maintain the structural and electrophysiological integrity of the retina. Despite these positive experimental data, the clinical experience with hyperoxia has been mixed, with only few studies recommending hyperoxia as a treatment for vascular occlusion.19 In the present study, we present a novel system for vitreal oxygenation using electrolysis of the water content of the vitreous gel. Specifically, our aim was to evaluate the potential role of anterior vitreal oxygenation, by oxygen-generating electrodes, for reversing ischemic insult in a rabbit model with ischemia reperfusion.