COX-2 inhibition improves retinal function in rats' ischemic eyes

Retinal ischemia is a relatively simple model for studies in pharmacological neuroprotective intervention. The role of cyclooxygenase (COX) enzymes in ischemic insult has been variously shown to either increase or decrease ischemic damage. The purpose of this study was to assess the role of COX-1 and COX-2 in rat retinal ischemic functional damage.

Ischemia was achieved by elevating intraocular pressure for 60 min. White flash electroretinogram (ERG) was recorded by contact lens electrodes containing an integral light emitting diode source. ERG was recorded on post-ischemia (PI) days-1 (baseline), 1, 3, and 7. The b-wave amplitude, b-wave implicit time, and oscillatory potentials (OPs) were analyzed. The expression of COX-2 and HSP70i was assessed by Western analysis on day 1 PI.

Ischemia caused attenuation of OPs, a decrease in the b-wave amplitude, and an increase in b-wave implicit time, accompanied by the increased expression of COX-2 and HSP70i proteins. Selective COX-2 inhibition markedly increased b-wave amplitude and enhanced retinal HSP70i induction, whereas COX-1 or nonselective and irreversible inhibition of both COX isoenzymes did not affect the retinal function or the expression of these proteins. High-dose aspirin prevented partial recovery from ischemic damage. Administration of a synthetic PGF2α analog, or a lipoxygenase inhibitor, had little effect on ischemic damage, but affected nonischemic ERG.

COX-2 appears to mediate some of the ischemic retinal functional damage, possibly by inhibiting the induction of HSP-70i. We propose that selective COX-2 inhibitors may be useful in pathological conditions involving ischemic retinal insult.