Roles of cyclooxygenase-1 and -2 during retinal degeneration in a mouse model of retinal ischemia

Abstract

Background: Cyclooxygenase (COX) is a kind of key enzyme in the conversion of arachidonic acid to prostaglandins participating in certain physiological and pathological processes like inflammation. Studies of Alzheimer’s disease indicate that the two COX isoforms, COX-1 and COX-2 are involved mainly in neuroinflammation and neuroprotection respectively. Material and Methods: An acute retinal ischemia model was introduced in COX-1 and COX-2 mutated mice by elevating the intraocular pressure to 90 mmHg constantly for 60 minutes. Retinas got collected at post-surgery day of 3, 7, and 14 for morphology and molecular study and data analysis. C57BL mice were used as control group. Results: Our recent study showed that in an acute retinal ischemia model, both COX-1 and COX-2 mutant mice showed significant survival rate of retinal ganglion cells compared to wild-type mice. At 14-day after surgery of retinal ischemia, the survival retinal ganglion cells (RGCs) remains at 43% and 45% to total population in COX-1 and COX-2 mutated mice, while the wild-type group has only 24% RGCs survived. During the degeneration of RGCs, microglia got suppressed in COX-2 deficient retinas compared to COX-1 retinas, suggesting COX-2 modulates the inflammation pathways while COX-1 plays a more important role in neuroprotection in RGCs degeneration. Conclusions: These results suggests that COX-1 and COX-2 deficiency could preserve RGCs from degeneration via neuroprotection and anti-inflammation respectively, which differs from the mechanism in the brain. Acknowledgements: This study was supported by grants from HKU Small Project Funding and HKU Seed Funding for incubating group-based collaborative research projects.