Abstract
Purpose:
Retinal ischemia is a major contributor to vision loss in multiple diseases including acute angle-closure glaucoma, primary open angle glaucoma, diabetic retinopathy, and retinal vascular occlusions. The increase in oxidative stress is widely believed to play an important role in retinal ischemic injury. Sulforaphane, an isothiocyanate, and precursor of glucosinolate in cruciferous vegetables such as broccoli, has demonstrated neuroprotective effects in several experimental paradigms. It has been shown to protect neural cells in cell culture and animal models after stroke. In this study, we propose to determine the neuroprotective effects of sulforaphane on retinal ischemia in vivo, using a mouse model of ischemic-reperfusion injury in mice as quantified functionally. By quantifying relative changes in electrophysiology (ERG) (retinal function), the neuroprotective effects of sulforaphane are determined.
Methods:
Two groups of C56BL/6 wild type mice (6-8 weeks old) (n= 8 per group) were used for this study. The retinal ischemic-reperfusion injury was induced by elevation of intraocular pressure for 45 minutes. Following ischemic insult, vehicle (1% DMSO saline) or sulforaphane (25mg/kg/day) was administrated intraperitoneally once per day for 5 days. Retinal function was quantified by recording scotopic ERGs in dark-adapted mice prior to and one-week following ischemic insult.
Results:
Scotopic ERG a- and b-wave amplitudes prior to ischemic injury were 408 ± 82 mV and 856 ± 146 mV, respectively. Following ischemic-reperfusion injury, scotopic ERG a- and b-wave amplitudes of vehicle-treated mice were 152 ± 50 mV and 332 ± 87 mV, respectively. By comparison, ERG a- and b-wave responses from sulforaphane-treated mice were 306 ± 73 mV and 664 ± 123 mV, respectively.
Conclusions:
Intraocular ischemic-reperfusion insult elicits marked deficits in retinal function as quantified by scotopic ERG. Administration of sulforaphane protects against ischemic-reperfusion dependent deficits in retinal function. These preliminary findings suggest that sulforaphane may have therapeutic value in the early treatment of retinal ischemic diseases.
Keywords: 572 ischemia •
749 vascular occlusion/vascular occlusive disease