Protection of Photoreceptors by Antioxidants OT–551and OT–674 in a Rat Model of Light–Induced Retinal Degeneration

Abstract

Purpose: : OT–551 and OT–674 are antioxidants; OT–551 has been shown to prevent hydrogen peroxide–induced cataracts in an in vitro model. In the present study, we tested the efficacy of OT–551 and OT–674 in the protection of photoreceptor cells in an acute light damage model of retinal degeneration.

Methods: : Albino rats born and raised in 5–10 lux cyclic light were exposed to 2,700 lux fluorescent light for 6 hours. One eye was covered and served as a non–exposed control. OT–551 and OT–674 (provided by Othera Pharmaceuticals) were administered by intraperitoneal injection 30 min prior to light stress (OT–551, 50 mg/kg; OT–674, 100 mg/kg). Retinal neuroprotection by these drugs was evaluated morphologically by quantitative histology and functionally by electroretinography (ERG). In addition, we tested a putative protective mechanism by comparing the levels of the transcription factor c–fos in nuclear protein fractions from light–damaged, drug–treated, and control retinas.

Results: : Our results revealed that a single intraperitoneal injection of each drug significantly protected against acute light–induced photoreceptor degeneration in comparison to a sterile water control. Although the protective effect by OT–551 was more apparent than OT–674, there was no statistical difference between protection afforded by these two drugs. The administration of OT–551 did not affect c–fos levels in nuclear fractions compared to controls. In addition, there were no significant differences in ERG b–wave amplitudes or in outer nuclear layer thickness between drug– or water–treated rats that were not exposed to light, indicating that these drugs are not toxic to retinal cells.

Conclusions: : Systemic administration of OT–551 and OT–674 provides functional and morphological protection of retinal photoreceptor cells against acute light damage in rats. The mechanism(s) underlying this protection remains to be determined.

Keywords: retinal degenerations: cell biology • antioxidants • photoreceptors