Amelioration of light-induced retinal degeneration by a calcium overload blocker. Flunarizine.
Although free radical formation and lipid peroxidation have been implicated in photoreceptor degeneration following continuous light exposure, recent evidence led us to hypothesize that excessive stimulation of the photoreceptor cells in prolonged light exposure may cause intracellular calcium overload and consequent photoreceptor cell injury. To test this hypothesis, we studied the effects of flunarizine hydrochloride, a calcium overload blocker that inhibits the inositol 1,4,5-triphosphate-induced release of intracellular stores of calcium, in an established rat model of light-induced retinal degeneration. Light and electron microscopic examination of the flunarizine-treated retinas revealed remarkable preservation of the retinal pigment epithelium, rod inner and outer segments, nuclei, and synapses of the photoreceptor cells at all phases of the recovery period. This observation was further supported by morphometric evaluation of the outer nuclear layer thickness, which revealed a greater preservation of the photoreceptor nuclei in the drug-treated animals at 6 and 14 days after exposure. In addition, the rhodopsin levels in the flunarizine-treated retinas were also significantly higher than in the controls in all phases of recovery. The ability of flunarizine to ameliorate light-induced retinal degeneration in the rat supports our hypothesis that elevated intracellular calcium may indeed play a role in light-induced photoreceptor degeneration.
Edward
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Georgiana Dvorak Theobald Ophthalmic Pathology Laboratory, Department of Ophthalmology, University of Illinois, Chicago College of Medicine 60612.
Lam
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Shahinfar
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Li
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Tso
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D000818:Animals; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D005444:Flunarizine / Q000493:pharmacokinetics / Q000494:pharmacology*; D008027:Light / Q000009:adverse effects*; D010786:Photoreceptor Cells / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D011917:Rats, Inbred Lew; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D012162:Retinal Degeneration / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012243:Rhodopsin / Q000378:metabolism
D012243:Rhodopsin; D005444:Flunarizine; D002118:Calcium