Amelioration of retinal photic injury by a combination of flunarizine and dimethylthiourea.
Free radical scavengers and a calcium overload blocker have been demonstrated separately to ameliorate light-induced retinal degeneration, suggesting that both free radical formation and increased intracellular calcium levels are involved in the pathologic changes of this disease process. To understand the relationship between these two mechanisms, we studied the ameliorative effects of combined treatment with flunarizine and dimethylthiourea as well as individual treatment with either drug in a rat model of light-induced retinal degeneration. At 6 hr and 6 and 14 days after light exposure, morphologic and morphometric studies of the retinas from the rats receiving the combined treatment demonstrated better-preserved retinal pigment epithelial cells, photoreceptor elements, and nuclei than did retinas from rats receiving treatment with either flunarizine or dimethylthiourea alone. Rhodopsin level measurements at 6 and 14 days further substantiated the results of the protective effects on the photoreceptor outer segments. Because we used a saturating dose for dimethylthiourea, the enhanced ameliorative effect of the combination treatment suggested that free radical formation and elevated intracellular calcium levels were two separate mechanisms in light-induced retinal degeneration.
Li
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Georgiana Dvorak Theobald Ophthalmic Pathology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois, Chicago 60612.
Edward
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D000818:Animals; D004359:Drug Therapy, Combination; D005444:Flunarizine / Q000627:therapeutic use*; D008027:Light / Q000009:adverse effects; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D012160:Retina / Q000473:pathology; D012162:Retinal Degeneration / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D013890:Thiourea / Q000031:analogs & derivatives* / Q000627:therapeutic use
C038983:1,3-dimethylthiourea; D013890:Thiourea; D005444:Flunarizine