Long term effects of diaminophenoxypentane in the rat retina: protection against light damage.
The retinotoxic drug diaminophenoxypentane (DAPP) was administered to rats to determine its long term effects on rhodopsin levels, retinal morphology and the retina's susceptibility to damage from visible light. In rats given 2 intraperitoneal injections of DAPP at doses of 65 mg/kg body wt, there was a dramatic and sustained loss of rhodopsin. One wk later visual pigment levels were 41% lower than in comparable dark maintained rats injected with saline. Rhodopsin levels in the DAPP treated rats remained lower than in control animals for the 13 wk period of the study. Morphologically, the ROS of rats 1-2 wks after DAPP treatment exhibited some disorganization and shortening; the RPE was unremarkable. Seven wks after DAPP treatment an occasional focal area of damage was seen in the RPE. Similarly, focal areas of degeneration were seen in the outer nuclear layer between the rows of photoreceptor cells. As determined by photoreceptor cell nuclear counts, the retinotoxic effect of DAPP persisted long after drug administration. In the treated rats the loss of visual cell nuclei was 11% at 7 wks; it was 22% 13 wks after DAPP treatment. Immediately after exposure to intense visible light, damage was seen in both the photoreceptor cells and RPE of DAPP treated rats. However, the effects of exposure in the treated rats were less dramatic than in retinas from rats without DAPP treatment. Following a 2 wk dark recovery period, the DAPP treated rats had a normal appearing retinal morphology and an intact RPE layer. The retinas of rats without DAPP treatment showed extensive visual cell and RPE loss.(ABSTRACT TRUNCATED AT 250 WORDS)
Wang
H M
HM
Department of Biochemistry and Molecular Biology, Wright State University, Dayton, OH 45435.
Hull
B E
BE
Organisciak
D T
DT
D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D003623:Dark Adaptation; D007274:Injections, Intraperitoneal; D008027:Light / Q000009:adverse effects*; D008137:Longitudinal Studies; D008297:Male; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D012162:Retinal Degeneration / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D012243:Rhodopsin / Q000378:metabolism; D012374:Rod Cell Outer Segment / Q000187:drug effects / Q000473:pathology
D000814:Aniline Compounds; C000900:1,5-bis(p-aminophenoxy)pentane; D012243:Rhodopsin