Viral delivery of heme oxygenase-1 attenuates photoreceptor apoptosis in an experimental model of retinal detachment.
This study was designed to evaluate the efficacy of subretinal injection of recombinant adeno-associated virus vector expressing heme oxygenase-1 (rAAV-HO-1) in attenuating photoreceptor apoptosis induced by experimental retinal detachment (RD) in Sprague-Dawley rats. Our results disclosed that subretinal rAAV-HO-1 delivery achieved localized high HO-1 gene expression in retinal outer nuclear layer (ONL) compared with rAAV-lacZ-injected eyes and eyes with RD left untreated both at 2 (p=0.003) and 28 (p=0.007) days of RD. The ONL thickness (p=0.018) and mean photoreceptor nuclei count (p=0.009) in eyes receiving rAAV-HO-1 injection was significantly higher than in rAAV-lacZ-injected or eyes with RD left untreated at 28 days of RD. There were fewer apoptotic photoreceptor nuclei at 2 (p=0.008) and 5 (p=0.018) days of RD and less activated caspase-3 expression (p=0.008) at 2 days of RD in rAAV-HO-1 treated eyes than in control eyes. These data supported that gene transfer approach might attenuate photoreceptor apoptosis caused by RD with a resultant better ONL preservation.
Shyong
Mong-Ping
MP
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
Lee
Fenq-Lih
FL
Hen
Wen-Hua
WH
Kuo
Ping-Chang
PC
Wu
Ai-Ching
AC
Cheng
Huey-Chung
HC
Chen
Show-Li
SL
Tung
Tao-Hsin
TH
Tsao
Yeou-Ping
YP
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D004789:Enzyme Activation; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000201:enzymology; D012163:Retinal Detachment / Q000201:enzymology / Q000473:pathology / Q000628:therapy*
D051547:Heme Oxygenase-1; D053148:Caspase 3