Haem oxygenase-1 gene transfer protects retinal ganglion cells from ischaemia/reperfusion injury.
RGC (retinal ganglion cell) death following ischaemic insult is the major cause of a number of vision-threatening diseases, including glaucoma. The aim of the present study was to evaluate the role of HO-1 (haem oxygenase-1) in the retina against IR (ischaemia/reperfusion) injury. Adenovirus-mediated HO-1 gene transfer (Adv-HO-1) was carried out by injection into the vitreous body to induce HO-1 overexpression. At 3 weeks after transfection, levels of HO-1 expression, as measured by Western blot analysis, immunohistochemical staining and activity assay, were drastically up-regulated. Transient retinal ischaemia was induced by raising the intraocular pressure to 150 mmHg for 60 min. Untreated IR caused a significant decrease in RGC numbers at 3 and 7 days after reperfusion (76.1 and 67.2% of control eyes with sham IR respectively; P<0.001). Eyes pretreated with Adv-HO-1 had less RGC loss on day 3 and 7 following reperfusion compared with control eyes injected with Adv-GFP (adenovirus containing a gene for green fluorescent protein; 94.3 and 88.2% respectively; P=0.007 and 0.001). SnP (tin protoporphyrin), an HO-1 inhibitor, counteracted the effects of Adv-HO-1. In conclusion, these findings provide evidence that augmentation of HO-1 enzyme overexpression by intravitreal injection is able to protect RGCs against IR-induced damage.
Peng
Pai-Huei
PH
Department of Ophthalmology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan.
Ko
Mei-Lan
ML
Chen
Chau-Fong
CF
Juan
Shu-Hui
SH
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002470:Cell Survival; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D012160:Retina / Q000201:enzymology; D012164:Retinal Diseases / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000473:pathology*; D014162:Transfection; D015854:Up-Regulation
D051547:Heme Oxygenase-1