Photoreceptor protection against light damage by AAV-mediated overexpression of heme oxygenase-1

Ming Hui Sun, Jong Hwei Su Pang, Show Li Chen, Ping Chang Kuo, Kuan Jen Chen, Ling Yuh Kao, Ju Yun Wu, Ken-Kuo Lin, Yeou-Ping Tsao*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

43 Scopus citations


PURPOSE. To investigate whether overexpression of the cytoprotective gene heme oxygenase-1 (HO-1) in photoreceptors by gene delivery attenuates cellular injury caused by intense light damage and to document the possible mechanisms of protection. METHODS. Recombinant adeno-associated virus type 5 (rAAV5) expressing the mouse HO-1 gene (mHO-1) was delivered to cyclic-light reared Sprague-Dawley (SD) rats by subretinal injection. Three weeks after transfer of HO-1 gene, animals were subjected to 2-hour intense light exposure then were returned to darkness. Expression of HO-1, p53, p38, and cellular FLICE inhibitory protein (c-FLIP) at different times after intense light damage was evaluated by Western blot analysis. HO-1 transgene expression, along with expression of c-fos and bcl-2, was analyzed by immunohistochemistry. In addition, the protective effects of HO-1 were evaluated by determining the morphology of the retina. Finally, apoptosis in photoreceptors was measured using TdT-dUTP terminal nick-end labeling (TUNEL) 24 hours after photic injury. RESULTS. Exogenous administration of HO-1 by gene transfer led to HO-1 transgene expression in photoreceptors. Protection of retina by HO-1 overexpression is evident from the partially preserved retina structure and attenuated apoptosis in photoreceptors after photic injury. Concurrently, overexpression of HO-1 was associated with a decrease in the expression of c-fos and p53, an increase in the activation of p38 and bcl-2, and preserved the expression of c-FLIP. CONCLUSIONS. Overexpression of HO-1 in photoreceptors protected themselves from subsequent cellular damage caused by intense light exposure. The anti-apoptotic mechanisms of HO-1 may be related to the induction of p38, bcl-2, and c-FLIP and to the suppression of c-fos and p53.

Original languageEnglish
Pages (from-to)5699-5707
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Issue number12
StatePublished - 12 2007


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