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M. P. Shyong, F.-L. Lee, W.-H. Hen, P.-C. Kuo, A.-C. Wu, H.-C. Cheng, S.-L. Chen, T.-H. Tung, Y.-P. Tsao; Attenuating Photoreceptor Apoptosis by Overexpression of Heme Oxygenase-1 in an Experimental Model of Retinal Detachment. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5221.
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To evaluate overexpression of heme oxygenase-1(HO-1) on photoreceptor apoptosis in an experimental model of retinal detachment (RD).
5 groups of Sprague-Dawley (SD) rats were studied: normal rats, rats receiving subretinal injection of recombinant adeno-associated virus expressing HO-1 (rAAV-HO-1), rats receiving subretinal rAAV-lacZ injection, rats receiving repeated intraperitoneal cobalt protoporphorin (CoPP, 5 mg/kg) injection, and rats receiving repeated PBS injection. RD was created in right eye after rAAV, CoPP and PBS administration. HO-1 expression was confirmed by immunofluorescence and Western blotting. Apoptotic cells and activation of caspase-3 was studied at 2 days of RD. The preservation of the thickness of photoreceptor outer nuclear layer (ONL) was evaluated at 28 days of RD.
Both rAAV-HO-1 delivery and CoPP administration lead to HO-1 overexpression. Subretinal rAAV-HO-1 delivery achieves localized high HO-1 gene expression in the ONL while systemic CoPP administration induced a diffuse, moderate expression of HO-1 throughout the retina. ONL thickness in eyes receiving rAAV-HO-1 injection was significantly higher than in rAAV-lacZ-treated or PBS-treated eyes at 28 days of RD, while CoPP treatment did not lead to significant ONL preservation (Kruskal-Wallis test, n = 6, P = 0.01). There were fewer TUNEL-positive cells (Kruskal-Wallis test, n = 5, P = 0.011) and less activated caspase-3 (Kruskal-Wallis test, n = 5, P = 0.011) in rAAV-HO-1 treated eyes than in control eyes, while CoPP had no such effect.
Both subretinal injection of rAAV-HO-1 and systemic CoPP administration led to the overexpression of HO-1 in the retina. rAAV-HO-1 injection resulted in fewer photoreceptor apoptosis than CoPP administration. This gene transfer approach may be a valuable adjuvant to current treatments for RD.
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