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C. Tsilfidis, A. N. Baker, J. Brousseau, I. Szymanska, W. W. Hauswirth, D. N. Zacks; The X-Linked Inhibitor of Apoptosis (XIAP) Preserves Photoreceptors in Experimentally Induced Retinal Detachment. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1536.
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Various studies have shown that photoreceptor apoptosis plays a role in the pathophysiology of retinal detachment. Since XIAP is a member of a family of genes that inhibits apoptosis by blocking the function of caspases, the current study examined the efficacy of XIAP gene therapy in the neuroprotection of photoreceptors following retinal detachment.
Serotype 5 adeno-associated virus (AAV) encoding either XIAP or GFP, driven by the chicken beta-actin (CBA) promoter, was injected subretinally into one eye of adult male Brown Norway rats. Two weeks after the AAV injection, retinas were detached by injecting sodium hyaluronate into the subretinal space in the region of the AAV injection. Retinas were sampled at 3 days and at 2 months after the detachment. TUNEL analysis, histology and immunohistochemistry were used to assess structural integrity of the retina.
XIAP conferred significant and long-term structural protection to photoreceptors in retinal detachment. TUNEL analysis, which identifies dying cells, revealed that XIAP-treated eyes had significantly fewer apoptotic nuclei in comparison to GFP-treated controls. Outer nuclear layer thickness was also significantly preserved at sites of XIAP over-expression. No preservation of retinal morphology was seen in the GFP-injected controls.
The current study shows that XIAP is able to preserve the structure of photoreceptors in experimentally induced retinal detachment. This suggests that decreasing the susceptibility of the retinal cells to apoptotic death may allow more time for successful re-attachment of the retina and improve the visual outcome in patients with retinal detachment.
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