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T. Hisatomi, T. Nakazawa, H. She, K. Noda, S. Miyahara, T. Ishibashi, G. Kroemer, E.S. Gragoudas, A. Hafezi–Moghadam, J.W. Miller; Critical Role of Apoptosis Inducing Factor (AIF) in Photoreceptor Apoptosis in Retinal Detachment . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4573.
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© ARVO (1962-2015); The Authors (2016-present)
Apoptotic photoreceptor death is one of the major causes of visual loss after retinal detachment (RD). Previously, we reported the translocation of the apoptosis inducing factor (AIF) from the mitochondrial intermembrane space into the nucleus during RD. To further elucidate the role of AIF in RD–induced retinal degeneration, we quantified photoreceptor apoptosis in AIF deficient mice (Hq/Y) after experimentally induced RD.
Eyes of wild type (wt) and hemizygous AIF deficient mice were enucleated at 1, 3, and 6 months of age to determine retinal developmental differences. RD was induced by subretinal injection of sodium hyaluronate in age–matched wild type and AIF deficient (Hq/Y) mice. The animal’s eyes were enucleated on days 1, 3, and 7 after RD, and were analyzed using immunohistochemistry, and transmission electron microscopy (TEM). To quantify photoreceptor apoptosis, double staining of terminal nick end labeling (TUNEL) and AIF immunohistochemistry was observed by fluorescent microscopy.
Hemizygous AIF deficient mice showed a continued retinal cell apoptosis during the first 6 months of their life. The ratio of apoptotic photoreceptors to total photoreceptors was 0.24% in AIF deficient mice and 0% in wt mice of 3 or 6 months (n=6). RD–induced photoreceptor apoptosis was evaluated in 3 month old mice. Following RD, photoreceptor apoptosis was significantly lower in AIF deficient mice (2.4%) when compared to wt (5.1%, n=5 in each group, p=0.016).
Our data suggest that AIF plays an important role in the RD–induced photoreceptor apoptosis. AIF deficiency is associated with chronic apoptosis of photoreceptors. However, mice lacking AIF show a surprising protection against RD–induced neurodegeneration. AIF may thus offer a new therapeutic target for neuroprotection after RD.
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