May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
Critical Role of Apoptosis Inducing Factor (AIF) in Photoreceptor Apoptosis in Retinal Detachment
T. Hisatomi; T. Nakazawa; H. She; K. Noda; S. Miyahara; T. Ishibashi; G. Kroemer; E.S. Gragoudas; A. Hafezi–Moghadam; J.W. Miller
Author Affiliations & Notes
  • T. Hisatomi
    Angiogenesis, Mass Eye and Ear Infirmary, Harvard Medical School, Boston, MA
    Ophthalmology, Kyushu University, Fukuoka, Japan
  • T. Nakazawa
    Angiogenesis, Mass Eye and Ear Infirmary, Harvard Medical School, Boston, MA
  • H. She
    Angiogenesis, Mass Eye and Ear Infirmary, Harvard Medical School, Boston, MA
  • K. Noda
    Angiogenesis, Mass Eye and Ear Infirmary, Harvard Medical School, Boston, MA
  • S. Miyahara
    Angiogenesis, Mass Eye and Ear Infirmary, Harvard Medical School, Boston, MA
  • T. Ishibashi
    Ophthalmology, Kyushu University, Fukuoka, Japan
  • G. Kroemer
    Centre National de la Recherche Scientifique, Institut Gustave Roussy, Villejuif, France
  • E.S. Gragoudas
    Angiogenesis, Mass Eye and Ear Infirmary, Harvard Medical School, Boston, MA
  • A. Hafezi–Moghadam
    Angiogenesis, Mass Eye and Ear Infirmary, Harvard Medical School, Boston, MA
  • J.W. Miller
    Angiogenesis, Mass Eye and Ear Infirmary, Harvard Medical School, Boston, MA
  • Footnotes
    Commercial Relationships  T. Hisatomi, None; T. Nakazawa, None; H. She, None; K. Noda, None; S. Miyahara, None; T. Ishibashi, None; G. Kroemer, None; E.S. Gragoudas, None; A. Hafezi–Moghadam, None; J.W. Miller, None.
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 4573. doi:
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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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Abstract

Purpose: : 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.

Methods: : 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.

Results: : 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).

Conclusions: : 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.

Keywords: apoptosis/cell death • retinal detachment • photoreceptors 
© 2006, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2025 Association for Research in Vision and Ophthalmology.
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