March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Protective Role of Soluble FasL in Photoreceptor Cell Loss
Author Affiliations & Notes
  • Dimosthenis Mantopoulos
    Retina,
    Massachusetts Eye & Ear Infirmary, Harvard, Boston, Massachusetts
  • Yusuke Murakami
    Department of Ophthalmology, Massachusettes Eye and Ear Infirmary, Boston, Massachusetts
  • George Trichonas
    Cleveland Clinic, Cleveland, Ohio
  • Meredith S. Gregory-Ksander
    Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts
  • Dean Cestari
    Neuro-ophthalmology,
    Massachusetts Eye & Ear Infirmary, Harvard, Boston, Massachusetts
  • Bruce R. Ksander
    Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts
  • Demetrios Vavvas
    Retina,
    Massachusetts Eye & Ear Infirmary, Harvard, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  Dimosthenis Mantopoulos, None; Yusuke Murakami, None; George Trichonas, None; Meredith S. Gregory-Ksander, None; Dean Cestari, None; Bruce R. Ksander, None; Demetrios Vavvas, None
  • Footnotes
    Support  The Research to Prevent Blindness Foundation, Lions Eye Research Fund, Onassis Foundation, NEI Grant EY014104 (MEEI core grant), Yeatts Family Fund
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 6361. doi:https://doi.org/
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      Dimosthenis Mantopoulos, Yusuke Murakami, George Trichonas, Meredith S. Gregory-Ksander, Dean Cestari, Bruce R. Ksander, Demetrios Vavvas; Protective Role of Soluble FasL in Photoreceptor Cell Loss. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6361. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Retinal detachment is characterized by photoreceptor loss and thinning of the retinal outer nuclear layer. FasL has been shown to mediate apoptotic cell death after retinal detachment. It exists in two forms, the membranous Fas Ligand (mFasL) that is thought to have proapoptotic activity and the soluble form of FasL (sFasL) that is thought to have pro-survival and anti-inflammatory properties. We wanted to investigate the role of soluble FasL in photoreceptor degeneration using the rodent model of retinal detachment.

Methods: : Wild-type and membrane-only FasL transgenic mice, also known as ΔCS, where the cleavage site in exon 2 of FasL was mutated were used. Experimental retinal detachment was created by subretinal injection of hyaluronic acid. Cell death was evaluated using TUNEL staining. Photoreceptor survival was assessed by measuring the relative thickness of the outer nuclear layer in histological sections. Levels of selected death and inflammatory cytokines were measured by ELISA.

Results: : Three days after retinal detachment, the normalized thickness of the outer nuclear layer decreased to 0.65 ± 0.09 in the no soluble FasL animals compared to 0.79 ± 0.09 (P = 0.002) in the wild type animals. TUNEL-positive cells in the detached retina of ΔCS animals were 2196 ± 215 comparing to, 1538 ± 107 in the WT (P = 0.013), after 3 days. The TNF-α levels were not significantly affected in the ΔCS animals.

Conclusions: : Absence of soluble FasL seems to potentiate photoreceptor cell loss in a rodent model of RD. Interfering with Fas signaling may have potential therapeutic effects in neurodegenerative retinal conditions

Keywords: retinal detachment • apoptosis/cell death • neuroprotection 
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