May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
Critical Role of MCP–1 in Photoreceptor Degeneration After Retinal Detachment in Mice
T. Nakazawa; A. Mastubara; K. Noda; T. Hisatomi; H. She; S. Miyahara; D. Skondra; A. Hafezi–Moghadam; J.W. Miller
Author Affiliations & Notes
  • T. Nakazawa
    Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Angiogenesis/Laser laboratory, Boston, MA
  • A. Mastubara
    Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Angiogenesis/Laser laboratory, Boston, MA
  • K. Noda
    Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Angiogenesis/Laser laboratory, Boston, MA
  • T. Hisatomi
    Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Angiogenesis/Laser laboratory, Boston, MA
  • H. She
    Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Angiogenesis/Laser laboratory, Boston, MA
  • S. Miyahara
    Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Angiogenesis/Laser laboratory, Boston, MA
  • D. Skondra
    Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Angiogenesis/Laser laboratory, Boston, MA
  • A. Hafezi–Moghadam
    Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Angiogenesis/Laser laboratory, Boston, MA
  • J.W. Miller
    Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Angiogenesis/Laser laboratory, Boston, MA
  • Footnotes
    Commercial Relationships  T. Nakazawa, None; A. Mastubara, None; K. Noda, None; T. Hisatomi, None; H. She, None; S. Miyahara, None; D. Skondra, None; A. Hafezi–Moghadam, None; J.W. Miller, None.
  • Footnotes
    Support  NIAID K08 A150775–02, P30 EY014104
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 4563. doi:
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      T. Nakazawa, A. Mastubara, K. Noda, T. Hisatomi, H. She, S. Miyahara, D. Skondra, A. Hafezi–Moghadam, J.W. Miller; Critical Role of MCP–1 in Photoreceptor Degeneration After Retinal Detachment in Mice . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4563.

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Abstract

Purpose: : To investigate whether monocyte chemoattractant protein–1 (MCP–1) plays a role in the photoreceptor degeneration that follows retinal detachment (RD).

Methods: : MCP–1 deficient (MCP–1–/–) and age–matched wild–type (WT) mice on the C57BL/6 genetic background were used in this study. RD was induced by subretinal injection of sodium hyaluronate. The expression of mRNA for MCP–1 was assessed by quantitative real time polymerase chain reaction (QPCR) at 72 h after RD. MCP–1 expression was determined by immunohistochemistry (IHC) and ELISA. Photoreceptor cell death was determined using a TdT–dUTP terminal nick–end labeling (TUNEL) assay. The number of TUNEL–positive cells and the thickness of the outer nuclear layer (ONL) 7 days after RD were compared in MCP–1–/– and WT mice. Acute blockade of MCP–1 was studied using a neutralizing Fab antibody (11K2, 0.5ug) injected subretinally in WT mice at the time of RD–induction and photoreceptor degeneration was quantified by TUNEL assay.

Results: : At day 3 after RD, significant increases were detected in mRNA (p=0.001, n=6) and protein levels (p=0.0018, n=6) for MCP–1 in the retinas of WT mice. IHC revealed that MCP–1 was increased in the Muller cells. Compared to WT, MCP–1–/– mice showed significantly (P<0.0001, n=10) less photoreceptor degeneration as determined by TUNEL assay. At day 7 after RD, the ONL thickness was decreased by 64.9% in WT mice, while MCP–1 –/– mice showed significantly less decrease of the ONL thickness (95.1%, P<0.0001, n=10). Subretinal administration of blocking MCP–1 Fab antibody significantly suppressed the number of TUNEL–positive cells in the ONL at 72 h after RD (P<0.0001, n=10).

Conclusions: : Lack of MCP–1 or its acute blockade with neutralizing Fab fragments protects against RD–induced photoreceptor degeneration in murine models. Our data suggest that MCP–1 plays a role in retinal degeneration associated with retinal detachment. Interference with MCP–1 may provide a new therapeutic approach for photoreceptor protection.

Keywords: photoreceptors • retinal detachment • inflammation 
© 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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