title: Involvement of hyaluronan and its receptor CD44 with choroidal neovascularization.
abstract: OBJECTIVE
  CD44 is a cell-surface adhesion molecule and receptor for hyaluronan (HA), one of the major extracellular matrix components. The purpose of the present study was to clarify a role of HA and CD44 in the development of choroidal neovascularization (CNV).
  
  
  METHODS
  Laser photocoagulation was used to induce CNV in C57BL/6 mice or CD44-deficient mice. The mRNA expression of CD44 and HA synthase (HAS)-2 in the retinal pigment epithelium (RPE)-choroid complex was evaluated by DNA microarray and real-time RT-PCR analyses 3 days after laser treatment. HA synthesis and CD44 expression were examined by immunohistochemistry 1 week after photocoagulation. Mice with laser-induced CNV were systemically administered the HA synthesis inhibitor 4-methylumbelliferone (MU) or an anti-CD44-neutralizing antibody. The response of CNV was analyzed by volumetric measurements 1 week after photocoagulation. Macrophage infiltration into CNV lesions was evaluated by real-time RT-PCR for F4/80 3 days after laser-induced injury.
  
  
  RESULTS
  The induction of CNV led to a significant increase in expression of CD44 and HAS2 mRNA. HA and CD44 were immunopositive in the CNV lesions. Compared with vehicle treatment, the systemic application of MU significantly attenuated CNV volume in a dose-dependent fashion, together with macrophage infiltration into the lesions. Consistently, antibody-based blockade of CD44 resulted in a significant reduction of CNV volume, compared with the isotype control. In contrast, genetic ablation of CD44 significantly augmented CNV formation together with HA accumulation and macrophage infiltration, compared with wild-type mice.
  
  
  CONCLUSIONS
  These results indicate a significant role of HA and its receptor CD44 in the development of CNV.
authors.affiliation: Department of Ophthalmology, Laboratory of Retinal Cell Biology, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mochimaru
authors.forename: Eri
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authors.lastname: Takahashi
authors.forename: Nobuo
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authors.lastname: Tsukamoto
authors.forename: Junichiro
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authors.lastname: Miyazaki
authors.forename: Tomonori
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authors.lastname: Yaguchi
authors.forename: Takashi
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authors.lastname: Koto
authors.forename: Toshihide
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authors.lastname: Kurihara
authors.forename: Kousuke
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authors.lastname: Noda
authors.forename: Yoko
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authors.lastname: Ozawa
authors.forename: Takatsugu
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authors.lastname: Ishimoto
authors.forename: Yutaka
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authors.lastname: Kawakami
authors.forename: Hidenobu
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authors.lastname: Tanihara
authors.forename: Hideyuki
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authors.lastname: Saya
authors.forename: Susumu
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authors.lastname: Ishida
authors.forename: Kazuo
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authors.lastname: Tsubota