Involvement of hyaluronan and its receptor CD44 with choroidal neovascularization

Hiroshi Mochimaru, Eri Takahashi, Nobuo Tsukamoto, Junichiro Miyazaki, Tomonori Yaguchi, Takashi Koto, Toshihide Kurihara, Kousuke Noda, Yoko Ozawa, Takatsugu Ishimoto, Yutaka Kawakami, Hidenobu Tanihara, Hideyuki Saya, Susumu Ishida, Kazuo Tsubota

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

PURPOSE. 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. (Invest Ophthalmol Vis Sci.

Original languageEnglish
Pages (from-to)4410-4415
Number of pages6
JournalInvestigative Ophthalmology and Visual Science
Volume50
Issue number9
DOIs
Publication statusPublished - 2009

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CD44 Antigens
Choroidal Neovascularization
Hyaluronic Acid
Light Coagulation
Lasers
Hymecromone
Macrophages
Real-Time Polymerase Chain Reaction
Messenger RNA
Choroid
Retinal Pigment Epithelium
Cell Adhesion Molecules
Neutralizing Antibodies
Oligonucleotide Array Sequence Analysis
Inbred C57BL Mouse
Extracellular Matrix

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

Involvement of hyaluronan and its receptor CD44 with choroidal neovascularization. / Mochimaru, Hiroshi; Takahashi, Eri; Tsukamoto, Nobuo; Miyazaki, Junichiro; Yaguchi, Tomonori; Koto, Takashi; Kurihara, Toshihide; Noda, Kousuke; Ozawa, Yoko; Ishimoto, Takatsugu; Kawakami, Yutaka; Tanihara, Hidenobu; Saya, Hideyuki; Ishida, Susumu; Tsubota, Kazuo.

In: Investigative Ophthalmology and Visual Science, Vol. 50, No. 9, 2009, p. 4410-4415.

Research output: Contribution to journalArticle

Mochimaru, H, Takahashi, E, Tsukamoto, N, Miyazaki, J, Yaguchi, T, Koto, T, Kurihara, T, Noda, K, Ozawa, Y, Ishimoto, T, Kawakami, Y, Tanihara, H, Saya, H, Ishida, S & Tsubota, K 2009, 'Involvement of hyaluronan and its receptor CD44 with choroidal neovascularization', Investigative Ophthalmology and Visual Science, vol. 50, no. 9, pp. 4410-4415. https://doi.org/10.1167/iovs.08-3044
Mochimaru, Hiroshi ; Takahashi, Eri ; Tsukamoto, Nobuo ; Miyazaki, Junichiro ; Yaguchi, Tomonori ; Koto, Takashi ; Kurihara, Toshihide ; Noda, Kousuke ; Ozawa, Yoko ; Ishimoto, Takatsugu ; Kawakami, Yutaka ; Tanihara, Hidenobu ; Saya, Hideyuki ; Ishida, Susumu ; Tsubota, Kazuo. / Involvement of hyaluronan and its receptor CD44 with choroidal neovascularization. In: Investigative Ophthalmology and Visual Science. 2009 ; Vol. 50, No. 9. pp. 4410-4415.
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abstract = "PURPOSE. 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. (Invest Ophthalmol Vis Sci.",
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AU - Mochimaru, Hiroshi

AU - Takahashi, Eri

AU - Tsukamoto, Nobuo

AU - Miyazaki, Junichiro

AU - Yaguchi, Tomonori

AU - Koto, Takashi

AU - Kurihara, Toshihide

AU - Noda, Kousuke

AU - Ozawa, Yoko

AU - Ishimoto, Takatsugu

AU - Kawakami, Yutaka

AU - Tanihara, Hidenobu

AU - Saya, Hideyuki

AU - Ishida, Susumu

AU - Tsubota, Kazuo

PY - 2009

Y1 - 2009

N2 - PURPOSE. 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. (Invest Ophthalmol Vis Sci.

AB - PURPOSE. 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. (Invest Ophthalmol Vis Sci.

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