April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Osteopontin Drives Fibrosis in a Mouse Model of Neovascular Age Related Macular Degeneration
Author Affiliations & Notes
  • Sally S. Ong
    Ophthalmology,
    Duke University Eye Center, Durham, North Carolina
  • Goldis Malek
    Ophthalmology and Pathology,
    Duke University Eye Center, Durham, North Carolina
  • Diego G. Espinosa-Heidmann
    Ophthalmology,
    Duke University Eye Center, Durham, North Carolina
  • Karen Wu
    Ophthalmology,
    Duke University Eye Center, Durham, North Carolina
  • Peter Saloupis
    Ophthalmology,
    Duke University Eye Center, Durham, North Carolina
  • Maria G. Spiga
    Ophthalmology,
    Duke University Eye Center, Durham, North Carolina
  • Scott W. Cousins
    Ophthalmology,
    Duke University Eye Center, Durham, North Carolina
  • Footnotes
    Commercial Relationships  Sally S. Ong, None; Goldis Malek, None; Diego G. Espinosa-Heidmann, None; Karen Wu, None; Peter Saloupis, None; Maria G. Spiga, None; Scott W. Cousins, None
  • Footnotes
    Support  American Health Assistance Foundation and Research to Prevent Blindness
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 942. doi:
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      Sally S. Ong, Goldis Malek, Diego G. Espinosa-Heidmann, Karen Wu, Peter Saloupis, Maria G. Spiga, Scott W. Cousins; Osteopontin Drives Fibrosis in a Mouse Model of Neovascular Age Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2011;52(14):942.

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

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Abstract

Purpose: : In neovascular age-related macular degeneration (AMD), macrophages are recruited to choriocapillaries in response to various chemotactic signals for scavenging, repair or inflammation. In severe choroidal neovascularization (CNV), recruited macrophages express profibrogenic growth factors that produce the extensive remodeling, arteriolization and fibrosis observed in anti-VEGF therapy resistant patients. These profibrogenic growth factors regulate osteopontin (OPN) expression in vascular smooth muscle cells. We hypothesize that OPN, an important mediator of macrophage recruitment and retention, may regulate the development of severe CNV. Previously, we demonstrated that macrophage infiltration, number of vascular smooth muscle cells and CNV lesion size were reduced in OPN knockout mice when compared to age-matched controls. To further evaluate the role of OPN in the development of the severe CNV subtype, we investigated the level of fibrosis in the CNV lesions of OPN knockout mice.

Methods: : Experimental laser was induced in old (14-16 months) OPN knockout (B6.Cg-Spp1tm1Blh/J) and age-matched C57BL/6 wild type mice. Three weeks post laser induction, the left eyes were enucleated, cryopreserved and sectioned for immunohistochemistry. Cryosections were probed with markers for collagen type IV and deposition of collagen type IV was analyzed.

Results: : The level of collagen type IV deposition in the CNV lesions of OPN knockout mice was reduced by 56% when compared to age-matched controls. This result was independent of CNV lesion size.

Conclusions: : The amount of fibrosis in the experimental CNV lesions of OPN knockout mice was greatly decreased when compared to age-matched controls; these results suggest a direct role for osteopontin in regulating fibrotic CNV. This study offers support to the theory that crosstalk between OPN and profibrogenic growth factors secreted by activated macrophages drives the severe CNV subtype.

Keywords: age-related macular degeneration • neovascularization • inflammation 
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