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Impaired expression of thrombospondin-1 in eyes with age related macular degeneration
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  1. K Uno1,2,
  2. I A Bhutto1,
  3. D S McLeod1,
  4. C Merges1,
  5. G A Lutty1
  1. 1The Wilmer Ophthalmological Institute, Department of Ophthalmology, The Johns Hopkins Hospital, Baltimore, MD, USA
  2. 2Department of Ophthalmology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
  1. Correspondence to: Gerard Lutty PhD, 170 Woods Research Building, Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD 21287-9115, USA; galutty{at}jhmi.edu

Abstract

Aims: This study investigated the expression and localisation of thrombospondin-1 (TSP-1), a known anti-angiogenic extracellular matrix protein, in normal aged control human eyes and eyes with age related macular degeneration (AMD).

Methods: Immunohistochemical analysis with mouse anti-human TSP-1 antibody and mouse anti-human CD 34 antibody, as a blood vessel marker, was performed on frozen sections from macular and peripheral blocks of aged control donor eyes (n = 12; mean age 78.8 years), and eyes with AMD (n = 12; mean age 83.9 years). Pigment in retinal pigment epithelium (RPE) and choroidal melanocytes was bleached. Three independent observers scored the immunohistochemical reaction product.

Results: In the macular region, TSP-1 expression was observed intensely in Bruch’s membrane and weakly in RPE basement membrane, choriocapillaris, and the wall of large choroidal blood vessels in the aged control eyes. In eyes with AMD, TSP-1 immunoreactivity was significantly lower in all structures except RPE basement membrane (p<0.01). There was significantly lower TSP-1 in the far periphery than the equator and submacular regions in all eyes. TSP-1 immunoreactivity was low in choroidal neovascularisation (CNV), but it was high and diffuse in adjacent scar tissue.

Conclusion: These findings suggest that decreased TSP-1 in Bruch’s membrane and choroidal vessels during AMD may permit the formation of CNV.

  • AMD, age related macular degeneration
  • CNV, choroidal neovascularisation
  • ECM, extracellular matrix
  • HSPG, heparan sulfate proteoglycan
  • PEDF, pigment epithelium derived factor
  • RPE, retinal pigment epithelium
  • TSP-1, thrombospondin-1
  • age related macular degeneration
  • choroidal neovascularisation
  • thrombospondin-1
  • extracellular matrix
  • Bruch’s membrane
  • AMD, age related macular degeneration
  • CNV, choroidal neovascularisation
  • ECM, extracellular matrix
  • HSPG, heparan sulfate proteoglycan
  • PEDF, pigment epithelium derived factor
  • RPE, retinal pigment epithelium
  • TSP-1, thrombospondin-1
  • age related macular degeneration
  • choroidal neovascularisation
  • thrombospondin-1
  • extracellular matrix
  • Bruch’s membrane

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