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K. Uno, I.A. Bhutto, C.A. Merges, D.S. McLeod, G.A. Lutty; Expression and Localization of Thrombospondin–1 in Aged Human Eyes and Eyes With Age–Related Macular Degeneration . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5284.
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Purpose: It has been hypothesized that age–related macular degeneration (AMD) is caused by the disruption of the balance between pro–angiogenic and anti–angiogenic factors in the Bruch’s membrane/retinal pigment epithelium (RPE)/choriocapillaris complex. This study investigated the expression and localization of thrombospondin–1 (TSP–1), a known anti–angiogenic extracellular matrix protein, in normal aged human eyes and eyes with AMD. Methods: Immunohistochemical analysis with mouse anti–TSP–1 antibody and mouse anti–CD 34 antibody, as a blood vessel marker, was performed on frozen sections (inferior macula) of aged human eyes (n=12, age range, 70–86 years; mean age, 78.8 years), and eyes with AMD (n=12, age range, 61–105 years; mean age, 83.9 years). Pigment in RPE and choroidal melanocytes was bleached (Bhutto et al, IOVS. 2004;45:1544). Three independent observers scored the immunohistochemical reaction product. In addition, hematoxylin and eosin staining, and periodic acid Schiff staining were performed to examine the morphology. Results: In the aged control eyes, TSP–1 expression was observed intensely in Bruch’s membrane and weakly in RPE basal lamina, choriocapillaris, and adventitia of choroidal blood vessels. On the contrary, in the eyes with AMD, TSP–1 expression was significantly lower in Bruch’s membrane, choriocapillaris, and adventitia of blood vessels (P < 0.01). There was no significant difference in the RPE basal lamina. In the areas of choroidal neovascularization (CNV), the expression of TSP–1 was quite low, but it was high and diffuse in adjacent scar tissue. Conclusions: These findings suggest that impaired expression of TSP–1 in choroid and Bruch’s membrane during AMD may be permissive for formation of CNV. TSP–1 may also modulate the regression of CNV in disciform scars.
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