TIMP-3 Distribution and Content in Bruch’s Membrane and the Choroid Is Different in Caucasian and African American Donor Eyes

Abstract

Abstract: : Purpose: Age-related macular degeneration (AMD) occurs more frequently in lightly pigmented individuals of Northern European extraction than in more heavily pigmented individuals of African extraction. To determine whether specific molecular differences are present in the connective tissue below the RPE of the macula, we defined the distribution and content of TIMP-3 in Bruch’s membrane between age-matched Caucasian and African American donor tissues. Methods: Donor eyes used were between 50 and 85 years of age, 11 from African American donors and 12 from Caucasian donors. Bruch’s membrane and choroid from the macula from each donor eye were prepared for immunocytochemistry and Western blotting and differences in immunoreactivity were quantitated. Results: TIMP-3 immunoreactivity was present in broader areas in Bruch’s membrane and connective tissue surrounding the choriocapillaris in the Caucasian samples than was observed in the African American samples. Additionally, quantitation of Western blots indicated that Caucasian tissues show a progressive increase in TIMP-3 content with age, whereas African American tissues show near steady state levels over the same age ranges. Conclusions: TIMP-3 has been proposed to be one of the candidate proteins involved in age-related macular degeneration. Our study suggests that the susceptibility of Caucasians to AMD may be related to the progressive accumulation of proteins in Bruch’s membrane and surrounding tissues that could alter the exchange of metabolites between the RPE and choriocapillaris.

Keywords: Bruch's membrane • age-related macular degeneration • retinal pigment epithelium