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Motohiro Kamei, Joe G. Hollyfield; TIMP-3 in Bruch’s Membrane: Changes during Aging and in Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 1999;40(10):2367-2375.
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purpose. To assess the distribution, content, and function of tissue inhibitor
of metalloproteinases (TIMP)-3 during aging in normal eyes for
comparison with the levels observed in eyes with age-related macular
methods. Donor tissues analyzed included 36 normal eyes (14–96 years old) and
15 AMD eyes (74–98 years old). A tissue strip including the fovea was
used for immunohistochemistry. Western blot analysis was performed on
extracts of the retinal pigment epithelium (RPE)–choroid complex from
the posterior part of each eye. Immunoreactivity of TIMP-3 bands in
each western blot was densitometrically quantitated. The inhibitory
function of TIMP-3 was evaluated with reverse zymography.
results. TIMP-3 was present uniformly across Bruch’s membrane in the normal
samples. In samples from donors more than 50 years of age,
immunostaining was intense. TIMP-3 content ranged from 92 to 1061
ng/cm2 and increased with age (r = 0.66). In
AMD eyes, TIMP-3 distribution in Bruch’s membrane was abundant in
areas of continuous soft drusen but absent in areas below RPE atrophy.
TIMP-3 levels in AMD eyes were significantly higher than in age-matched
normal eyes (577 versus 877 ng/cm2; P =
0.009). Inhibitory activity correlated well with TIMP-3 content
(r = 0.82) and was also significantly higher in AMD eyes
than in age-matched normal eyes (P < 0.001).
conclusions. During normal aging, TIMP-3 content in Bruch’s membrane of the macula
shows a significant increase. TIMP-3 content in AMD eyes was elevated
relative to that of age-matched normal eyes. Higher levels of TIMP-3
may contribute to the thickening of Bruch’s membrane observed in
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