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Ling Zhi Heng, Ali A Hussain, John Marshall; The effect of varying levels of active MMP on hydraulic conductivity across aged Bruch’s membrane.. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1320.
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Both sequestration and a reduction in the free levels for activation of MMP-2 have been demonstrated in Bruch’s membrane from AMD donor eyes. In-vitro laser activation of RPE explants has shown energy-dependent increase in the release of activated-MMP2. The aim of the present study was to determine if graded increases in the level of activated MMP-2 have corresponding effects (if any) on the hydraulic conductivity of Bruch’s membrane from aged eyes.
Macular samples of human Bruch’s-choroid were obtained from 19 donors in the age range 50-80 years. These samples were mounted in open-type Ussing chambers and basal hydraulic conductivity determined. Samples were then incubated with varying levels of activated MMP-2 (1.5-30nM) followed by re-assessment of hydraulic conductivity.
Compared to basal levels, hydraulic conductivity increased by 0.211+/-0.830 to 4.623+/-2.635 x10-7m-1sec -1Pa -1 in samples incubated with 1.5 and 30nM activated MMP-2 respectively. The increase in hydraulic conductivity was linearly related to the concentration of activated MMP-2 (R=0.670, p<0.05).
Active MMP increases hydraulic conductivity across aged Bruch’s in a concentration dependent manner. Hence, modulations of laser parameters which increase levels of active MMP 2 release can improve the function of Bruch’s membrane and must be considered when designing future clinical protocols.
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