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Ali A. Hussain, Yunhee Lee, JinJun Zhang, John Marshall; Characterisation Of The Gelatinase Component Of The Matrix Metalloproteinase (MMP) System At The Human Optic Nerve Head Region. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3859.
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Matrix metalloproteinases (MMPs) play a pivotal role in maintaining the fluidity of the ECM of the lamina cribrosa. Some of the MMPs involved in the turnover of the ECM have been identified but little is known of the distribution of active and latent forms, their age related transformations or the degree of proteolytic activity present. Our purpose was to identify the presence of individual components of the gelatinase MMP system and to quantify the level of activity of these enzymes in the optic nerve head and surrounding rim region of the human fundus.
Samples of optic disc, rim region and Bruch’s membrane-choroid from macular and peripheral regions were isolated from 12 donor eyes ranging in age between 60-72 years. MMPs were extracted with non-reducing sodium dodecyl sulphate (SDS) sample buffer and separated by gelatin zymography. Individual gelatinase species were identified by their respective molecular weights and levels quantified by standard densitometric techniques. Ratios of active/latent MMPs were calculated as representative indicators of the degree of proteolytic activity at each of the locations examined.
All of the gelatinase species normally found in Bruch’s membrane were also present at the optic nerve head. The greater presence of the high molecular weight species (HMW1 & HMW2) at the ONH was indicative of the age-related accumulation of the polymerisation products of MMPs 2&9. The relative distribution of MMPs 2&9 found in Bruch’s was reversed at the ONH and the surrounding rim area. Active levels of MMPs 2&9 at the ONH and rim region were considerable raised in comparison to their latent forms indicative of the much greater turnover of the matrix in these regions (p<0.005).
The components of the gelatinase pathway mediating matrix turnover in Bruch’s membrane were also present at the ONH. The presence of high levels of active MMPs 2&9 at the ONH and rim area is indicative of a high rate of matrix remodelling in these regions. Enhanced matrix turnover at the ONH may represent an important mechanism for maintaining the plasticity of the lamina cribrosa but the reason for high MMP activity in the rim region and its relevance to the biomechanics of the ONH requires further investigation.
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