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Cibin T Raghavan, Mareen Smuda, Marcus Glomb, Annapurna Singh, Pankaj Gupta, Ram H Nagaraj; AGE-modifications in human lens capsule: Implications for posterior capsule opacification. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5722.
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Proteins in basement membrane are long-lived and accumulate chemical modifications during aging. The reaction of carbonyl compounds that results in the formation of advanced glycation end products (AGEs) is a major chemical modification in basement membrane proteins. Human lens capsule is a basement membrane secreted by lens epithelial cells. In this study we have investigated the effect of age and cataract on AGE modification in human lens capsules. The overall objective is to determine the effects of capsule AGEs on secondary cataract formation.
Lens capsules from normal lenses were isolated from donor lenses. Anterior capsule from cataractous lenses were collected from the capsulorhexis procedure during cataract surgery. AGE estimations were done using fluorescence HPLC and LC/MS. Human lens epithelial cells isolated from a 48-year donor lens was cultured on glycated or non-glycated Type IV collagen or basement membrane extract (BME). Glycation of the culture plates coated Type IV collagen or BME was carried out by incubating with one of the following two glycating mixtures: 1) low glycating mixture (LG): 2 mM ascorbate, 5 mM glucose and 100 μM methylglyoxal and 2) high glycating mixture (HG): 2 mM ascorbate, 25 mM glucose and 250 μM methylglyoxal for one week. Cell adhesion, proliferation and migration of lens epithelial cells on AGE-modified or control matrices were assessed by standard procedures.
Fluorescent AGEs pentosidine and argpyrimidine were present in significantly higher amounts in the capsules of cataractous lenses when compared to those of age-matched normal lenses. The levels of these two AGEs were higher in the capsules of diabetic cataracts relative to those in senile cataracts. A number of other AGEs were identified by the LC/MS method, which are being quantified. Lens epithelial cell adhesion was significantly reduced in cells cultured on both LG and HG glycated collagen or BME relative to cells cultured on unmodified cell matrix. Similarly, cell proliferation and migration were significantly reduced in cells cultured on glycated matrices relative to those on non-glycated matrices.
Higher AGE content in the capsules of cataractous lenses could promote lens epithelial cell transformation into mesenchymal phenotype by negatively affecting cell proliferation and migration.
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