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S Swamy-Mruthinti, JE Hansen, J Russell, S Mruthinti; Structure-Function Relationship of AQP0 in Human Cataract Lenses . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4644.
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Purpose: Our earlier studies with diabetic rat lenses showed that AQP0 undergoes protein modifications and C-terminus truncation with a concomitant decrease in water permeability function. This study is aimed to show possible structural and functional changes of AQP0 in human cataract lenses. Methods: Human lenses with posterior subcapsular cataract, nuclear cataract and mature cataract were obtained from India, and age-matched control lenses were obtained from a local eye bank. Large unilamellar membrane vesicles were prepared from lens cortical fibers and the water permeability was measured from the rate of volume change of these vesicles in hypertonic solution. AQP0 was isolated from human control and cataract samples in 2% octyl-glucoside to study secondary and tertiary protein structural changes by Circular dichroism (CD) spectropolarimetery. Advanced glycation end products (AGEs) were measured immunochemically. Results: There was a significant increase in the levels of AGEs (particularly carboxymethyl lysine, the major glyxodation product) in the lens membranes of cataract samples compared to respective controls (p<0.001). Mature and nuclear cataracts have higher levels of AGEs compared to subcapsular cataracts (p<0.05). There was an increase in the degradation of AQP0 as well as aggregation to high molecular weight species (40-60kd or more) in cataract lenses compared to controls. Preliminary analysis of secondary and tertiary structures by CD showed significant differences in the human cataract samples compared to controls. Water permeability function was decreased by about 2-3 fold compared to controls (p<0.05) Conclusions: Taken together, this data suggests that decreased water permeability function of AQP0 in human cataract lenses is due to structural alterations and protein modifications. Since water flow is the internal micro-circulatory system for the avascular lens, inefficient water flow would result in the accumulation of metabolic wastes resulting in cataract formation.
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