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M. G. Friedrich, R. J. W. Truscott; Age-Dependent Association of Proteins With Membranes in the Human Lens. Is This the Basis for the Barrier?. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2100.
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In the middle-aged human lens, a barrier to the diffusion of small metabolites forms, and it has been proposed that this underlies the later development of nuclear cataract. In this study, the aim was to determine the biochemical basis for the barrier.
The nuclear regions of human lenses (aged 20-72) were dissected and fractionated by sucrose density gradient centrifugation. Changes in protein and membrane density were examined by SDS PAGE, HPLC and mass spectrometry.
Marked changes in protein density were observed in human lenses as a function of age. The most pronounced changes occur between the ages of 40 to 50. This was accompanied by a > 90% loss of ‘native’ membrane lipids which, after the age of 50, sedimented with protein at higher densities. This finding can be explained by the large-scale accumulation of crystallins onto cell membranes in the centre of older lens. Such a process may lead to obstruction of membrane pores.
Massive binding of crystallins to fibre cell membranes takes place at the same time as barrier formation in the lens is observed. This suggests that the association of formerly soluble crystallins with membranes may be responsible for the formation of the barrier via the occlusion of connexon and aquaporin 0 pores.
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