Regional distribution of lipids and phospholipase A2activity in normal and cataractous rat lens

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Abstract
The objectives of this study were to investigate the cause of the great difference in the concentration of phospholipids between the cortex and nucleus of the ocular lens and to further investigate the mechanism of cataract induction by the sterol synthesis-inhibitor U18666A. The nucleus of the young rat lens was found to contain less than one-third the concentration (µg/mg lens region, dry wt) of total phospholipid present in the cortex. The sterol to phospholipid molar ratio in the nucleus was more than double that in the cortex. Phosphatidylcholine plus phosphatidyl-ethanolamine were the principal phospholipids in both the lens cortex and nucleus. The activity of phospholipase A2 (PLA2), an enzyme important for turnover of cellular phospholipids, was measured in the total water-insoluble fraction from whole lenses and from isolated lens regions by the release of 1-14C-linoleic acid from the number two position of a synthetic phosphatidylcholine. The cortex was found to possess about 75% of the total PLA2 activity in the lens. Most of the remaining activity was in the nucleus. The low concentration of phospholipid in the lens nucleus could be due to breakdown of phosphoglycerides by PLA2 in the cortex as equatorial fiber cells shift toward the nucleus with aging. The cataract induced in rats by the sterol synthesis inhibitor U18666A was found to involve a major loss of total sterol from the lens cortex and almost total substitution of desmosterol for the cholesterol remaining in this region. By comparison, nuclear sterols were little affected by drug treatment and cataract development. Also, U18666A produced no major changes in the concentration or composition of phospholipids in the lens or in the activity of PLA2. The selective loss of sterol from the cortex could help to explain our recent finding that gap junctions, cholesterol rich membrane components, were completely lost from the plasma membrane of cortical fiber cells in cataractous rat lenses.