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 (micrograms/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
phosphatidylethanolamine 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.(ABSTRACT TRUNCATED AT 250 WORDS)