Age-dependent variations in the distribution of rat lens water-soluble crystallins. Size fractionation and molecular weight determination.

In order to obtain deeper insights into the mechanisms that are responsible for the age-related changes in the eye lens, the water-soluble proteins of 6-day-old to over 3-year-old rat lenses were analyzed by high-performance gel-permeation chromatography. Using this technique eleven crystallin fractions could be discerned: HM-, alpha-, three beta H-, two beta L-, beta S- and three gamma-crystallins. The concentrations of the higher molecular weight crystallins (HM-, alpha- and beta H-crystallin) seem to increase with age while those of the lower molecular weight (beta L- and gamma-crystallin) decrease. Taking into account the gradual increase of water-insoluble protein with aging, the relative amount of alpha-crystallin decreases from an age of 0.5 year after an initial increase. Additionally, an age-dependent increase in its molecular weight was found: from 7 . 10(5) to over one million. It appears that the gamma-crystallins are directly involved in the insolubilization process, while alpha- and beta L-crystallin first take part in aggregation processes leading to HM- and beta H-crystallin aggregates. These aggregation and insolubilization processes proceed gradually with increasing age. A steep decrease in gamma-crystallin concentration in the early phase of life, which also causes the relative increase in alpha-crystallin content in this period, may originate from a decrease in biosynthesis of certain gamma-crystallins.