Age-related changes in the protein concentration gradient and the crystallin polypeptides of the lens

With the use of a freeze-sectioning technique, the existence of a centripetal protein gradient in the rabbit lens is demonstrated. The steepness of this gradient (the difference in the protein concentration between periphery and the center) varies with age: it increases from a value of 40% in 6- to 8-month-old lenses to 60% by the age of 4 to 5 years and then begins to decline at an average rate of about 5% per year, reaching a value below 40% in 9-year-old lenses. The decline in protein concentration gradient is reciprocated by a gain in the water content. Electrophoretic evidence shows that the decline in the protein gradient is preceded and accompanied by postsynthetic modification of lens crystallin polypeptides. Modifications result in the formation of crosslinked material that stays on the top of sodium dodecyl sulfate gels and of degraded polypeptides with molecular weights below 20,000 daltons. It is hypothesized that the protein gradient comes about probably because lens crystallins are capable of making extensive surface contacts to produce a tightly packed matrix. As the lens ages, post-synthetic modifications and hydrolytic breakdown produce a gradual disorganization in these structural proteins. Local or general disorganization will allow water to fill the gaps and produce hydration, which could predispose the lens to opacity formation.