The search for a solution to senile cataracts. Proctor lecture.

Abstract

The mature lens is unique in that except for a peripheral ring of active metabolizing tissue, damaged macromolecules can not be replaced and metabolic cycles are inoperative. This situation is a result of a remarkable process. New fibers arising from the epithelial cells in the equatorial region gradually lose their nuclei and their DNA and RNA (Fig. 1). Thus the inner region of the lens is dependent on the outer tissue to maintain homeostatic control and to metabolize toxic compounds. This arrangement makes a substantial portion of the lens tissue particularly vulnerable to damage since no apparent mechanism is available for repair. The lens can be considered to be in a metastable state. It has a remarkably high protein content, for the human lens, approximately 35% on a wet weight basis. In the inner region, the nucleus, of the rat lens, the protein concentration may be as high as 65-70%! Of course, in spite or because of this unique protein concentration, the tissue is transparent, not translucent but dramatically transparent in the wave length region beyond the range of protein absorption. Such observation suggests a uniformity of refractive index throughout the lens indicative of short range spatial order as recently reported by Delaye and Tardieu. With aging there is deterioration of this remarkable architecture which is not sufficient to cause blindness but leads to a definitive loss of transparency. Changes in protein structure can be linked to this alteration in optical properties. First with aging there is an increased abundance of water insoluble protein—indeed our measurements suggest that after the first few years of life, the water soluble protein fraction appears to remain relatively constant in abundance while there is an increasing accumulation of water insoluble protein (Fig. 2). There is more insoluble protein found in the inner