Protein Changes during Aging and the Effects of Long-Term Cortisol Treatment in Macaque Monkey Lens

Macaca nemestrina pig-tail macaques were administered daily oral doses of 3.85 or 5.78 mg/kg of cortisol for 1 year. The ages of the macaques were from 19 to 29 years. After 1 year, lenses were observed using a slitlamp ophthalmoscope and the stage of cataract was classified in each eye. Enucleated lenses were analyzed for content of soluble and insoluble proteins. Lens proteins were analyzed using SDS polyacrylamide gel electrophoresis (SDS-PAGE) and the changes in lens proteins were quantified using densitometry of the individual gels. Untreated control lenses were obtained over the range of 4 to 29 years of age and the proteins were analyzed. A slow progressive increase in the cataract stage and in the proportion of insoluble protein aggregates corresponded with the animal age, not the cortisol treatment. The observed changes in the protein components may suggest an important role for cytoskeletal proteins in lens transparency during aging. Exposure to high doses of oral steroids over a period of 1 year did not result in detectable modification of crystallin or cytoskeletal proteins. Even at high doses, longer exposure may be necessary to produce the cataract associated with steroid administration.