CYTOCHROME-OXIDASE ACTIVITY IN BOVINE AND HUMAN RETINAL-PIGMENT EPITHELIUM - TOPOGRAPHICAL AND AGE-RELATED DIFFERENCES

Cytochrome c oxidase (CO) is a mitochondrial enzyme complex that was used in this study as a marker enzyme of aerobic metabolism. The activity of the enzyme was measured in the RPE of posterior and peripheral regions of bovine and human eyes. The posterior regions included the bovine area centralis or human macula. To determine if aging affected CO activity, activity was compared in RPE cells from human donors of varying age. An in vitro aging model was also used in which CO activity was measured in bovine and human RPE cells that were aged by repeated culture passage. CO activity was found to be significantly lower in posterior RPE cells from both bovine and human eyes suggesting that aerobic metabolism in RPE cells differs regionally. For human RPE samples, CO activity was lower in posterior cells at all donor ages and no significant age-related changes in CO activity were observed except that the highest activity samples were from older donors. Similarly, RPE cells that were aged in culture showed no significant changes in CO activity per cell although there were some high activity samples among the aged cultures. With aging, RPE cell density at confluency declined resulting in lower total CO activity in the aged epithelial monolayer. The data suggest that the ability of individual RPE cells to generate energy via respiration is maintained in the aged eye, but because RPE cell number declines with age and the activity of remaining RPE cells does not increase commensurately, there may declines in the ability of the aged pigment epithelium to perform tissue-level functions (e.g., transepithelial transport). Further, the aging macula may be preferentially at risk for falling below energy thresholds to sustain high energy-requiring cellular functions since macular RPE cells appear to have a reduced respiratory capacity relative to peripheral cells.