Age-related Changes in Human RPE Cell Density and Apoptosis Proportion in Situ

Purpose: To determine the effect of age on the proportion of apoptotic cells in the RPE and cellular density in human eyes in situ.

Methods: RPE flatmounts prepared from 22 adult human cadaver eyes (11 pairs; ages 19-87) were stained for apoptotic cells by a TUNEL technique. The density of RPE cells was also measured. The flatmount was divided into four concentric regions centered on the fovea (zone 1, 0-1.5 mm radius; zone 2, 1.5-3.0 mm; zone 3, 3.0-12.5 mm; and zone 4, >12.5 mm).

Results: There was a positive correlation between the donor's age and the proportion of apoptotic RPE cells per eye (r = 0.63; P = 0.04), which increased during the sixth decade and was higher in older (age range, 56-87 years) than in younger (age range, 19-48 years) eyes (0.56 +/- 0.14 vs. 0.07 +/- 0.07 cells per 100,000 cells, respectively; P = 0.03). Apoptotic RPE cells were located mainly in zone 1 in older eyes. Cell density decreased in the RPE as the distance from the fovea increased (r = 0.66, P < 0.05). The decrease was most prominent in zone 4 (r = -0.76, P = 0.007).

Conclusions: The proportion of apoptotic human RPE increased significantly with age. Apoptotic RPE cells are confined mainly to the macula of older human eyes. The observation that RPE cell death occurs in the macula but the density of RPE cells remains unchanged in the macula and decreases in the periphery suggests that migration of peripheral RPE cells may compensate for the death of macular RPE cells.