Previous studies of both human
1-6 and nonhuman primate
7 optic nerves have generally found that there are fewer axons in the eyes of older individuals. In one of the first of such studies, Dolman et al.
1 reported qualitatively that there seemed to be a diminished density of axons in the optic nerves of humans beyond 60 years of age. Then, using manual quantification techniques in a study of 16 human eyes, Balazsi et al.
2 reported a rate of decline of 5637 axons per year of age (about 0.32% per year of the intercept). Shortly thereafter, Johnson et al.
3 used a computerized image analysis technique to quantify axon numbers in 13 optic nerves from 11 human cadavers and reported a slightly higher rate of 7554 fewer axons per year of age (or ∼ −0.51% of their intercept value). Mikelberg et al.
5 also used a computerized technique to re-evaluate 12 of the optic nerves from their original study
2 of 16, limiting this newer study to only those samples with the most adequate tissue preservation, and found a rate similar to their earlier report (4909 fewer axons per year, or −0.37% of their intercept value). In a larger study, Jonas et al.
6 also found a similar rate of axon loss with increasing age (5426 fewer axons per year, or −0.5% of the intercept,
N = 22). In contrast, Repka and Quigley
4 applied strict inclusion criteria and found a substantially lower rate of loss (only 534 fewer axons per year, or < −0.1% of their intercept value,
N = 19). Though the apparent rate of axon loss with increasing age was generally consistent across five of these six studies, it was significantly different from zero in only one of them,
6 which underscores the fact that the rate derived from cross-sectional studies is generally shallow and difficult to determine given the wide range of variability across the human population at any age.
4 This point was also made explicitly by Morrison and colleagues
7 in their study of 28 rhesus monkeys. In that study, Morrison et al.
7 estimated the rate of axon loss to be 4531 fewer axons per year (or −0.4% of their intercept value) from the monkey optic nerve, which also happened to be not significantly different from zero.
7 Since the lifespan of the monkey is approximately one-third that of human, Morrison et al.
7 calculated that the equivalent rate for human eyes would be approximately1440 fewer axons per year of age, which is substantially lower than the rate reported by most of the other studies on human optic nerves (except Repka and Quigley
4 ). Sandell and Peters
8 also compared a group of six very old rhesus monkeys (average age of 31 years) with a group of seven young monkeys (average age of 7 years) and found a reduction of greater than 44% optic nerve axons in the older animals.