Abstract
Purpose:
Oxidative stress is suggested as a cause of age related macular degeneration (AMD) but evidence that stress is occurring in the major pathogenic target of AMD, the retinal pigment epithelium (RPE), is lacking. Mitochondrial elongation is a morphological change caused by metabolic stress. Mitochondria are dynamic organelles continuously undergoing fusion and fission. The balance between these opposing processes shapes the mitochondria and reflects the metabolic status of a cell. With stress produced by starvation and/or increases in reactive oxygen species (ROS), mitochondria elongate, perhaps as an attempt to increase energy production. We measured the number and length of mitochondria in the macula RPE of young and old rhesus monkeys as a potential marker of metabolic stress.
Methods:
Eyes of seven monkeys (Macaca mulatta), 1, 2, 6.5, 24, 24, 26, and 35 years of age, were studied by electron microscopy. The number and length of mitochondria were measured in macula RPE. Measurements were assessed separately for the basal, middle and apical regions of the RPE cell. Because mitochondria are concentrated in the basal third of the cell, we use the basal measurements for comparisons of mitochondrial number and length versus age.
Results:
Except for a high in the youngest and a low in the oldest, mitochondrial number remained similar for most of the lifespan of the monkeys, the latter similar to results of Feher et al. (2006) for human RPE. An average length of mitochondria, however, increased with age. Some of these mitochondria became extremely long, 4-5 microns in length, and tended to appear in clusters.
Conclusions:
Elongation of mitochondria with age in the macular RPE of monkeys suggests that metabolic stress occurs and is increasing with age, consistent with the contribution of oxidative stress to AMD. It would be interesting to know if similar changes occur in non-macula RPE and if there is an association in monkeys that develop AMD versus those that do not.
Keywords: 412 age-related macular degeneration •
600 mitochondria •
701 retinal pigment epithelium