Abstract
Purpose:
Sub-RPE deposits such as drusen are widely accepted as precursors to age-related macular degeneration (AMD), although the mechanism(s) of their development and exact relationship to AMD remain to be elucidated. We recently discovered that sub-RPE deposits in aging human retina contain microscopic (0.3 - 20 µm) spherules of hydroxyapatite (HAP), the mineral form of calcium phosphate found in bone and teeth; and that these spherules are coated with proteins enriched in drusen such as complement factor H, amyloid beta, and vitronectin. Aging Rhesus and Japanese macaques also develop drusen similar to those in humans. Here, we examined whether drusen in the aging macaques also contain HAP deposits, and compared these to the HAP spherules found in humans. <br />
Methods:
We used multiple HAP-specific fluorescent dyes to stain post-mortem fixed retinal slices and flatmounts from male and female Japanese and Rhesus macaques of ages ranging from 16 to 38 years in which drusen had been documented by fundus photography in vivo. They were imaged by confocal fluorescence and brightfield microscopy, which were compared to color fundus photographs collected in vivo.<br />
Results:
Drusen in aged macaque retinas were confirmed by brightfield and autofluorescence microscopy. Multiple drusen from both sexes and species stained positive for HAP, but in comparison to humans the deposits were generally smaller and more amorphous in form, without distinguishable shell-like appearance. Older retinas generally had more drusen, all of which exhibited HAP-positive staining.<br />
Conclusions:
We conclude that drusen in the two macaque species and humans contain HAP deposits that share important similarities as well as some differences. The smaller size and differing morphology of the macaque HAP deposits compared with the hollow spherules in humans suggest clear differences in how the these deposits are nucleated and their ability to grow.