Abstract
Purpose: :
To determine the presence of ligands to the receptor for advanced glycation end products (RAGE) in photoreceptors, retinal pigment epithelium (RPE) and drusen of humans and monkeys with age related drusenoid maculopathy
Methods: :
The macula area of the retina of a human subject with drusen and a 23 year old monkey with drusenoid maculopathy were examined by immune-fluorescent labeling using antibodies to the RAGE ligands, S100, belonging to a super family of EF calcium binding proteins, and HBGM1, a high motility box 1 nuclear protein.
Results: :
S100 expression was concentrated in Müller cells in the neural retina and in local areas of the RPE but especially in the RPE adjacent to drusen where it was most prominent at the basal side of the cell. HMGB1 was found in the nuclei of all cell types in the neural retina and weakly in the inner segments of photoreceptors. It labeled the nuclei of the RPE and occasionally revealed apically displaced nuclei at the dome of drusen, but there was no labeling of the non-nuclear structures. These ligands were not present in drusen. This pattern was identical in the human and monkey specimens.
Conclusions: :
The RAGE ligand S100 appears in RPE cells especially in those cells adjacent to drusen. Its tendency to be especially concentrated at the basal region of the cell where virtually all the mitochondria are located and where there is electron microscopic evidence of early RPE degeneration, suggests the presence of oxidative damage and/or inflammation. The similarity of the pattern in human and monkey retinas implies that age related maculopathy has similar disease processes in both species.
Keywords: age-related macular degeneration • drusen • microscopy: light/fluorescence/immunohistochemistry