Abstract
Abstract: :
Purpose: While examining the retinas of RPE65-/- mice in RPE transplant experiments, unusual changes at the base of the RPE layer were observed in aging RPE65 -/- mice, which we here compare to normal mice of similar age. Methods: Retinas from young and old mice were examined by electron microscopy. Results: In young mice from both strains, the basal surface of the RPE layer is normal, containing numerous mitochondria, basal in-folding of the plasma membrane and a thin basal lamina. At 6-8 months of age, vacuoles develop within the RPE of RPE65-/- but not normal mice. The vacuoles reflect backed up retinyl esters (Redmond et al. Nat Genet 20:344, 1998). At this time, we also find increased thickness of the basal lamina in the mutant. At 10 to 16 months, changes at the base and basal lamina of the RPE65-/- RPE layer become more striking. There is a loss of mitochondria and reduced in-folding. A basal lamina-like structure increases to 5-10 times its width and protrudes into the basal membrane in a columnar fashion forming pockets of cytoplasm, some virtually disconnected from the main cell body and nucleus, resembling drusen formation in aging human and primate retina. Only a slight suggestion of this change is seen in RPE of normal mice. Conclusion: The basal surface of the RPE layer in the aging RPE65-/- mouse shows a senescent transformation that resembles drusenoid degeneration, occurring with minimum lipofuscin accumulation (Katz & Redmond, IOVS 42:3023, 2001). It may be related to a degeneration of the RPE cell from excessive retinoid buildup.
Keywords: 567 retinal pigment epithelium • 561 retinal degenerations: cell biology • 309 aging