The accumulation of lipofuscin in the retinal pigment epithelium (RPE) is dependent on the effectiveness of photoreceptor outer segment material degradation. This study explored the role of autophagy in the fate of RPE lipofuscin degradation. After seven days of feeding with either native or modified rod outer segments, ARPE-19 cells were treated with enhancers or inhibitors of autophagy and th...

Lipofuscin in the retinal pigment epithelium (RPE) is thought to be derived from phagocytosed photoreceptor outer segment disc membranes. Based on this hypothesis, one would predict that the rate of lipofuscin deposition in the RPE would be proportional to the density of photoreceptor cells in the retina. In previous studies it was demonstrated that specific loss of photoreceptor cells due to a...

Although the incomplete degradation of phagocytosed outer segment discs is thought to result in the formation of lipofuscin, there has to date been no proof of this concept. We report for the first time that cultured human retinal pigment epithelial (RPE) cells fed daily doses of isolated rod outer segments for periods of up to 3 months were capable of developing intracellular autofluorescent g...

PURPOSE To characterize the age-related accumulation of lipofuscin in a population of normal subjects, resolve differences in estimated accumulation rates obtained in previous studies, and characterize the spatial distribution of lipofuscin in the normal fundus. METHODS Spectrophotometric measurements were made at the fovea and 7 degrees temporal to the fovea in 145 normal subjects (age range...

A powerful technique currently used widely to track cells in the central nervous system is that of enhanced GFP as a fluorescent marker. Cells can be infected with a GFP-expressing retrovirus (1,2) or taken from GFP transgenic animals and transplanted into a syngeneic host (3). However, this approach may be confounded by considerable autofluorescence within the mammalian central nervous system....

There is shortage of extensive clinicopathologic studies of cellular senescence because the most reliable senescence biomarker, the detection of Senescence-Associated-beta-galactosidase activity (SA-β-gal), is inapplicable in archival material and requires snap-frozen tissues. We validated the histochemical Sudan-Black-B (SBB) specific stain of lipofuscin, an aggregate of oxidized proteins, lip...

Genes that increase susceptibility to age-related macular degeneration (AMD) have been identified; however, since many individuals carrying these risk alleles do not develop disease, other contributors are involved. One additional factor, long implicated in the pathogenesis of AMD, is the lipofuscin of retinal pigment epithelium (RPE). The fluorophores that constitute RPE lipofuscin also serve ...

The article ‘‘Lack of correlation between the spatial distribution of A2E and lipofuscin fluorescence in the human retinal pigment epithelium,’’ by Ablonczy and colleagues, forces us to re-evaluate 2 decades of dogma, and has potentially profound implications for the role (or lack thereof) of the bisretinoid A2E in human retinal degenerations. Using the elegant new method of imaging mass spectr...

PURPOSE Dietary supplementation with vitamin A is sometimes prescribed as a treatment for retinitis pigmentosa, a group of inherited retinal degenerations that cause progressive blindness. Loss-of-function mutations in the ABCA4 gene are responsible for a subset of recessive retinitis pigmentosa. Other mutant alleles of ABCA4 cause the related diseases, recessive cone-rod dystrophy, and recessi...

Optical measurements of the pigments of the retinal pigment epithelium (RPE) and choroid were made on 38 human autopsy eyes of both blacks and whites, varying in age between 2 wk and 90 yr old. Lipofuscin in melanin-bleached RPE was measured as fluorescence at 470 mm following excitation at 365 nm and was found to be proportional to fluorescence measured at 560 nm in unbleached tissue. Transmis...