The phototoxicity of aged human retinal melanosomes
Bartosz Rózanowski1, Joyceline Cuenco, Sallyanne Davies
1School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK.
Abstract:
The purpose of this study was to determine whether an age-related increase in photoreactivity of human retinal melanosomes (MS) can cause phototoxicity to retinal pigment epithelium (RPE) cells. MS were isolated post mortem from young (20-30 years, young human melanosomes [YHMs]) and old (60-90 years, old human melanosomes [OHMs]) human eyes and from young bovine eyes (bovine melanosomes [BMs]). Confluent cultured ARPE-19 cells were fed equivalent numbers of OHMs or BMs and accumulated similar amounts of melanin as determined by electron paramagnetic resonance assay. Cells with and without MS were either maintained in the dark or exposed to blue light for up to 96 h and assessed for alterations in cell morphology, cell viability and lysosomal integrity. Incubation of cells in dark in the presence of internalized MS or irradiation of cells with blue light in the absence or presence of BMs did not significantly affect cell viability. However, exposures to blue light in the presence of OHMs resulted in abnormal cell morphology, up to approximately 75% decrease in mitochondrial activity, loss of lysosomal pH and cell death. OHMs contained significantly less melanin than YHMs, supporting the hypothesis that melanin undergoes degradation during RPE aging. Our results demonstrate that aged MS can be phototoxic to human RPE cells and support a contributing role of MS in RPE aging and in the pathogenesis of age-related macular degeneration.
Insights
Aged human melanosomes (MS) become phototoxic, causing retinal pigment epithelium (RPE) cell damage when exposed to blue light. This finding suggests a role for aged MS in RPE aging and age-related macular degeneration.
Area of Science:
- Ophthalmology
- Cell Biology
- Photobiology
Background:
- Melanosomes (MS) are melanin-containing organelles in retinal pigment epithelium (RPE) cells.
- Aging may alter MS properties, potentially impacting RPE function and health.
- Age-related macular degeneration (AMD) is a leading cause of vision loss, with RPE dysfunction as a key factor.
Purpose of the Study:
- To investigate if age-related changes in human melanosomes (MS) increase their photoreactivity and cause phototoxicity to retinal pigment epithelium (RPE) cells.
- To determine the role of aged MS in RPE cell damage and potential contribution to age-related macular degeneration (AMD).
Main Methods:
- Human melanosomes (MS) were isolated from young and old human eyes, and bovine eyes.
- Cultured RPE cells were exposed to blue light in the presence of different MS types.
- Cell viability, morphology, mitochondrial activity, and lysosomal integrity were assessed.
Main Results:
- Blue light exposure with aged human melanosomes (OHMs) caused significant RPE cell damage, including decreased mitochondrial activity and cell death.
- Young human melanosomes (YHMs) and bovine melanosomes (BMs) did not induce significant phototoxicity.
- Aged melanosomes contained less melanin, supporting melanin degradation during RPE aging.
Conclusions:
- Aged melanosomes (MS) exhibit phototoxicity towards human retinal pigment epithelium (RPE) cells.
- Phototoxic aged MS may contribute to RPE aging and the pathogenesis of age-related macular degeneration (AMD).
- Melanin degradation in aging MS could be a critical factor in RPE dysfunction.
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