Fundamental differences in patterns of retinal ageing between primates and mice

Area of Science:

• Ophthalmology
• Neuroscience
• Cell Biology

Background:

• Photoreceptors have high metabolic demands and age, leading to vision loss.
• Rod and cone photoreceptor aging differs between species, with primates retaining cones but experiencing functional decline.

Purpose of the Study:

• To investigate the cellular mechanisms of cone photoreceptor aging in primates.
• To compare primate and mouse retinal aging processes.
• To identify potential targets for restoring visual function in aged primates.

Main Methods:

• Examination of aged primate retinae.
• Analysis of cellular stress markers, inflammation, and amyloid beta deposition.
• Measurement of adenosine triphosphate (ATP) levels and cytochrome c oxidase activity.
• Assessment of mitochondrial positioning and glycolytic activity in cone photoreceptors.

Main Results:

• Aged primate retinae exhibit elevated stress but low inflammation, with no amyloid beta deposition.
• A significant reduction (>70%) in ATP and decreased cytochrome c oxidase were observed in aged primates.
• Cone photoreceptors showed altered mitochondrial positioning and increased glycolytic activity.
• Bruch's membrane thickened in aged primates, distinct from aging mice.

Conclusions:

• Reduced ATP levels likely contribute to cone functional decline in aging primates.
• The retention of cones in aged primates offers a potential window for functional restoration through improved cellular energy supply.
• Differences in aging pathways between primates and mice, particularly regarding inflammation and amyloid beta, challenge current therapeutic strategies for retinal aging and macular degeneration.