Systemic and Local Lipids in Nonhuman Primates With Drusen and Age-Related Maculopathies

Area of Science:

• Ophthalmology
• Gerontology
• Metabolic Research

Background:

• Lipids are crucial in the pathology of age-related macular degeneration (AMD).
• Nonhuman primates (NHPs) exhibiting macular drusen offer a valuable model for studying AMD.
• Understanding lipid involvement in AMD pathogenesis is essential for developing effective treatments.

Purpose of the Study:

• To investigate the characteristics of drusen and associated lipid profiles in aged nonhuman primates.
• To compare extracellular and intracellular lipid deposits in NHP macular disease models.
• To explore the relationship between systemic metabolic factors and retinal lipid accumulation in NHPs.

Main Methods:

• Fundus photography, optical coherence tomography (OCT), and fundus autofluorescence were used to evaluate aged rhesus macaques.
• Plasma glucose, lipid profiles (cholesterol, LDL, HDL, triglycerides), and apolipoproteins (ApoA1, B, CIII, E) were measured.
• Retinal tissues underwent electron microscopy and immunostaining for lipids and apolipoproteins.

Main Results:

• 25 out of 203 macaques had soft drusen (extracellular sub-RPE deposits), increasing with age.
• 59 macaques had punctate dots (mostly hyperautofluorescent, no RPE elevation), associated with age, higher glucose, LDL, and ApoB.
• Ultrastructural analysis revealed extracellular lipid particles in drusen and intracellular lipid vacuoles in RPE cells for punctate dots.

Conclusions:

• Soft drusen in rhesus macaques represent extracellular lipid deposits linked to aging.
• Punctate dots are intracellular lipid accumulations associated with age, hyperglycemia, and hyperlipidemia.
• These findings suggest distinct lipid dysregulation mechanisms in NHP models of AMD.