Altered High-Density Lipoprotein Expression Pattern in the Aqueous Humor From Eyes With Age-Related Macular...

Area of Science:

• Ophthalmology
• Proteomics
• Biochemistry

Background:

• Age-related macular degeneration (AMD) involves altered protein expression in aqueous humor (AH).
• Neovascular AMD (nAMD) and non-neovascular AMD (nnAMD) represent distinct stages of the disease.
• Understanding proteomic differences can elucidate disease mechanisms.

Purpose of the Study:

• To conduct an unbiased proteomic analysis of aqueous humor (AH).
• To identify proteomic signatures differentiating neovascular AMD (nAMD) and non-neovascular AMD (nnAMD) stages.
• To explore the relationship between serum and ocular high-density lipoprotein (HDL) levels.

Main Methods:

• Aqueous humor samples were collected from nAMD (n=39), nnAMD (n=30), and healthy control (n=36) eyes.
• Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for proteomic analysis.
• Differentially expressed proteins underwent functional analysis, and correlations with serum HDL-C were assessed.

Main Results:

• Seventeen proteins were upregulated and five downregulated in nAMD versus controls; enriched pathways included complement and HDL particle pathways.
• Forty-six proteins were upregulated in nAMD versus nnAMD; enriched pathways included HDL particle and complement.
• No significant protein differences were observed between nnAMD and control eyes.
• Upregulated HDL proteins (ApoA-I, ApoA-II, PON1) in nAMD showed negative correlation with serum HDL-C.

Conclusions:

• HDL-associated proteins are upregulated in the aqueous humor of nAMD eyes.
• This upregulation is independent of serum HDL-C levels.
• Serum HDL-C may not accurately reflect ocular HDL particle levels in nAMD, suggesting retinal lipid dysregulation.