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San Diego, CA – January 2025
A groundbreaking study from the University of California San Diego has unveiled a U-shaped relationship between high-density lipoprotein (HDL) levels and the risk of age-related macular degeneration (AMD), a leading cause of blindness among older adults in industrialized nations. Researchers found that individuals with HDL levels in the middle range had the lowest risk, while those with either low or high HDL levels experienced a significantly increased likelihood of developing AMD.
The study, published in the journal Ophthalmology, also identified genetic factors associated with HDL metabolism as contributors to AMD risk. Specific gene variants, such as those in the ABCA1 and LIPC genes, were found to be protective, while a newly implicated gene, LPA, emerged as a potential risk factor.
AMD and Lipid Metabolism: A Complex Connection
AMD is characterized by the accumulation of drusen—lipoprotein-rich deposits—in the retina, leading to progressive vision loss. While prior studies have suggested a link between lipid metabolism and AMD, conflicting results left many questions unanswered. This latest research provides new insights by analyzing clinical and genetic data from 7,356 participants enrolled in the National Institutes of Health’s All of Us Research Program.
The study included 2,328 AMD patients and 5,028 controls matched by age, race, and gender. Researchers evaluated participants’ smoking status, history of hyperlipidemia, statin use, and laboratory measures of lipid levels, such as LDL, HDL, and triglycerides. Genetic analyses focused on single nucleotide polymorphisms (SNPs) related to HDL and LDL metabolism.
Key Findings
- Both low and high HDL levels were significantly associated with increased AMD risk, forming a U-shaped curve.
- Smoking and statin use were identified as additional risk factors.
- No significant relationship was found between AMD and LDL or triglyceride levels.
- Variants in the ABCA1 and LIPC genes were protective against AMD, while the LPA gene, linked to lipoprotein(a), emerged as a novel risk factor potentially involved in drusen formation.
Implications for Prevention and Treatment
The discovery of a U-shaped relationship between HDL levels and AMD risk underscores the importance of balanced lipid levels for eye health. Additionally, the identification of the LPA gene opens new avenues for understanding drusen formation and potential lipid-targeted therapies for AMD prevention and treatment.
“These findings suggest that HDL metabolism plays a complex role in AMD pathogenesis,” said Dr. Jimmy S. Chen, the study’s lead author. “Future research should explore the mechanisms behind these associations and evaluate lipid-modulating therapies as potential interventions.”
Study Limitations and Future Directions
While the study provides valuable insights, it relies on retrospective data and diagnostic codes, limiting the analysis of AMD severity. The researchers recommend prospective studies to validate these findings and further investigate the role of the LPA gene and other genetic factors in AMD.
Reference:
Jimmy S. Chen et al., High Density Lipoproteins Associate with Age-Related Macular Degeneration in the All of Us Research Program, Ophthalmology (2025). DOI: 10.1016/j.ophtha.2024.12.039
