Serum cholesterol efflux capacity underpins early AMD

Patients with early age-related macular degeneration (eAMD) appear to have increased serum cholesterol efflux capacity, according to a recent Singapore study. The same is true for polypoidal choroidal vasculopathy (PCV), but not for typical neovascular AMD (tAMD).

The case-control analysis included 80 patients with eAMD (mean age 67.1 years, 58.8 percent men) and 212 with neovascular AMD (nAMD). In the latter subgroup, 80 were diagnosed with tAMD (mean age 69.4 years, 60.0 percent men) and 132 with PCV (mean age 68.3 years, 59.1 percent men). A parallel group of age- and sex-matched controls (mean age 66.7 years, 52.7 percent men) was also included.

Serum cholesterol efflux capacity, defined as the capacity of a person’s serum to accept cholesterol, was measured using in vitro cell assays, while nuclear magnetic resonance was used to quantify lipoprotein subfractions. A total of 402 serum samples were included in the analysis.

After adjusting for age, sex, and the use of lipid-lowering medications, eAMD and nAMD patients showed a mean cholesterol efflux capacity of 68.0 percent and 75.93 percent, respectively. Both readings were significantly higher than the control average, which was 56.9 percent (p<0.0083). [Ophthalmol Sci 2022;doi:2:100142]

Stratifying according to nAMD subtype revealed that only PCV patients had significantly higher average serum cholesterol efflux capacity than controls (85.3 percent; p<0.0083). Those with tAMD had a mean value of 60.5 percent, which was statistically comparable to that in controls.

“A surprising finding in our study was that although the cholesterol efflux capacity was higher in participants with eAMD and PCV, it was not in those with tAMD,” the researchers said. “Probably the main element to be considered is that the lipid accumulation beneath the retinal pigment epithelium is a life-long process.”

Meanwhile, serum cholesterol efflux capacity captures the functionality of a patient’s high-density lipoprotein (HDL) when already afflicted by AMD. “Local cholesterol transport and efflux in the eye also may be subject to different and more complex regulation than systemic cholesterol efflux,” the researchers added.

The role of HDL

Data from nuclear magnetic resonance additionally showed that the mean diameter of HDL cholesterol was significantly larger in patients with eAMD and PCV, as compared with controls (9.96 and 9.97 vs 9.84 mm; p=0.0001 for both). No such interaction was reported for tAMD participants.

Pearson correlation analysis also revealed that levels of HDL, stratified according to size, were moderately but significantly associated with cholesterol efflux capacity. For instance, HDL of sizes 7.8–8.2 nm (R, 0.235) and 8.2–8.8 nm (R, 0.229; p<0.001 for both) both showed positive interaction with efflux capacity. The same was true for apolipoprotein A1 levels (R, 0.224; p<0.001).

Of the 28 subfractions of HDL, most of the small, medium, and large HDLs were also associated with efflux capacity, an effect that was absent in all seven extra-large HDL fractions.

“Our results indicate that small, medium, and large HDLs among all lipids play important roles in the pathogenesis of eAMD and PCV,” the researchers said, adding that the present findings contribute to the growing knowledge around the diverse role that lipoproteins play in AMD.

“Further studies are needed to assess completely the diverse biological activities of HDL in AMD, including macular pigment transport, regulation of inflammation, and the local cholesterol transport system,” they noted.