Peripheral monocytes but not large high-density lipoprotein might contribute to chronic inflammation in patients with neovascular age-related macular degeneration

Abstract

Purpose : Chronic inflammation is one of the major characteristics of age-related macular degeneration (AMD). Both high-density lipoprotein (HDL) and monocytes influence local and systemic inflammation. Epidemiological studies demonstrated an association between elevated plasma levels of large HDL (L-HDL) and AMD; a relation with monocytes is less clear. We hypothesized that L-HDL in AMD patients has impaired anti-inflammatory function, while monocytes are tuned in a pro-inflammatory manner, thus facilitating disease progression.

Methods : We collected fresh blood from 20 patients with neovascular AMD (nAMD) (40.0% women; mean age (SD) 81.2 (5.7) yrs) and 20 age-similar controls (45.0% women; mean age (SD) 74.3 (4.3) yrs). We compared blood monocyte counts and signatures of 14 cell surface markers indicative of an inflammatory state using flow cytometry. Also, L-HDL samples isolated from plasma using two-step iodixanol gradient ultracentrifugation were tested for anti-inflammatory function on lipopolysaccharide (LPS)-activated monocytes from 3 blood bank donors. Markers generally associated with pro-inflammatory (CD14, CD36, CD54, CD62L, HLA-DR) and anti-inflammatory (CD200R, CD163, CD206) activation of monocytes were analyzed using flow cytometry.

Results : Compared to healthy controls, nAMD patients showed higher absolute counts of total monocytes (increased 16.4%, p<0.01), classical monocytes (14.7%, p<0.05), intermediate monocytes (143.9%, p<0.0001) and non-classical monocytes (77.4%, p<0.001). Compared to healthy controls, classical monocytes from nAMD patients showed significantly higher expression levels of pro-inflammatory markers including HLA-DR (47.9%, p<0.01), CD14 (26.4%, p<0.05) and lower expression levels of anti-inflammatory markers including CD200R (28.4%, p<0.05), CD163 (16.9%, p<0.05) and CD206 (12.8%, p<0.01). We found no differences in modulation of inflammatory phenotype of LPS-activated monocytes by L-HDL isolated from nAMD patients vs. age-similar controls.

Conclusions : Our data show no differences in anti-inflammatory function of L-HDL from nAMD patients, but indicate that their monocytes have an increased inflammatory profile compared to healthy controls. Therefore, monocytes with increased pro-inflammatory function might contribute to chronic non-resolving inflammation in AMD patients.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.