June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Plasma Concentrations of Anti-inflammatory Cytokines Stratified by Sex in Intermediate Age-Related Macular Degeneration and Geographic Atrophy
Author Affiliations & Notes
  • Vivian Rajeswaren
    Ophthalmology, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, United States
  • Brandie Wagner
    Ophthalmology, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, United States
    Colorado School of Public Health, Aurora, Colorado, United States
  • Alan G Palestine
    Ophthalmology, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, United States
  • Jennifer Patnaik
    Ophthalmology, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, United States
  • Maryam Ghiassi
    Ophthalmology, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, United States
  • Naresh Mandava
    Ophthalmology, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, United States
  • Marc T Mathias
    Ophthalmology, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, United States
  • Niranjan Manoharan
    Ophthalmology, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, United States
  • Talisa E de Carlo
    Ophthalmology, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, United States
  • Ramya Gnanaraj
    Ophthalmology, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, United States
  • Anne M Lynch
    Ophthalmology, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, United States
  • Footnotes
    Commercial Relationships   Vivian Rajeswaren None; Brandie Wagner None; Alan Palestine None; Jennifer Patnaik Orbis, Code C (Consultant/Contractor), GoCheckKids, Code C (Consultant/Contractor); Maryam Ghiassi None; Naresh Mandava Soma Logic, Code C (Consultant/Contractor), ONL Therapeutics, Code C (Consultant/Contractor), 2C Tech, Code I (Personal Financial Interest), Aurea Medical , Code I (Personal Financial Interest), Alcon, Code P (Patent), 2C Tech, Code P (Patent); Marc Mathias None; Niranjan Manoharan Iveric Bio, Code F (Financial Support); Talisa de Carlo None; Ramya Gnanaraj None; Anne Lynch None
  • Footnotes
    Support  National Eye Institute of the National Institutes of Health under award number R01EY032456 (AML),NIH/NCATS Colorado CTSA Grant Number UL1 TR002535, Greenwald Family research fund,Research to Prevent Blindness grant to the Department of Ophthalmology, University of Colorado, the Frederic C. Hamilton Macular Degeneration Center, Sue Anschutz-Rogers Eye Center Research Fund
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 1738. doi:
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    • Get Citation

      Vivian Rajeswaren, Brandie Wagner, Alan G Palestine, Jennifer Patnaik, Maryam Ghiassi, Naresh Mandava, Marc T Mathias, Niranjan Manoharan, Talisa E de Carlo, Ramya Gnanaraj, Anne M Lynch; Plasma Concentrations of Anti-inflammatory Cytokines Stratified by Sex in Intermediate Age-Related Macular Degeneration and Geographic Atrophy. Invest. Ophthalmol. Vis. Sci. 2023;64(8):1738.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Chronic local inflammation underlies the pathogenesis of Age-Related Macular Degeneration (AMD) leading to damage to the photoreceptors and retinal pigment epithelium. There is minimal research on the role of systemic inflammation particularly in the intermediate (iAMD) and Geographic Atrophy (GA) phenotypes of AMD. Recent research demonstrated decreased systemic levels of the anti-inflammatory cytokine IL-10 in GA. IL-10 is a well-characterized immunomodulatory cytokine interacting with several other cytokines including IL-4 and crucial for suppressing excess inflammation in immune-mediated pathologies. The purpose of this study was to investigate the role of IL-10 and IL-4 in a cohort of patients with iAMD and GA and to specifically: 1) Examine levels of IL-4 and IL-10 in patients with iAMD and GA compared to controls without AMD, 2) Determine if concentrations of these cytokines are moderated by sex.

Methods : We examined levels of IL-10 and IL-4 in cohorts of patients with iAMD and GA, and controls with no AMD recruited into the University of Colorado AMD registry from August 2014 to June 2021. Cases and controls were defined primarily by multimodal imaging. Cytokine levels were measured by multiplex immunoassay. A non-parametric rank based linear regression model was fit to plasma biomarkers with a sex by AMD category interaction.

Results : As shown in Table 1, we demonstrated a significant increase in IL-10 in the iAMD group compared to controls and a significant decrease in GA compared to the iAMD and control cohorts, p<0.01. IL-4 was significantly increased in GA compared to the iAMD and control groups, p<0.01. In table 2, female controls showed significantly decreased levels of IL-10 compared to male controls, p<0.01. Patterns of IL-4 and IL-10 were unchanged after stratifying by sex.

Conclusions : Our results indicate that increased plasma IL-4 in GA is not accompanied by upregulation of IL-10 when compared to iAMD, suggesting an impairment of immune down-regulation in GA. In addition, levels of these systemic biomarkers remained significantly different after stratifying by sex. These findings imply systemic modulation of IL-10 may serve as a novel targeted therapy for GA.

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

 

 

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