RANTES (CCL5) in Patients With Geographic Atrophy Age-Related Macular Degeneration

Abstract

Purpose A previous study from our research group showed significantly lower levels of RANTES (Regulated upon Activation, Normal T Cell Expressed and Secreted) in patients with intermediate age-related macular degeneration (AMD) compared to control patients with no AMD. The primary aim of this study was to assess levels of RANTES in a cohort of patients with a more advanced form of the disease, geographic atrophy (GA), in comparison with controls. Methods The study was conducted on a cohort of patients with GA recruited into a Colorado AMD registry. Cases and controls were defined with multimodal imaging. Plasma levels of the chemokine RANTES were measured using a multiplex assay. A nonparametric (rank-based) regression model was fit to RANTES with a sex by AMD category interaction. Results The plasma levels of RANTES were significantly higher in the control group in comparison to the GA AMD group (median [interquartile range]): 10,204 [5799–19,554] pg/mL vs. 5435 [3420–9177] pg/mL, respectively, P < 0.01). When moderated by sex, there was no statistical difference between the male and female GA AMD or the male and female controls. Conclusions We found lower level of RANTES in patients with GA AMD compared with controls. This finding is consistent with the findings from our previous intermediate AMD study. However, in contrast to the results of our previous research, when moderated by sex there was no statistical difference between male and female GA patients. Translational Relevance The biomarker RANTES is significantly lower in GA AMD patients compared to controls.

Interleukin-4 Plasma Levels Stratified by Sex in Intermediate Age-Related Macular Degeneration and Geographic Atrophy

“…The inclusion and exclusion criteria and informed consent are described in detail elsewhere. 18 , 19 , 22 In summary, inclusion criteria for case subjects included in the registry are aged between 55 and 99 years, unilateral or bilateral AMD, and capacity for informed consent. Exclusion criteria include: branch and central retinal vein occlusion with severe macular damage, pan-retinal photocoagulation or anti-VEGF injections for diabetic retinopathy, active ocular inflammatory disease, treatment with select immunosuppressives, serious mental health or terminal illnesses, and a decrease in visual acuity secondary to a severe pre-existing retinal disease except AMD.…”

“… 14 – 16 The overarching hypothesis for our research is that systemic inflammation contributes to local ocular events in AMD and identification of systemic biomarkers may lead to earlier diagnosis and targeted therapies to prevent further visual damage. In research to date, we have demonstrated a significant role for systemic inflammatory markers, specifically cytokines, 14 , 16 chemokines, 17 – 19 and complement factors, 20 – 22 with sex-specific modulation of the complement system 22 and RANTES 18 , 19 in AMD.…”