TY - JOUR

T1 - Chemokine Receptor Profile of T Cells and Progression Rate of Geographic Atrophy Secondary to Age-related Macular Degeneration

AU - Martinez Villarruel Hinnerskov, Jenni

AU - Krogh Nielsen, Marie

AU - Kai Thomsen, Alexander

AU - Steffensen, Maria Abildgaard

AU - Honoré, Bent

AU - Vorum, Henrik

AU - Nissen, Mogens Holst

AU - Sørensen, Torben Lykke

PY - 2024/1/2

Y1 - 2024/1/2

N2 - PURPOSE: Geographic atrophy (GA) secondary to age-related macular degeneration is a progressive retinal degenerative disease. Systemic chemokine receptors and known risk-associated single-nucleotide polymorphisms have been associated with GA pathogenesis. Because halting progression is pivotal for patients, we investigated the association of candidate chemokine receptors and progression rate (PR) of atrophic lesions in patients with GA.METHODS: This prospective observational study conducted at a single center included 85 patients with GA and 45 healthy controls. Patients were followed up after 13 months on average. Serial fundus autofluorescence images were used to determine the PR of atrophic lesions. The proportion of chemokine receptors on peripheral lymphocytes were determined by flow cytometric analysis.RESULTS: Patients with GA had a lower proportion of CCR6 on CD8+T cells compared to healthy controls. Importantly, the proportion of CCR6 on CD4+T cells was lower in patients with fast GA progression compared to patients with slow progression of disease, suggesting that dysregulation of CCR6 could be involved in progression of GA. We also found that GA patients had a markedly higher percentage of CCR5 on CD4+ and CD8+T cells compared to healthy controls. After stratification according to ARMS2 polymorphism, we found a significantly lower level of CCR5 on CD8+T cells among patients with high-risk genotypes compared with patients with the low-risk genotype.CONCLUSIONS: Our study finds that chemokine receptors are dysregulated in patients with GA and that CCR6 might be involved in GA progression, making it a potential target for intervention.

AB - PURPOSE: Geographic atrophy (GA) secondary to age-related macular degeneration is a progressive retinal degenerative disease. Systemic chemokine receptors and known risk-associated single-nucleotide polymorphisms have been associated with GA pathogenesis. Because halting progression is pivotal for patients, we investigated the association of candidate chemokine receptors and progression rate (PR) of atrophic lesions in patients with GA.METHODS: This prospective observational study conducted at a single center included 85 patients with GA and 45 healthy controls. Patients were followed up after 13 months on average. Serial fundus autofluorescence images were used to determine the PR of atrophic lesions. The proportion of chemokine receptors on peripheral lymphocytes were determined by flow cytometric analysis.RESULTS: Patients with GA had a lower proportion of CCR6 on CD8+T cells compared to healthy controls. Importantly, the proportion of CCR6 on CD4+T cells was lower in patients with fast GA progression compared to patients with slow progression of disease, suggesting that dysregulation of CCR6 could be involved in progression of GA. We also found that GA patients had a markedly higher percentage of CCR5 on CD4+ and CD8+T cells compared to healthy controls. After stratification according to ARMS2 polymorphism, we found a significantly lower level of CCR5 on CD8+T cells among patients with high-risk genotypes compared with patients with the low-risk genotype.CONCLUSIONS: Our study finds that chemokine receptors are dysregulated in patients with GA and that CCR6 might be involved in GA progression, making it a potential target for intervention.

U2 - 10.1167/iovs.65.1.5

DO - 10.1167/iovs.65.1.5

M3 - Journal article

C2 - 38165703

VL - 65

SP - 5

JO - Investigative Ophthalmology & Visual Science (Online)

JF - Investigative Ophthalmology & Visual Science (Online)

SN - 1552-5783

IS - 1

ER -