T cell responses in human glaucoma

Abstract

Purpose : Resident glia in the retina and optic nerve play critical roles in the phenotype driving innate and adaptive immune responses in glaucoma. Present evidence from the analysis of human blood samples and isolated autoantibodies (along with the experimental studies of animal models using antigen immunization or adoptive transfer strategies) also supports the activation and pathogenic potential of adaptive immunity during glaucomatous neurodegeneration. This study aimed to explore the T cell-mediated component of adaptive immune responses through the analysis of T cell subset distribution in human glaucoma.

Methods : Blood samples were collected from 19 patients with glaucoma and 14 age- and gender-matched control subjects without glaucoma. Peripheral blood mononuclear cells were isolated from blood samples by Histopaque density gradient centrifugation. The isolated cells were then stained with fluorescence-labeled antibodies to T cell subsets and were analyzed by multicolor flow cytometry to calculate their percentage distribution. The helper T cell (Th) fractions were phenotyped based on the expression of CD4 and distinctive markers, such as IFN-γ (Th1), IL-4 (Th2), IL-17A (Th17), CD25 and FoxP3 (Treg). The analysis also included CD8+ cytotoxic T cells, and their CD25 and FoxP3 expressing Treg fractions.

Results : Analysis of T cell subset distribution detected a glaucoma-related shift. The CD4 to CD8 ratios were similar between glaucomatous or non-glaucomatous samples (p>0.05); however, glaucomatous samples exhibited a trend toward altered pattern of regulatory T cells, which was prominent by decreased ratios of CD4+/CD25+/FoxP3+ (CD4Treg) and CD8+/CD25+/FoxP3+ (CD8Treg) regulatory T cell populations relative to entire CD4+ or CD8+ populations, respectively (p<0.03).

Conclusions : This study detected T cell population shifts supporting the altered immune homeostasis toward autoimmunity in human glaucoma. More work of larger patient cohorts is needed to determine the effects of covariates, such as different types and stages of glaucoma, intraocular pressure levels, systemic diseases, and treatments. Continuing studies should also clarify whether the dysregulated T cell response may contribute to secondary neurodegenerative injury in glaucoma, or whether the altered T cell profile may serve as a diagnostic or prognostic biomarker of glaucoma for clinical predictions.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.