Date Published:
2023 Sep
Abstract:
OBJECTIVE: Previous laboratory reports implicate heat shock protein (HSP)-specific T-cell responses in glaucoma pathogenesis; here, we aimed to provide direct clinical evidence by correlating systemic HSP-specific T-cell levels with glaucoma severity in patients with primary open-angle glaucoma (POAG). DESIGN: Cross-sectional case-control study. SUBJECTS: Thirty-two adult patients with POAG and 38 controls underwent blood draw and optic nerve imaging. METHODS: Peripheral blood monocytes (PBMC) were stimulated in culture with HSP27, α-crystallin, a member of the small HSP family, or HSP60. Both interferon-γ (IFN-γ)+ CD4+ T helper type 1 cells (Th1) and transforming growth factor-β1 (TGF-β1)+ CD4+ regulatory T cells (Treg) were quantified by flow cytometry and presented as a percentage of total PBMC counts. Relevant cytokines were measured using enzyme-linked immunosorbent assays. Retinal nerve fiber layer thickness (RNFLT) was measured with OCT. Pearson's correlation (
r) was used to assess correlations. MAIN OUTCOME MEASURES: Correlations of HSP-specific T-cell counts, and serum levels of corresponding cytokine levels with RNFLT. RESULTS: Patients with POAG (visual field mean deviation, -4.7 ± 4.0 dB) and controls were similar in age, gender, and body mass index. Moreover, 46.9% of POAG and 60.0% of control subjects had prior cataract surgery (
P = 0.48). Although no significant difference in total nonstimulated CD4+ Th1 or Treg cells was detected, patients with POAG exhibited significantly higher frequencies of Th1 cells specific for HSP27, α-crystallin, or HSP60 than controls (7.3 ± 7.9% vs. 2.6 ± 2.0%,
P = 0.004; 5.8 ± 2.7% vs. 1.8 ± 1.3%,
P < 0.001; 13.2 ± 13.3 vs. 4.3 ± 5.2,
P = 0.01; respectively), but similar Treg specific for the same HSPs compared with controls (
P ≥ 0.10 for all). Concordantly, the serum levels of IFN-γ were higher in POAG than in controls (36.2 ± 12.1 pg/ml vs. 10.0 ± 4.3 pg/ml;
P < 0.001), but TGF-β1 levels did not differ. Average RNFLT of both eyes negatively correlated with HSP27- and α-crystallin-specific Th1 cell counts, and IFN-γ levels in all subjects after adjusting for age (partial correlation coefficient
r = -0.31,
P = 0.03;
r = -0.52, p = 0.002;
r = -0.72,
P < 0.001, respectively). CONCLUSIONS: Higher levels of HSP-specific Th1 cells are associated with thinner RNFLT in patients with POAG and control subjects. The significant inverse relationship between systemic HSP-specific Th1 cell count and RNFLT supports the role of these T cells in glaucomatous neurodegeneration. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found after the references.
