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Abstract #108603 Published in IGR 23-4
Association between HSP-Specific T-Cell Counts and Retinal Nerve Fiber Layer Thickness in Patients with Primary Open-Angle Glaucoma
Saini C; Jiang S; Devlin J; Pan L; Tang Y; Tang J; Sun JA; Lorenzo MM; Wang Q; Pasquale LR; Cho KS; Chen DF; Shen LQOphthalmology science 2023; 3: 100310
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 () 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 ( = 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%, = 0.004; 5.8 ± 2.7% vs. 1.8 ± 1.3%, < 0.001; 13.2 ± 13.3 vs. 4.3 ± 5.2, = 0.01; respectively), but similar Treg specific for the same HSPs compared with controls ( ≥ 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; < 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 = -0.31, = 0.03; = -0.52, p = 0.002; = -0.72, < 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.
Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts.
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