Translational vision science & technology · 2026
Left-Right Determination Factor 2 (LEFTY2) Is an Aqueous Humor Biomarker for Exfoliation Glaucoma.
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Smith Andrew J O, Sheybani Arsham, Greenwood Michael, Sieck Erin, Tsai Linda, Liu James, Siegfried Carla, Liu Ying, Shui Ying-Bo, Gonzalez Lilly, Stamer W Daniel, Bassnett Steven
Аннотация
PURPOSE: Exfoliation syndrome (XFS) is characterized by deposition of exfoliation material (XFM) in the anterior segment. XFM contributes to development of exfoliation glaucoma (XFG). Here, we evaluated left-right determination factor 2 (LEFTY2), a TGFβ superfamily protein, as an XFS and XFG biomarker.
METHODS: Aqueous humor (AH) and/or blood was collected from patients undergoing cataract surgery. Controls included patients with cataracts (CAT; AH, n = 78; blood, n = 20) or cataracts and primary open-angle glaucoma (CAT/GL; AH, n = 67; blood, n = 20). Affected groups included patients with cataracts and XFS (AH, n = 32; blood, n = 2) or cataracts and XFG (AH, n = 42; blood, n = 19). LEFTY2 concentration was measured by ELISA. To test if LEFTY2 is TGFβ responsive, human trabecular meshwork (HTM) cell cultures were treated with TGFβ1-3, and LEFTY2 expression was quantified by real-time quantitative PCR or ELISA.
RESULTS: AH LEFTY2 concentrations were significantly elevated in XFG patients (27.23 ± 45.39 ng/mL) versus controls (CAT: 1.19 ± 0.72 ng/mL, P < 0.0001; CAT/GL: 1.68 ± 1.81 ng/mL, P < 0.0001). ROC analyses indicated that LEFTY2 is a good AH biomarker for XFG (CAT vs. XFG, AUC = 0.87; P < 0.0001). LEFTY2 AH levels were highest in eyes judged to have the heaviest XFM deposits (ρ = 0.341, P = 0.0054). Plasma LEFTY2 levels did not correlate with disease status or ocular LEFTY2 levels. TGFβ treatment significantly increased LEFTY2 expression in HTM cells.
CONCLUSIONS: LEFTY2 is a promising AH biomarker for XFG. Its clinical value may be limited by accessibility, OD/OS discordance, and interpatient variability. Its role in XFG pathogenesis requires further study.
TRANSLATIONAL RELEVANCE: Identification of biomarkers for XFG may improve early detection and treatment.
METHODS: Aqueous humor (AH) and/or blood was collected from patients undergoing cataract surgery. Controls included patients with cataracts (CAT; AH, n = 78; blood, n = 20) or cataracts and primary open-angle glaucoma (CAT/GL; AH, n = 67; blood, n = 20). Affected groups included patients with cataracts and XFS (AH, n = 32; blood, n = 2) or cataracts and XFG (AH, n = 42; blood, n = 19). LEFTY2 concentration was measured by ELISA. To test if LEFTY2 is TGFβ responsive, human trabecular meshwork (HTM) cell cultures were treated with TGFβ1-3, and LEFTY2 expression was quantified by real-time quantitative PCR or ELISA.
RESULTS: AH LEFTY2 concentrations were significantly elevated in XFG patients (27.23 ± 45.39 ng/mL) versus controls (CAT: 1.19 ± 0.72 ng/mL, P < 0.0001; CAT/GL: 1.68 ± 1.81 ng/mL, P < 0.0001). ROC analyses indicated that LEFTY2 is a good AH biomarker for XFG (CAT vs. XFG, AUC = 0.87; P < 0.0001). LEFTY2 AH levels were highest in eyes judged to have the heaviest XFM deposits (ρ = 0.341, P = 0.0054). Plasma LEFTY2 levels did not correlate with disease status or ocular LEFTY2 levels. TGFβ treatment significantly increased LEFTY2 expression in HTM cells.
CONCLUSIONS: LEFTY2 is a promising AH biomarker for XFG. Its clinical value may be limited by accessibility, OD/OS discordance, and interpatient variability. Its role in XFG pathogenesis requires further study.
TRANSLATIONAL RELEVANCE: Identification of biomarkers for XFG may improve early detection and treatment.