The ocular surface · 2025
Prostaglandin F2α exacerbated dry eye by promoting lacrimal gland fibrosis progression through the activation of the RhoA/ROCKs signaling pathway.
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Guo Shujia, Kang Jiayu, Yan Ke, Li Jiani, Wang Ruochen, Qin Danyi, Wang Yuqian, Liu Yuwen, Guan Wenying, Wu Han, Hu Jiaoyue, Li Wei, Chen Yongxiong, Huang Caihong, Liu Zuguo
Аннотация
PURPOSE: To investigate Prostaglandin F2α (PGF2α) expression in dry eye (DE) patients and its correlation with clinical manifestations, exploring potential mechanisms in DE.
METHODS: Cross-sectional case-control study including 21 DE patients and 16 controls. PGF2α levels were detected by ELISA (Enzyme-linked immunosorbent assay). Correlation analyses were conducted between PGF2α in human tears and DE symptoms (The Ocular Surface Disease Index, OSDI) or signs including tear film breakup time using fluorescein sodium strips (FBUT), Schirmer Ⅰ test (ST) and corneal fluorescein staining (CFS). Dry eye models were induced using scopolamine and desiccating stress, with transcriptomic sequencing to analyze differential gene expression. DE mice were treated with the PGF2α receptor inhibitor AL8810. Various assays (Oregon green dextran staining, phenol red thread test, PCR, immunofluorescence, MASSON staining, ELISA, Western Blot) evaluated DE phenotypes, lacrimal gland inflammation, and fibrosis.
RESULTS: DE patients had significantly elevated PGF2α levels, negatively correlating with ST and positively with CFS. DE mice showed increased PGF2α and FP receptor expression in lacrimal glands, decreased tear production, worsening ocular surface damage, and elevated inflammation and fibrosis. The TGFβ1/Smads and RhoA/ROCKs pathways were activated, with changes becoming more pronounced with extended molding time. AL8810 reduced fibrosis, partially restored tear secretion, and alleviated corneal damage while inhibiting RhoA/ROCKs pathway activation without affecting TGFβ1 expression.
CONCLUSIONS: PGF2α exacerbated DE by promoting lacrimal gland fibrosis progression via the RhoA/ROCKs signaling pathway. Inhibiting PGF2α receptors effectively suppressed the progression of dry eye and lacrimal gland fibrosis, which may offer a promising therapeutic strategy for DE, particularly in refractory cases associated with lacrimal gland fibrosis.
METHODS: Cross-sectional case-control study including 21 DE patients and 16 controls. PGF2α levels were detected by ELISA (Enzyme-linked immunosorbent assay). Correlation analyses were conducted between PGF2α in human tears and DE symptoms (The Ocular Surface Disease Index, OSDI) or signs including tear film breakup time using fluorescein sodium strips (FBUT), Schirmer Ⅰ test (ST) and corneal fluorescein staining (CFS). Dry eye models were induced using scopolamine and desiccating stress, with transcriptomic sequencing to analyze differential gene expression. DE mice were treated with the PGF2α receptor inhibitor AL8810. Various assays (Oregon green dextran staining, phenol red thread test, PCR, immunofluorescence, MASSON staining, ELISA, Western Blot) evaluated DE phenotypes, lacrimal gland inflammation, and fibrosis.
RESULTS: DE patients had significantly elevated PGF2α levels, negatively correlating with ST and positively with CFS. DE mice showed increased PGF2α and FP receptor expression in lacrimal glands, decreased tear production, worsening ocular surface damage, and elevated inflammation and fibrosis. The TGFβ1/Smads and RhoA/ROCKs pathways were activated, with changes becoming more pronounced with extended molding time. AL8810 reduced fibrosis, partially restored tear secretion, and alleviated corneal damage while inhibiting RhoA/ROCKs pathway activation without affecting TGFβ1 expression.
CONCLUSIONS: PGF2α exacerbated DE by promoting lacrimal gland fibrosis progression via the RhoA/ROCKs signaling pathway. Inhibiting PGF2α receptors effectively suppressed the progression of dry eye and lacrimal gland fibrosis, which may offer a promising therapeutic strategy for DE, particularly in refractory cases associated with lacrimal gland fibrosis.
Предметные рубрики MeSH
Dry Eye SyndromesHumansAnimalsDinoprostMiceLacrimal ApparatusrhoA GTP-Binding ProteinMaleTearsSignal TransductionFemaleFibrosisrho-Associated KinasesMiddle AgedCross-Sectional StudiesDisease Models, AnimalCase-Control StudiesDisease ProgressionEnzyme-Linked Immunosorbent AssayAdultBlotting, WesternMice, Inbred C57BL