Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2026
Pirfenidone Inhibits Inflammatory Mediators in Human Cornea In Vitro.
СтатьяНазвание и аннотация: Перевод в очереди
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Hofmann Alexandria C, Sinha Nishant R, Hurtado Abigail, Davis Alaina R, Suleiman Laila A, Kamryn Bene, Kumar Rajnish, Mohan Rajiv R
Аннотация
PURPOSE: Corneal inflammation is a common clinical condition that contributes to loss of corneal transparency. This study evaluated the potential of pirfenidone (PFD), an FDA-approved drug, to inhibit inflammation in the human cornea using an in vitro model.
METHODS: Healthy cadaver human corneas and standard in vitro corneal inflammation models were used. Primary human corneal stromal fibroblasts (hCSFs) generated from donor corneas were used in the entire study. The dose-dependent assays identified optimal lipopolysaccharide (LPS; 0-150 ng/ml) concentration to induce inflammation and PFD's (0-500 µg/mL) half-maximal inhibitory concentration (IC50) to hCSF. The quantitative reverse transcriptase polymerase chain reaction, immunofluorescence, Western blotting, and reactive oxygen species (ROS) commercial kits studied changes in inflammatory response.
RESULTS: A significant upregulation of inflammatory markers in hCSF at 48 h was noted at 50 ng/ml of LPS concentration. The IC50 of PFD was found to be 200 µg/mL for hCSFs. Topical treatments of PFD (200 µg/mL) significantly reduced LPS (50 µg/mL)-induced levels of pro-inflammatory (TNFα, IL1α, IL1β, IL6, and cyclooxygenase 2) markers and oxidative stress (glutathione peroxidase 1 [GPX1], GPX4, and catalase) genes (P < 0.001 or P < 0.0001) in human corneas in vitro. Moreover, PFD significantly inhibited LPS-increased ROS production (P < 0.001) in hCSF. PFD treatment reduced LPS-induced inflammatory stimulation and tumor necrosis factor alpha and IκB alpha phosphorylation in hCSF.
CONCLUSION: PFD inhibits corneal inflammation in vitro by reducing pro-inflammatory cytokines and oxidative stress. Comprehensive preclinical animal testing is warranted to define the potential of PFD to treat corneal symptoms in vivo in traumatic eyes.
METHODS: Healthy cadaver human corneas and standard in vitro corneal inflammation models were used. Primary human corneal stromal fibroblasts (hCSFs) generated from donor corneas were used in the entire study. The dose-dependent assays identified optimal lipopolysaccharide (LPS; 0-150 ng/ml) concentration to induce inflammation and PFD's (0-500 µg/mL) half-maximal inhibitory concentration (IC50) to hCSF. The quantitative reverse transcriptase polymerase chain reaction, immunofluorescence, Western blotting, and reactive oxygen species (ROS) commercial kits studied changes in inflammatory response.
RESULTS: A significant upregulation of inflammatory markers in hCSF at 48 h was noted at 50 ng/ml of LPS concentration. The IC50 of PFD was found to be 200 µg/mL for hCSFs. Topical treatments of PFD (200 µg/mL) significantly reduced LPS (50 µg/mL)-induced levels of pro-inflammatory (TNFα, IL1α, IL1β, IL6, and cyclooxygenase 2) markers and oxidative stress (glutathione peroxidase 1 [GPX1], GPX4, and catalase) genes (P < 0.001 or P < 0.0001) in human corneas in vitro. Moreover, PFD significantly inhibited LPS-increased ROS production (P < 0.001) in hCSF. PFD treatment reduced LPS-induced inflammatory stimulation and tumor necrosis factor alpha and IκB alpha phosphorylation in hCSF.
CONCLUSION: PFD inhibits corneal inflammation in vitro by reducing pro-inflammatory cytokines and oxidative stress. Comprehensive preclinical animal testing is warranted to define the potential of PFD to treat corneal symptoms in vivo in traumatic eyes.