Current Eye Research, Год журнала: 2025, Номер unknown, С. 1 - 11
Опубликована: Июнь 2, 2025
To quantitatively evaluate the IOP-lowering efficacy of topical KD025 in normotensive and steroid-induced ocular hypertensive rat models, to elucidate its mechanisms concerning TM cytoskeletal remodeling, fibrotic modulation, cell behavior using primary human cells. Normotensive (dexamethasone) Sprague-Dawley rats received KD025; IOP was monitored rebound tonometry. morphology assessed by H&E staining. In cells, functional effects (wound healing) expression α-smooth muscle actin (α-SMA), fibronectin (FN), F-actin, myocilin (a steroid-response marker) were analyzed via immunofluorescence Western blotting following and/or dexamethasone treatment. significantly reduced rats, with peak at 6 h post-administration (though no clear dose-dependency observed between 10-25 µM). 20 µM achieved greater reduction versus vehicle (p < 0.01). Histological analysis suggested potential structural relaxation. vitro, inhibited migration downregulated dexamethasone-induced α-SMA expression. Paradoxically, differing from typical pan-ROCK inhibitor effects, treatment increased total cellular FN protein 0.01 vs DEX alone) further exacerbated F-actin levels 0.05 alone). demonstrates effective capabilities rodent models. Its mechanism likely involves modulating contractility (via reduction) inhibiting migration. The unexpected findings on suggest that selective ROCK2 inhibition induces complex distinct extracellular matrix dynamics organization compared non-selective ROCK inhibitors. These results highlight as a promising therapeutic target for glaucoma, though actions warrant investigation.
Язык: Английский