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Abstract #92680 Published in IGR 22-1
Anti-fibrotic activity of a rho-kinase inhibitor restores outflow function and intraocular pressure homeostasis
Li G; Lee C; Read AT; Wang K; Ha J; Kuhn M; Navarro I; Cui J; Young K; Gorijavolu R; Sulchek T; Kopczynski C; Farsiu S; Samples J; Challa P; Ethier CR; Stamer WDeLife 2021; 10:
Glucocorticoids are widely used as an ophthalmic medication. A common, sight-threatening adverse event of glucocorticoid usage is ocular hypertension, caused by dysfunction of the conventional outflow pathway. We report that netarsudil, a rho-kinase inhibitor, decreased glucocorticoid-induced ocular hypertension in patients whose intraocular pressures were poorly controlled by standard medications. Mechanistic studies in our established mouse model of glucocorticoid-induced ocular hypertension show that netarsudil both prevented and reduced intraocular pressure elevation. Further, netarsudil attenuated characteristic steroid-induced pathologies as assessed by quantification of outflow function and tissue stiffness, and morphological and immunohistochemical indicators of tissue fibrosis. Thus, rho-kinase inhibitors act directly on conventional outflow cells to prevent or attenuate fibrotic disease processes in glucocorticoid-induced ocular hypertension in an immune-privileged environment. Moreover, these data motivate the need for a randomized prospective clinical study to determine whether netarsudil is indeed superior to first-line anti-glaucoma drugs in lowering steroid-induced ocular hypertension.
Department of Ophthalmology, Duke University, Durham, United States.
Full articleClassification:
12.8.10 Woundhealing antifibrosis (Part of: 12 Surgical treatment > 12.8 Filtering surgery)
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
2.6.2.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.6 Aqueous humor dynamics > 2.6.2 Outflow)
3.9 Pathophysiology (Part of: 3 Laboratory methods)