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Abstract #90684 Published in IGR 21-3

Ripasudil in a Model of Pigmentary Glaucoma

Wang C; Dang Y; Waxman S; Hong Y; Shah P; Loewen RT; Xia X; Loewen NA
Translational vision science & technology 2020; 9: 27

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PURPOSE: To investigate the effects of Ripasudil (K-115), a Rho-kinase inhibitor, in a porcine model of pigmentary glaucoma. METHODS: In vitro trabecular meshwork (TM) cells and ex vivo perfused eyes were subjected to pigment dispersion followed by K-115 treatment (PK115). PK115 was compared to controls (C) and pigment (P). Cytoskeletal alterations were assessed by F-actin labeling. TM cell phagocytosis of fluorescent targets was evaluated by flow cytometry. Cell migration was studied with a wound-healing assay. Intraocular pressure was continuously monitored and compared to after the establishment of the pigmentary glaucoma model and after treatment with K-115. RESULTS: The percentage of cells with stress fibers increased in response to pigment but declined sharply after treatment with K-115 (P: 32.8% ± 2.9%; PK115: 11.6% ± 3.3%, < 0.001). Phagocytosis first declined but recovered after K-115 (P: 25.7% ± 2.1%, PK115: 33.4% ± 0.8%, <0.01). Migration recuperated at 12 hours with K-115 treatment (P: 19.1 ± 4.6 cells/high-power field, PK115: 42.5 ± 1.6 cells/high-power field, < 0.001). Ex vivo, eyes became hypertensive from pigment dispersion but were normotensive after treatment with K-115 (P: 20.3 ± 1.2 mm Hg, PK115: 8.9 ± 1.7 mm Hg; < 0.005). CONCLUSIONS: In vitro, K-115 reduced TM stress fibers, restored phagocytosis, and restored migration of TM cells. Ex vivo, K-115 normalized intraocular pressure. TRANSLATIONAL RELEVANCE: This ex vivo pigmentary glaucoma model provides a readily available basis to investigate new drugs such as the rho-kinase inhibitor studied here.

Full article

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Classification:

9.4.3.1 Pigmentary glaucoma (Part of: 9 Clinical forms of glaucomas > 9.4 Glaucomas associated with other ocular and systemic disorders > 9.4.3 Glaucomas associated with disorders of the iris and ciliary body)
3.6 Cellular biology (Part of: 3 Laboratory methods)
5.3 Other (Part of: 5 Experimental glaucoma; animal models)
11.15 Other drugs in relation to glaucoma (Part of: 11 Medical treatment)

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