Ripasudil in a Model of Pigmentary Glaucoma.

Abstract

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%, P < 0.001). Phagocytosis first declined but recovered after K-115 (P: 25.7% ± 2.1%, PK115: 33.4% ± 0.8%, P <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, P < 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; P < 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.

• Authors: Chao Wang, Yalong Dang, Susannah Waxman, Ying Hong, Priyal Shah, Ralitsa T Loewen, Xiaobo Xia, Nils A Loewen
• Journal: Translational vision science & technology (Transl Vis Sci Technol) Vol. 9 Issue 10 Pg. 27 (09 2020) ISSN: 2164-2591 [Print] United States
• PMID: 33024620 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2020 The Authors.

Chemical References

• Isoquinolines
• K-115
• Sulfonamides

Topics

• Animals
• Glaucoma, Open-Angle (drug therapy)
• Intraocular Pressure
• Isoquinolines
• Stress Fibers
• Sulfonamides
• Swine
• Trabecular Meshwork