Though the most common use of rho-kinase (ROCK) inhibitors in eye care is for IOP lowering in glaucoma, the drug class has been steadily racking up evidence for an beneficial effect on endothelial cell integrity.
These agents have been successful in saving eyes that failed to clear following descemetorhexis without endothelial grafting for Fuchs’ dystrophy, and a recent study tested the ROCK inhibitor ripasudil in ex vivo and in vitro models, finding it effective in the presence of pathological guttae and able to upregulate key proteins.
The researchers used endothelial cell–Descemet membrane lamellae from 450 Fuchs’ patients undergoing DMEK for their ex vivo model. Other models included normal, research-grade donor corneas (n=30) harvested from central endothelial cells (ex vivo), normal donor corneas (n=20) without endothelial injury and immortalized cell lines (n=3) generated from Fuchs’ patients (in vitro).
The lamellae were incubated for one to three days with or without a 30μM dose of ripasudil. The researchers reported that a single dose of ripasudil induced significant upregulation of several genes and proteins, including:
- Genes and proteins related to cell cycle progression
- Cell-matrix adhesion and migration
- Endothelial barrier function
- Pump function
They noted that ripasudil downregulated markers of endothelial-to-mesenchymal transition in both Fuchs’ and normal corneas compared with unstimulated controls ex vivo. Additionally, they observed ripasudil-induced changes in expression of function signature genes in Fuchs’ cell lines in vitro.
The researchers concluded that their data support the use of ROCK inhibitors as a “potent tool” in regenerative Fuchs’ therapies. Ripasudil did not induce adverse phenotypic changes.
Schlötzer-Schrehardt U, Zenkel M, Strunz M, et al. Potential function restoration of corneal endothelial cells in Fuchs endothelial corneal dystrophy by ROCK inhibitor (ripasudil). Am J Ophthalmol. December 10, 2020. [Epub ahead of print].