Abstract
Purpose :
This study aims to investigate the potential of beta blockers in reducing corneal neovascularization.
Methods :
The cytotoxicity of propranolol, metoprolol, and timolol were assessed using MTS on various endothelial cells, including EOMA, HUVEC, and CPAE.
Tunnel assay and sub-G1 assay via flow cytometry were employed to investigate cell death through apoptosis. Cleaved caspases 7 and PARP were analyzed in beta blockers-treated cells to understand the mechanism of apoptosis.
The effect of beta-blockers on eliminating pre-matured blood vessels in the injured cornea was investigated by topical application ten days after alkali burn.
Histochemistry analysis was used to assess differences in corneal structure and infiltrated immune cells among wild-type, DMSO, and beta blockers-treated corneas.
Results :
The tested three beta-blockers exhibited cytotoxicity with an IC50 of 200 μM on various endothelial cells. However, 80% of corneal fibroblasts and epithelial cells survived at 200 μM of beta blockers. Propranolol and metoprolol induced endothelial cell apoptosis through the activation of caspases 7 and PARP as a mechanism of action. After two weeks of treatment, propranolol and timolol halted the growth of pathological blood vessels and eliminated existing blood vessels in alkali burn-induced blood vessels. However, continued blood vessel growth was observed in DMSO and metoprolol-treat cornea. Corneal structure on propranolol and timolol-treated eye exhibited significant recovery from alkali burn, with a thickened epithelium layer and restored stroma layer compared to DMSO and metoprolol-treated cornea. Additionally, a lower number of infiltrated immune cells were identified in propranolol and timolol-treated cornea.
Conclusions :
In this study, we conducted a comparative analysis of three beta-blockers based on their selectivity: propranolol and timolol as non-selective beta-blockers, and metoprolol as a selective beta-blocker, aiming to assess their effectiveness in reducing neovascularization in the injured cornea. Our results indicate that non-selective beta-blockers, propranolol, and timolol demonstrated superior performance in reducing pathological blood vessels compared to the selective beta-blocker metoprolol. This led to significant inhibition of inflammation, suggesting the potential of non-selective beta-blockers in effectively addressing neovascularization-associated issues in the injured cornea.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.