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Published on: January 10, 2025
Effects of antiglaucoma drugs on cellular proliferation in cultured human corneal keratocytes
Kwou-Yeung Wu1, Hwei-Zu Wang, Show-Jen Hong
1Department of Ophthalmology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan.
Abstract:
The purpose of this study was to investigate the effects of various antiglaucoma drugs, including timolol, betaxolol, carteolol, levobunolol, dipivefrin, and pilocarpine, on cellular proliferation in cultured human corneal keratocytes. Human corneal keratocytes were cultured with RPMI-1640 medium containing 10% fetal bovine serum. Antiglaucoma drugs were prepared from original concentrations to dilutions of 1/10, 1/100, and 1/1,000. After exposure to drugs for 100 minutes, cellular proliferation was estimated by [3H]thymidine uptake methodology. It was found that cellular proliferation in corneal keratocytes was inhibited by only a 1/10 dilution of various drugs including timolol, betaxolol, carteolol, levobunolol, dipivefrin, and pilocarpine. The [3H]thymidine uptake values were significantly inhibited to 63%, 18%, 87%, 68%, 55%, and 67% by a 1/10 dilution of the above drugs. However, the cellular proliferation was also significantly suppressed by 0.01 mg/mL of benzalkonium chloride preservative. It is shown that the inhibition of cellular proliferation by high concentrations of antiglaucoma drugs may result from the benzalkonium chloride preservative contained in these drugs.
Insights
Antiglaucoma drugs, at high concentrations, inhibited corneal keratocyte proliferation, likely due to the benzalkonium chloride preservative. Further research is needed to understand the specific mechanisms.
Area of Science:
- Ophthalmology
- Cell Biology
- Pharmacology
Background:
- Glaucoma is a leading cause of irreversible blindness.
- Antiglaucoma medications are crucial for managing intraocular pressure.
- Corneal health is vital for ocular function and drug delivery.
Purpose of the Study:
- To evaluate the impact of common antiglaucoma drugs on human corneal keratocyte proliferation.
- To determine if antiglaucoma drugs directly affect corneal cell growth or if preservatives are responsible.
Main Methods:
- Cultured human corneal keratocytes were exposed to various antiglaucoma drugs (timolol, betaxolol, carteolol, levobunolol, dipivefrin, pilocarpine) at different dilutions.
- Cellular proliferation was quantified using the [3H]thymidine uptake assay.
- The effect of benzalkonium chloride preservative alone was also assessed.
Main Results:
- A 1/10 dilution of all tested antiglaucoma drugs significantly inhibited keratocyte proliferation.
- Specific inhibition percentages ranged from 18% to 87% depending on the drug.
- Benzalkonium chloride preservative at 0.01 mg/mL also significantly suppressed cellular proliferation.
Conclusions:
- High concentrations of antiglaucoma drugs inhibit corneal keratocyte proliferation.
- The observed inhibition is likely attributable to the benzalkonium chloride preservative present in the formulations.
- This finding has implications for understanding potential side effects of topical ocular medications on corneal health.
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