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Induction of Ocular Surface Inflammation and Collection of Involved Tissues
Published on: August 4, 2022
Effects of Four Formulations of Prostaglandin Analogs on Eye Surface Cells. A Comparative Study
Fernando Pérez-Roca1, Esther Rodrigo-Morales2, Ingrid Garzón3
1Hospital General Básico de Baza, E18800, Granada, Spain; PhD Program in Biomedicine, University of Granada, 18012, Granada, Spain.
Abstract:
We evaluated the cytotoxic effects of four prostaglandin analogs (PGAs) used to treat glaucoma. First we established primary cultures of conjunctival stromal cells from healthy donors. Then cell cultures were incubated with different concentrations (0, 0.1, 1, 5, 25, 50 and 100%) of commercial formulations of bimatoprost, tafluprost, travoprost and latanoprost for increasing periods (5 and 30 min, 1 h, 6 h and 24 h) and cell survival was assessed with three different methods: WST-1, MTT and calcein/AM-ethidium homodimer-1 assays. Our results showed that all PGAs were associated with a certain level of cell damage, which correlated significantly with the concentration of PGA used, and to a lesser extent with culture time. Tafluprost tended to be less toxic than bimatoprost, travoprost and latanoprost after all culture periods. The results for WST-1, MTT and calcein/AM-ethidium homodimer-1 correlated closely. When the average lethal dose 50 was calculated, we found that the most cytotoxic drug was latanoprost, whereas tafluprost was the most sparing of the ocular surface in vitro. These results indicate the need to design novel PGAs with high effectiveness but free from the cytotoxic effects that we found, or at least to obtain drugs that are functional at low dosages. The fact that the commercial formulation of tafluprost used in this work was preservative-free may support the current tendency to eliminate preservatives from eye drops for clinical use.
Insights
This study assessed the cytotoxicity of four prostaglandin analogs (PGAs) used for glaucoma treatment. Tafluprost demonstrated the least ocular surface toxicity in vitro, suggesting a need for less cytotoxic glaucoma medications.
Area of Science:
- Ophthalmology
- Cell Biology
- Pharmacology
Background:
- Glaucoma treatment often involves prostaglandin analogs (PGAs).
- Understanding the in vitro cytotoxicity of PGAs is crucial for ocular surface health.
- Previous studies have indicated potential cellular damage from PGA use.
Purpose of the Study:
- To evaluate and compare the cytotoxic effects of four common prostaglandin analogs (bimatoprost, tafluprost, travoprost, latanoprost) on human conjunctival stromal cells.
- To determine the concentration- and time-dependent cytotoxicity of these PGAs.
- To identify PGAs with a more favorable safety profile for ocular surface tissues.
Main Methods:
- Primary cultures of human conjunctival stromal cells were established.
- Cells were exposed to varying concentrations and durations of four commercial PGAs: bimatoprost, tafluprost, travoprost, and latanoprost.
- Cell viability was assessed using WST-1, MTT, and calcein/AM-ethidium homodimer-1 assays.
Main Results:
- All tested PGAs exhibited dose-dependent cytotoxicity, with increased damage at higher concentrations and longer exposure times.
- Tafluprost showed a trend towards lower toxicity compared to bimatoprost, travoprost, and latanoprost across all tested periods.
- Latanoprost was identified as the most cytotoxic PGA, while tafluprost was the least cytotoxic, preserving ocular surface cells in vitro.
Conclusions:
- Novel prostaglandin analogs should be developed with reduced cytotoxic potential while maintaining efficacy for glaucoma management.
- Tafluprost appears to be a safer option for the ocular surface compared to other PGAs studied.
- The preservative-free formulation of tafluprost used may align with the clinical trend of preservative elimination in eye drops.
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