4.7 Article

Cytotoxicity, Mitochondrial Functionality, and Redox Status of Human Conjunctival Cells after Short and Chronic Exposure to Preservative-Free Bimatoprost 0.03% and 0.01%: An In Vitro Comparative Study

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MDPI
DOI: 10.3390/ijms232214113

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bimatoprost; preservative-free; glaucoma; human conjunctival epithelial cells; cell cycle; mitochondrial activity; ROS; apoptosis

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This study evaluated the in vitro effects of preservative-free bimatoprost (BIM) 0.03% vs. 0.01% on human conjunctival epithelial (HCE) cells. The results showed that long-term exposure to BIM 0.03% resulted in a significant decrease in cell proliferation and viability, as well as alterations in cell cycle and mitochondrial function. BIM 0.01% did not exhibit cytotoxicity or negative influence on conjunctival cell growth and viability.
Prostaglandin analogues (PGAs), including bimatoprost (BIM), are generally the first-line therapy for glaucoma due to their greater efficacy, safety, and convenience of use. Commercial solutions of preservative-free BIM (BIM 0.03% and 0.01%) are already available, although their topical application may result in ocular discomfort. This study aimed to evaluate the in vitro effects of preservative-free BIM 0.03% vs. 0.01% in the human conjunctival epithelial (HCE) cell line. Our results showed that long-term exposure to BIM 0.03% ensues a significant decrease in cell proliferation and viability. Furthermore, these events were associated with cell cycle arrest, apoptosis, and alterations of Delta psi(m). BIM 0.01% does not exhibit cytotoxicity, and no negative influence on conjunctival cell growth and viability or mitochondrial activity has been observed. Short-time exposure also demonstrates the ability of BIM 0.03% to trigger reactive oxygen species (ROS) production and mitochondrial hyperpolarisation. An in silico drug network interaction was also performed to explore known and predicted interactions of BIM with proteins potentially involved in mitochondrial membrane potential dissipation. Our findings overall strongly reveal better cellular tolerability of BIM 0.01% vs. BIM 0.03% in HCE cells.

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