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Jia Yin, Fushin X Yu, Mark McDermott; Effects of Prostaglandin Analogues on Corneal Epithelial and Keratocyte Viability and Wound Healing. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1496.
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Toxicity of glaucoma medications including prostaglandin analogues (PGAs) on ocular surface is not uncommon and both preservatives including benzalkonium (BAK) and active ingredients have been implicated. Current project was designed to compare the effects of PGAs on the viability and wound healing of corneal epithelial cells and keratocytes. Tested commercial formulations included 0.005% latanoprost (Xalatan, 0.02% BAK), 0.004% travoprost (Travatan Z, preserved in sofZia®, an ionic buffered system), 0.01% bimatoprost (Lumigan 0.01%, 0.02% BAK), and 0.0015% tafluprost (Zioptan, no preservative).
Cultured human corneal epithelial cells and keratocytes (stromal fibroblasts) were exposed to PGAs for 10 minutes and cell viability/cytotoxicity was determined by colorimetric MTT assay (n=4). Culture medium was used as a negative control and viability reduction was calculated as a percentage decrease compared to negative control. Triton X-100 detergent 1% (TX100) was used as a positive control. A 5 mm central epithelial lesion was made in porcine corneas (n = 3). After 24 hours, corneas were incubated with culture medium containing study medications for 10 minutes. After rinsing, corneas were cultured for an additional 24 hours. The remaining wound area was stained with Richardson’s staining solution, photographed, and quantified using Adobe Photoshop. Student t-test was performed using Sigma-Stat.
In corneal epithelial cells, cell viability was reduced by travoprost (25%), bimatoprost (81%), latanoprost (93%), and TX100 (94%), P<0.001 compared to negative control and between test medications. In keratocytes, cell viability was unaffected by travoprost (P=0.592), slightly reduced by tafluprost (20% but P=0.264), and significantly decreased by latanoprost (80%) and TX100 (81%), P<0.001. While remaining epithelial wound areas in porcine corneas exposed to bimatoprost and travoprost were similar to negative controls cultured in medium (P=0.829 and P=0.141 respectively), those exposed to latanoprost and TX100 were significantly decreased by 17% and 94% respectively (P<0.001).
Both preservative BAK and active ingredients in PGAs affect cell viability and wound healing of corneal epithelial cells and keratocytes. Among the medications tested, travoprost preserved in sofZia® has least adverse effects, and latanoprost had the most.
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