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In vitro and in vivo evaluation of a preservative-free cationic emulsion of latanoprost in corneal wound healing models.
- Source :
-
Cornea [Cornea] 2012 Nov; Vol. 31 (11), pp. 1319-29. - Publication Year :
- 2012
-
Abstract
- Purpose: Cationic emulsions (CEs), developed as vehicles for lipophilic drugs, have been shown to be safe and effective for the treatment of dry eye. The aim of this study was to investigate the effects of a preservative-free latanoprost 0.005% CE (latanoprost-CE) in in vitro and in vivo models of corneal wound healing.<br />Methods: An in vitro wound was made by scraping through a confluent layer of human corneal epithelial cells. Cytotoxicity, cell migration, and proliferation were analyzed after an exposure to phosphate-buffered saline, CE, latanoprost-CE, 0.02% benzalkonium chloride (0.02%BAK), and Xalatan (latanoprost). In vivo, the recovery and integrity of corneal wound healing were assessed in rat eyes instilled twice a day for 5 days with the above treatments after deepithelialization of the superior cornea.<br />Results: In vitro wound distances decreased at 2 and 24 hours for human corneal epithelial cells exposed to CE, latanoprost-CE, and phosphate-buffered saline, whereas they progressively increased for 0.02%BAK-treated and latanoprost-treated cells. The greater wound closure was associated with a higher number of Ki67-positive cells. In CE- and latanoprost-CE-treated rats, reepithelialization of the cornea was enhanced, restoring normal appearance and function. In contrast, 0.02%BAK or latanoprost delayed corneal healing, induced inflammation, and decreased MUC5-AC expression.<br />Conclusions: Both models effectively evaluated the cytotoxicity and dynamic recovery of corneal wound healing, and their correlation supports the potential of the in vitro model as a reliable alternative to in vivo ocular toxicity tests. Both models demonstrated that in the face of corneal injury, CEs favored corneal healing, whereas BAK was deleterious.
- Subjects :
- Animals
Benzalkonium Compounds toxicity
Cell Proliferation drug effects
Cells, Cultured
Conjunctiva drug effects
Conjunctiva metabolism
Cornea drug effects
Cornea metabolism
Drug Evaluation, Preclinical
Emulsions
Epithelium, Corneal drug effects
Epithelium, Corneal metabolism
Eye Injuries metabolism
Eye Injuries pathology
Humans
Ki-67 Antigen metabolism
Latanoprost
Male
Microscopy, Confocal
Mucin 5AC metabolism
Rats
Antihypertensive Agents toxicity
Corneal Injuries
Disease Models, Animal
Eye Injuries drug therapy
Preservatives, Pharmaceutical toxicity
Prostaglandins F, Synthetic toxicity
Wound Healing drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1536-4798
- Volume :
- 31
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Cornea
- Publication Type :
- Academic Journal
- Accession number :
- 22929154
- Full Text :
- https://doi.org/10.1097/ICO.0b013e318255a7f8