Corneal Protection by the Ocular Mucin Secretagogue 15(S)-HETE in a Rabbit Model of Desiccation-induced Corneal Defect
| Autor: | Joan M. Spellman, Lori K. Weimer, Zhongyou Wei, Steven T. Miller, Daniel A. Gamache, John M. Yanni |
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| Rok vydání: | 2002 |
| Předmět: |
medicine.medical_specialty
genetic structures Administration Topical medicine.medical_treatment In Vitro Techniques Tachyphylaxis Biology Ophthalmology Hydroxyeicosatetraenoic Acids medicine Animals Humans Pharmacology (medical) Desiccation ED50 Pharmacology Dose-Response Relationship Drug Mucin Epithelium Corneal Mucins Anatomy eye diseases Artificial tears Corneal defect Rabbit model lipids (amino acids peptides and proteins) Secretagogue Rabbits sense organs |
| Zdroj: | Journal of Ocular Pharmacology and Therapeutics. 18:349-361 |
| ISSN: | 1557-7732 1080-7683 |
| DOI: | 10.1089/10807680260218515 |
| Popis: | The mucin secretagogue 15(S)-HETE was found to stimulate glycoprotein secretion in human ocular tissue at submicromolar concentrations in the present studies. Therefore, the ability of topically applied 15(S)-HETE to preserve corneal integrity was investigated in a rabbit model of desiccation-induced corneal defect. Desiccation-induced corneal injury was elicited in anesthetized rabbits by maintaining one eye open with a speculum. Corneal staining and corneal thickness changes were determined immediately following desiccation. 15(S)-HETE dose-dependently reduced corneal damage (ED50 = 120 nM) during a two-hour desiccation. Corneal staining was unchanged relative to control using a 1 microM dose of 15(S)-HETE. Through four hours of desiccation, 15(S)-HETE (500 nM) decreased corneal staining by 71% and completely prevented corneal thinning. 15(S)-HETE (1 microM) was significantly more efficacious than an artificial tear product over the 4-hour desiccation period. There was no evidence of tachyphylaxis following repeated topical ocular dosing of 15(S)-HETE. These studies demonstrate that 15(S)-HETE stimulates ocular mucin secretion in vitro and effectively protects the cornea in a rabbit model of desiccation-induced injury. The results suggest that the ocular mucin secretagogue 15(S)-HETE may have therapeutic utility in dry eye patients, alleviating corneal injury and restoring corneal integrity. |
| Databáze: | OpenAIRE |
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