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Timolol Inhibits Corneal Epithelial Wound Healing in Rabbits and Monkeys

Timolol Inhibits Corneal Epithelial Wound Healing in Rabbits and Monkeys Abstract • To determine the effect of timolol maleate on corneal epithelial wound closure, 6.4-mm (diameter) epithelial defects were created chemically in five experiments. In rabbits, wound closure was not significantly altered by the administration of 0.5% Timoptic (a commercially prepared timolol maleate solution) every eight hours, but it was inhibited during the first 15 hours of healing when a 4% solution was applied every two hours. Monkeys received a 5% solution every 12 hours and were divided into treated and control groups. Two phases of wound healing were apparent: a rapid initial phase and a slower final phase. Wound closure was inhibited in treated eyes during the initial rapid phase. This experiment repeated on the same monkeys, but with the control and treated animals switched, yielded the same result. Another experiment, with the fellow eye of the monkey used as a control, showed no significant difference in wound closure. References 1. Van Buskirk EM: Corneal anesthesia after timolol maleate therapy . Am J Ophthalmol 1979; 88:739-743. 2. Nielsen NV, Eriksen JS: Timolol: Transitory manifestations of dry eyes in long term treatment . Acta Ophthalmol 1979;57:418-424.Crossref 3. Butterfield LC, Neufeld AH: Cyclic nucleotides and mitosis in the rabbit cornea following superior cervical ganglionectomy . Exp Eye Res 1977;25:427-433.Crossref 4. Klyce SD, Neufeld AH, Zadunaisky JA: The activation of chloride transport by epinephrine and Db cyclic-AMP in the cornea of the rabbit . Invest Ophthalmol Vis Sci 1973;12:127-139. 5. Fisher F, Wiederholt M: Sodium and chloride transport in the isolated human cornea . Invest Ophthalmol Vis Sci 1975;14( (ARVO suppl) ):26. 6. Fogle JA, Neufeld AH: The adrenergic and cholinergic corneal epithelium . Invest Ophthalmol Vis Sci 1979;18:1212-1215. 7. Berridge MJ: The interaction of cyclic nucleotides and calcium in the control of cellular activity . Adv Cyclic Nucleotide Res 1975;6:1-98. 8. Jumblatt MM, Fogle JA, Neufeld AH: Cholera toxin stimulates adenosine 3',5'-monophosphate synthesis and epithelial wound closure in the rabbit cornea . Invest Ophthalmol Vis Sci 1980;19:1321-1327. 9. Jumblatt MM, Neufeld AH: Characterization of cyclic AMP-mediated wound closure of the rabbit corneal epithelium . Curr Eye Res 1981;1:189-195.Crossref 10. O'Brien WJ, DeCarlo JD, Stern M, et al: Effects of Timoptic on corneal reepithelialization . Arch Ophthalmol 1982;100:1331-1333.Crossref 11. Bartels SP, Roth HO, Jumblatt MM, et al: Pharmacological effects of timolol in the rabbit eye . Invest Ophthalmol Vis Sci 1980;19:1190-1197. 12. Zimmerman TJ, Kaufman HE: Timolol: A β-adrenergic agent for the treatment of glaucoma . Arch Ophthalmol 1977;95:601-604.Crossref 13. Cintron C, Hassinger L, Kublin CL, et al: A simple method for the removal of rabbit and corneal epithelium utilizing n-heptanol . Ophthalmic Res 1979;11:90-96.Crossref 14. Ubels JL, Edelhauser HF, Austin KH: A comparison of healing of corneal epithelial wounds stained with fluorescein or Richardson's stain . Invest Ophthalmol Vis Sci 1982;23:127-31. 15. Vareilles P, Silverstone D, Plazonnet B, et al: Comparison of the effects of timolol and other adrenergic agents on intraocular pressure in the rabbit . Invest Ophthalmol Vis Sci 1977;16:987-996. 16. Katz IM, Hubbard WA, Getson AJ, et al: Intraocular pressure decrease in normal volunteers following timolol ophthalmic solution . Invest Ophthalmol Vis Sci 1976;15:489-492. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Ophthalmology American Medical Association

Timolol Inhibits Corneal Epithelial Wound Healing in Rabbits and Monkeys

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References (18)

Publisher
American Medical Association
Copyright
Copyright © 1984 American Medical Association. All Rights Reserved.
ISSN
0003-9950
eISSN
1538-3687
DOI
10.1001/archopht.1984.01040030994034
Publisher site
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Abstract

Abstract • To determine the effect of timolol maleate on corneal epithelial wound closure, 6.4-mm (diameter) epithelial defects were created chemically in five experiments. In rabbits, wound closure was not significantly altered by the administration of 0.5% Timoptic (a commercially prepared timolol maleate solution) every eight hours, but it was inhibited during the first 15 hours of healing when a 4% solution was applied every two hours. Monkeys received a 5% solution every 12 hours and were divided into treated and control groups. Two phases of wound healing were apparent: a rapid initial phase and a slower final phase. Wound closure was inhibited in treated eyes during the initial rapid phase. This experiment repeated on the same monkeys, but with the control and treated animals switched, yielded the same result. Another experiment, with the fellow eye of the monkey used as a control, showed no significant difference in wound closure. References 1. Van Buskirk EM: Corneal anesthesia after timolol maleate therapy . Am J Ophthalmol 1979; 88:739-743. 2. Nielsen NV, Eriksen JS: Timolol: Transitory manifestations of dry eyes in long term treatment . Acta Ophthalmol 1979;57:418-424.Crossref 3. Butterfield LC, Neufeld AH: Cyclic nucleotides and mitosis in the rabbit cornea following superior cervical ganglionectomy . Exp Eye Res 1977;25:427-433.Crossref 4. Klyce SD, Neufeld AH, Zadunaisky JA: The activation of chloride transport by epinephrine and Db cyclic-AMP in the cornea of the rabbit . Invest Ophthalmol Vis Sci 1973;12:127-139. 5. Fisher F, Wiederholt M: Sodium and chloride transport in the isolated human cornea . Invest Ophthalmol Vis Sci 1975;14( (ARVO suppl) ):26. 6. Fogle JA, Neufeld AH: The adrenergic and cholinergic corneal epithelium . Invest Ophthalmol Vis Sci 1979;18:1212-1215. 7. Berridge MJ: The interaction of cyclic nucleotides and calcium in the control of cellular activity . Adv Cyclic Nucleotide Res 1975;6:1-98. 8. Jumblatt MM, Fogle JA, Neufeld AH: Cholera toxin stimulates adenosine 3',5'-monophosphate synthesis and epithelial wound closure in the rabbit cornea . Invest Ophthalmol Vis Sci 1980;19:1321-1327. 9. Jumblatt MM, Neufeld AH: Characterization of cyclic AMP-mediated wound closure of the rabbit corneal epithelium . Curr Eye Res 1981;1:189-195.Crossref 10. O'Brien WJ, DeCarlo JD, Stern M, et al: Effects of Timoptic on corneal reepithelialization . Arch Ophthalmol 1982;100:1331-1333.Crossref 11. Bartels SP, Roth HO, Jumblatt MM, et al: Pharmacological effects of timolol in the rabbit eye . Invest Ophthalmol Vis Sci 1980;19:1190-1197. 12. Zimmerman TJ, Kaufman HE: Timolol: A β-adrenergic agent for the treatment of glaucoma . Arch Ophthalmol 1977;95:601-604.Crossref 13. Cintron C, Hassinger L, Kublin CL, et al: A simple method for the removal of rabbit and corneal epithelium utilizing n-heptanol . Ophthalmic Res 1979;11:90-96.Crossref 14. Ubels JL, Edelhauser HF, Austin KH: A comparison of healing of corneal epithelial wounds stained with fluorescein or Richardson's stain . Invest Ophthalmol Vis Sci 1982;23:127-31. 15. Vareilles P, Silverstone D, Plazonnet B, et al: Comparison of the effects of timolol and other adrenergic agents on intraocular pressure in the rabbit . Invest Ophthalmol Vis Sci 1977;16:987-996. 16. Katz IM, Hubbard WA, Getson AJ, et al: Intraocular pressure decrease in normal volunteers following timolol ophthalmic solution . Invest Ophthalmol Vis Sci 1976;15:489-492.

Journal

Archives of Ophthalmology – American Medical Association

Published: Aug 1, 1984

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