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Corneal Epithelial Wound Healing in Normal and Diabetic Rabbits Treated With Tretinoin FREE

Diane L. Hatchell, PhD; John L. Ubels, PhD; Thomas Stekiel; Hatchell
[+] Author Affiliations

Accepted for publication Aug 23, 1984.

Reprint requests to Duke University Eye Center, Box 3802, Durham, NC 27710 (Dr Hatchell).


Arch Ophthalmol. 1985;103(1):98-100. doi:10.1001/archopht.1985.01050010104029
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• The rate of corneal epithelial wound healing has been shown to be faster in diabetic than in normal rabbits when the epithelial cells are removed by scraping or freezing; both methods of epithelial removal, however, damage the basement membrane in corneas of diabetic but not normal rabbits. In this study, we compared the rate of wound healing and the increase in corneal thickness in normal and diabetic rabbits in which the epithelial cells were removed with heptanol, a method that does not damage the basement membrane in either group. In addition, the effect of tretinoin on the rate of wound healing was compared in both groups. There was no statistical difference between the rate of epithelial healing in the untreated control and in untreated diabetic eyes. Treatment with tretinoin resulted in a significant increase in the rate of healing in control but not in diabetic eyes. Corneal thickness increased in all groups after epithelial removal, but the increase was significantly less in the corneas of diabetic rabbits at 24 hours. These results indicate that tretinoin may be more effective in promoting epithelial healing in eyes of normal patients than in diabetic patients.

REFERENCES

Dohlman C:  Healing problems in the corneal epithelium . Jpn J Ophthalmol 1981;;25:131-135.
Brightbill FS, Myers FL, Bresnick GH:  Postvitrectomy keratopathy . Am J Ophthalmol 1978;;85:651-655.
Perry HD, Foulks GN, Thoft RA, et al:  Corneal complications following closed vitrectomy through the pars plana . Arch Ophthalmol 1978;;96:1401-1403.
Foulks GN, Thoft RA, Perry HD, et al:  Factors related to corneal epithelial complications after closed vitrectomy in diabetics . Arch Ophthalmol 1979;;97:1076-1079.
Mandelcorn MS, Blankenship G, Machemer R:  Pars plana vitrectomy for the management of severe diabetic retinopathy . Am J Ophthalmol 1976;;81:561-570.
Friend J, Kiorpes TC, Thoft RA:  Diabetes mellitus and the rabbit corneal epithelium . Invest Ophthalmol Vis Sci 1981;;21:317-321.
Hatchell DL, Magolan JJ, Besson MJ, et al:  Damage to the epithelial basement membrane in the corneas of diabetic rabbits . Arch Ophthalmol 1983;;101:469-471.
Hatchell DL, Pederson JH, Faculjak ML:  Susceptibility of the corneal epithelial basement membrane to injury in diabetic rabbits . Cornea 1982;;1:227-231.
Ubels JL, Edelhauser HF, Austin KH:  Healing of experimental corneal wounds treated with topically applied retinoids . Am J Ophthalmol 1983;;95:353-358.
Cintron C, Hassinger L, Kublin CL, et al:  A simple method for removal of rabbit corneal epithelium utilizing n-heptanol . Ophthalmic Res 1979;;11:90.
Mishima S, Hedbys B:  Measurement of corneal thickness with the Haag-Streit pachometer . Arch Ophthalmol 1968;;80:710-713.
Khodadoust AA, Silverstein AM, Kenyon KK, et al:  Adhesion of regenerating corneal epithelium . Am J Ophthalmol 1968;;65:339-348.
Haimann MH, Abrams GW, Edelhauser HF, et al:  The effect of intraocular irrigating solutions on lens clarity in normal and diabetic rabbits . Am J Ophthalmol 1982;;95:594-605.
Hassel J, Newsome D, DeLuca L:  Increased biosynthesis of specific glycoconjugates in rat corneal epithelium following treatment with vitamin A . Invest Ophthalmol Vis Sci 1980;;19:642-647.
Taylor HR, Kimsey RA:  Corneal epithelial basement membrane changes in diabetes . Invest Ophthalmol Vis Sci 1981;;20:548-553.
Ishii Y, Lahav M, Mukai Y:  Corneal changes in diabetic patients and streptozotocindiabetic rats: An ultrastructural correlation , abstracted. Invest Ophthalmol Vis Sci 1981;; 20( (suppl) ):154.
Schultz RO, Van Horn DL, Peters MA, et al:  Diabetic keratopathy . Trans Am Ophthalmol Soc 1981;;49:180-199.
Kenyon KR:  Recurrent corneal erosions . Int Ophthalmol Clin 1979;;19:169-195.
Savage CR Jr, Cohen S:  Proliferation of corneal epithelium induced by epidermal growth factor . Exp Eye Res 1973;;15:361-364.
Ho PC, Davis WH, Elliott JH, et al:  Kinetics of corneal epithelial regeneration and epidermal growth factor . Invest Ophthalmol 1974;; 13:804-809.
Petroutsos G, Courty J, Guimaraes R, et al:  Comparison of the effects of EGF, PFGF and EDGF on corneal epithelium wound healing . Curr Eye Res 1984;;3:593-598.
Daniele S, Frati L, Fiore C, et al:  The effect of the epidermal growth factor (EGF) on the corneal epithelium in humans . Graefes Arch Klin Exp Ophthalmol 1979;;210:159-165.
Nishida T, Nakagawa S, Nishibayashi C, et al:  Fibronectin enhancement of corneal epithelial healing of rabbits in vivo . Arch Ophthalmol 1984;;102:455-456.
Nishida T, Ohashi Y, Awata T, et al:  Fibronectin, a new therapy for corneal trophic ulcer . Arch Ophthalmol 1983;;101:1046-1048.
Phan T-M, Fujikawa LS, Colvin RB, et al:  Fibronectin does not affect epithelial migration in superficial corneal wounds , abstracted. Invest Ophthalmol Vis Sci 1984;;25( (suppl) ):78.
Ubels JL, MacRae SM:  Vitamin A is present as retinol in the tears of humans and rabbits . Curr Eye Res 1984;;3:815-822.
Tseng SCG, Hatchell DL, Tierney N, et al: Expression of specific keratin markers by rabbit corneal, conjunctival and esophageal epithelia during vitamin A deficiency-induced keratinization. J Cell Biol, in press.

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Dohlman C:  Healing problems in the corneal epithelium . Jpn J Ophthalmol 1981;;25:131-135.
Brightbill FS, Myers FL, Bresnick GH:  Postvitrectomy keratopathy . Am J Ophthalmol 1978;;85:651-655.
Perry HD, Foulks GN, Thoft RA, et al:  Corneal complications following closed vitrectomy through the pars plana . Arch Ophthalmol 1978;;96:1401-1403.
Foulks GN, Thoft RA, Perry HD, et al:  Factors related to corneal epithelial complications after closed vitrectomy in diabetics . Arch Ophthalmol 1979;;97:1076-1079.
Mandelcorn MS, Blankenship G, Machemer R:  Pars plana vitrectomy for the management of severe diabetic retinopathy . Am J Ophthalmol 1976;;81:561-570.
Friend J, Kiorpes TC, Thoft RA:  Diabetes mellitus and the rabbit corneal epithelium . Invest Ophthalmol Vis Sci 1981;;21:317-321.
Hatchell DL, Magolan JJ, Besson MJ, et al:  Damage to the epithelial basement membrane in the corneas of diabetic rabbits . Arch Ophthalmol 1983;;101:469-471.
Hatchell DL, Pederson JH, Faculjak ML:  Susceptibility of the corneal epithelial basement membrane to injury in diabetic rabbits . Cornea 1982;;1:227-231.
Ubels JL, Edelhauser HF, Austin KH:  Healing of experimental corneal wounds treated with topically applied retinoids . Am J Ophthalmol 1983;;95:353-358.
Cintron C, Hassinger L, Kublin CL, et al:  A simple method for removal of rabbit corneal epithelium utilizing n-heptanol . Ophthalmic Res 1979;;11:90.
Mishima S, Hedbys B:  Measurement of corneal thickness with the Haag-Streit pachometer . Arch Ophthalmol 1968;;80:710-713.
Khodadoust AA, Silverstein AM, Kenyon KK, et al:  Adhesion of regenerating corneal epithelium . Am J Ophthalmol 1968;;65:339-348.
Haimann MH, Abrams GW, Edelhauser HF, et al:  The effect of intraocular irrigating solutions on lens clarity in normal and diabetic rabbits . Am J Ophthalmol 1982;;95:594-605.
Hassel J, Newsome D, DeLuca L:  Increased biosynthesis of specific glycoconjugates in rat corneal epithelium following treatment with vitamin A . Invest Ophthalmol Vis Sci 1980;;19:642-647.
Taylor HR, Kimsey RA:  Corneal epithelial basement membrane changes in diabetes . Invest Ophthalmol Vis Sci 1981;;20:548-553.
Ishii Y, Lahav M, Mukai Y:  Corneal changes in diabetic patients and streptozotocindiabetic rats: An ultrastructural correlation , abstracted. Invest Ophthalmol Vis Sci 1981;; 20( (suppl) ):154.
Schultz RO, Van Horn DL, Peters MA, et al:  Diabetic keratopathy . Trans Am Ophthalmol Soc 1981;;49:180-199.
Kenyon KR:  Recurrent corneal erosions . Int Ophthalmol Clin 1979;;19:169-195.
Savage CR Jr, Cohen S:  Proliferation of corneal epithelium induced by epidermal growth factor . Exp Eye Res 1973;;15:361-364.
Ho PC, Davis WH, Elliott JH, et al:  Kinetics of corneal epithelial regeneration and epidermal growth factor . Invest Ophthalmol 1974;; 13:804-809.
Petroutsos G, Courty J, Guimaraes R, et al:  Comparison of the effects of EGF, PFGF and EDGF on corneal epithelium wound healing . Curr Eye Res 1984;;3:593-598.
Daniele S, Frati L, Fiore C, et al:  The effect of the epidermal growth factor (EGF) on the corneal epithelium in humans . Graefes Arch Klin Exp Ophthalmol 1979;;210:159-165.
Nishida T, Nakagawa S, Nishibayashi C, et al:  Fibronectin enhancement of corneal epithelial healing of rabbits in vivo . Arch Ophthalmol 1984;;102:455-456.
Nishida T, Ohashi Y, Awata T, et al:  Fibronectin, a new therapy for corneal trophic ulcer . Arch Ophthalmol 1983;;101:1046-1048.
Phan T-M, Fujikawa LS, Colvin RB, et al:  Fibronectin does not affect epithelial migration in superficial corneal wounds , abstracted. Invest Ophthalmol Vis Sci 1984;;25( (suppl) ):78.
Ubels JL, MacRae SM:  Vitamin A is present as retinol in the tears of humans and rabbits . Curr Eye Res 1984;;3:815-822.
Tseng SCG, Hatchell DL, Tierney N, et al: Expression of specific keratin markers by rabbit corneal, conjunctival and esophageal epithelia during vitamin A deficiency-induced keratinization. J Cell Biol, in press.

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