• 1.

    Birchmeier W, Birchmeier C. Epithelial-mesenchymal transitions in development and tumor progression. EXS 1995;74:115.

  • 2.

    Boyer B, Roche S, Denoyelle M, et al. Src and Ras are involved in separate pathways in epithelial cell scattering. EMBO J 1997;16:59045913.

  • 3.

    Hemavathy K, Guru SC, Harris J, et al. Human slug is a repressor that localizes to sites of active transcription. Mol Cell Biol 2000;20:50875095.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Hemavathy K, Ashraf SI, Ip YT. Snail/slug family of repressors: slowly going into the fast lane of development and cancer. Gene 2000;257:112.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Savagner P. Leaving the neighborhood: molecular mechanisms involved during epithelial-mesenchymal transition. Bioessays 2001;23:912923.

  • 6.

    Caulin C, Scholl FG, Frontelo P, et al. Chronic exposure of cultured transformed mouse epidermal cell to transforming growth factor-beta 1 induces an epithelial-mesenchymal transdifferentiation and a spindle tumoral phenotype. Cell Growth Differ 1995;6:10271035.

    • Search Google Scholar
    • Export Citation
  • 7.

    Bement WM, Forscher P, Mooseker MS. A novel cytoskeletal structure involved in purse string wound closure and cell polarity maintenance. J Cell Biol 1993;121:565578.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Chandler HL, Colitz CMH, Lu P, et al. The role of the slug transcription factor in cell migration during corneal re-epithelialization in the dog. Exp Eye Res 2007;84:400411.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Savagner P, Kusewitt DF, Carver EA, et al. Developmental transcription factor slug is required for effective re-epithelialization by adult keratinocytes. J Cell Physiol 2005;202:858866.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    Nakamura K, Kurosaka D, Yoshino M, et al. Injured corneal epithelial cells promote myodifferentiation of corneal fibroblasts. Invest Ophthalmol Vis Sci 2002;43:26032608.

    • Search Google Scholar
    • Export Citation
  • 11.

    SundarRaj N, Rizzo JD, Anderson SC, et al. Expression of vimentin by rabbit corneal epithelial cells during wound repair. Cell Tissue Res 1992;267:347356.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Yu FX, Gipson IK, Guo Y. Differential gene expression in healing rat corneal epithelium. Invest Ophthalmol Vis Sci 1995;36:19972007.

  • 13.

    Suzuki K, Tanaka T, Enoki M, et al. Coordinated reassembly of the basement membrane and junctional proteins during corneal epithelial wound healing. Invest Ophthalmol Vis Sci 2000;41:24952500.

    • Search Google Scholar
    • Export Citation
  • 14.

    Han G, Lu SL, Li AG, et al. Distinct mechanisms of TGF-beta1-mediated epithelial-to-mesenchymal transition and metastasis during skin carcinogenesis. J Clin Invest 2005;115:17141723.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15.

    Imanishi J, Kamiyama K, Iguchi I, et al. Growth factors: importance in wound healing and maintenance of transparency of the cornea. Prog Retin Eye Res 2000;19:113129.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Gilger BC, Bentley E, Ollivier FJ. Diseases and surgery of the canine cornea and sclera. In: Gelatt KN, ed. Veterinary ophthalmology. 4th ed. Ames, Iowa: Blackwell Publishing, 2007;701705.

    • Search Google Scholar
    • Export Citation
  • 17.

    Kirschner SE, Niyo Y, Betts DM. Idiopathic persistent corneal erosions: clinical and pathological findings in 18 dogs. J Am Anim Hosp Assoc 1989;25:8490.

    • Search Google Scholar
    • Export Citation
  • 18.

    Champagne E, Munger RJ. Multiple punctate keratotomy for the treatment of recurrent epithelial erosions in dogs. J Am Anim Hosp Assoc 1992;28:213216.

    • Search Google Scholar
    • Export Citation
  • 19.

    Bentley E, Abrams GA, Covitz D, et al. Morphology and immuno-histochemistry of spontaneous chronic corneal epithelial defects (SCCED) in dogs. Invest Ophthalmol Vis Sci 2001;42:22622269.

    • Search Google Scholar
    • Export Citation
  • 20.

    Schultz GS. Modulation of corneal wound healing. In: Krachmer JH, Mannis MJ, Holland EJ, eds. Cornea. St Louis: Mosby, 1997;183.

  • 21.

    Apple DJ. Cornea. In: Apple DJ, Rabb MF, eds. Ocular pathology. 5th ed. St Louis: Mosby, 1998;59116.

  • 22.

    Murphy CJ, Marfurt CF, McDermott A, et al. Spontaneous chronic corneal epithelial defects (SCCED) in dogs: clinical features, innervation, and effect of topical SP, with or without IGF-1. Invest Ophthalmol Vis Sci 2001;9:277285.

    • Search Google Scholar
    • Export Citation
  • 23.

    Morgan RV, Abrams KL. A comparison of six different therapies for persistent corneal erosions in dogs and cats. Vet Comp Ophthalmol 1994;4:3843.

    • Search Google Scholar
    • Export Citation
  • 24.

    Stanley R, Hardman C, Johnson B. Results of grid keratotomy, superficial keratectomy, and debridement for the management of persistent corneal erosions in 92 dogs. Vet Ophthalmol 1998;1:233238.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25.

    Perry HD, Kenyon KR, Lamberts DW, et al. Systemic tetracycline hydrochloride as adjunctive therapy in the treatment of persistent epithelial defects. Ophthalmology 1986;93:13201322.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26.

    Association for Research in Vision and Ophthalmology. Statement for the use of animals in ophthalmic and visual research. Available at: www.arvo.org/eweb/dynamicpage.aspx?site=arvo2&webcode=AnimalsResearch. Accessed Jul 5, 2007.

    • Search Google Scholar
    • Export Citation
  • 27.

    Plumb DC. Veterinary drug handbook. 6th ed. Ames, Iowa: Blackwell Publishing, 2009;170,331,945.

  • 28.

    Van Vlem B, Vanholder R, De Paepe P, et al. Immunomodulating effects of antibiotics: literature review. Infection 1996;24:275291.

  • 29.

    Maggs DJ. Cornea and sclera. In: Maggs DJ, Miller PE, Ofri R, eds. Slatter's fundamentals of veterinary ophthalmology. 4th ed. St Louis: Saunders Elsevier, 2008;175202.

    • Search Google Scholar
    • Export Citation
  • 30.

    Hosmer DW, Lemeshow S. Applied logistic regression. 2nd ed. New York: Wiley-Interscience Publication, 2000;3143.

  • 31.

    Bras ID, Colitz CMH, Saville WJA, et al. Posterior capsular opacification in diabetic and nondiabetic canine patients following cataract surgery. Vet Ophthalmol 2006;9:317327.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32.

    Bentley E, Murphy CJ. Thermal cautery of the cornea for treatment of spontaneous chronic corneal epithelial defects in dogs and horses. J Am Vet Med Assoc 2004;224:250253.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33.

    Brockis JG, Elliott M, Lissiman M. The rate of healing of wounds treated with ultra-violet light. Aust N Z J Surg 1965;35:108114.

  • 34.

    Gelatt KN, Gelatt JP. Chapter 8. In: Small animal ophthalmic surgery. Boston: Butterworth-Heinemann, 2001;191.

  • 35.

    Cosar CB, Cohen EJ, Rapuano CJ, et al. Tarsorrhaphy: clinical experience from a cornea practice. Cornea 2001;20:787791.

  • 36.

    Gelatt K, Samuelson D. Recurrent corneal erosions and epithelial dystrophy in the Boxer dog. J Am Anim Hosp Assoc 1982;19:453460.

  • 37.

    Seedor JA, Perry HD, McNamara TF, et al. Systemic tetracycline treatment of alkali-induced corneal ulceration in rabbits. Arch Ophthalmol 1987;105:268271.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 38.

    Shlopov BV, Stuart JM, Gumanovskaya ML, et al. Regulation of cartilage collagenase by doxycycline. J Rheumatol 2001;28:835842.

  • 39.

    Nawshad A, Lagamba D, Polad A, et al. Transforming growth factor-beta signaling during epithelial-mesenchymal transformation: implications for embryogenesis and tumor metastasis. Cells Tissues Organs 2005;179:1123.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 40.

    de Iongh RU, Wederell E, Lovicu FJ, et al. Transforming growth factor-beta-induced epithelial-mesenchymal transition in the lens: a model for cataract formation. Cells Tissues Organs 2005;179:4355.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 41.

    Lawrence DA. Transforming growth factor-beta: a general review. Eur Cytokine Netw 1996;7:363374.

  • 42.

    Kolodziejczyk SMH, Hall BK. Signal transduction and TGF-beta superfamily receptors. Biochem Cell Biol 1996;74:299314.

  • 43.

    Xu J, Lamouille S, Derynck R. TGF-beta-induced epithelial to mesenchymal transition. Cell Res 2009;19:156172.

  • 44.

    Klenkler B, Sheardown H. Growth factors in the anterior segment: role in tissue maintenance, wound healing and ocular pathology. Exp Eye Res 2004;79:677688.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 45.

    Schultz G, Khaw PT, Oxford K, et al. Growth factors and ocular wound healing. Eye 1994;8:184187.

  • 46.

    Schultz GS, Strelow S, Stern GA, et al. Treatment of alkali-injured rabbit corneas with a synthetic inhibitor of matrix metalloproteinases. Invest Ophthalmol Vis Sci 1992;33:33253331.

    • Search Google Scholar
    • Export Citation
  • 47.

    Carter RT, Kambampati R, Murphy CJ, et al. Expression of matrix metalloproteinase 2 and 9 in experimentally wounded canine corneas and spontaneous chronic corneal epithelial defects. Cornea 2007;26:12131219.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 48.

    Havener WH. Chapters 1 and 6. In: Ocular pharmacology. 2nd ed. St Louis: Mosby, 1966;9,244.

  • 49.

    Newell FW. Chapters 3 and 11. In: Ophthalmology: principles and concepts. 2nd ed. St Louis: Mosby, 1969;116.

  • 50.

    Leopold IH, Steele WH. Influence of local application of sulfonamide compounds and their vehicles on regeneration of corneal epithelium. Arch Ophthal 1945;33:463467.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 51.

    Friedenwald JS, Buschke W. The influence of some experimental variables on the epithelial movements in the healing of corneal wounds. J Cell Comp Physiol 1944;23:95107.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 52.

    Heerema JC, Friedenwald JS. Retardation of wound healing in the corneal epithelium by lanolin. Am J Ophthalmol 1950;33:14211427.

  • 53.

    Hanna C, Fraufelder FT, Cable M, et al. The effects of ophthalmic ointments on corneal wound healing. Am J Ophthalmol 1973;76:193200.

  • 54.

    Hendrix DV, Ward DA, Barnhill MA. Effects of antibiotics on morphologic characteristics and migration of canine corneal epithelial cells in tissue culture. Am J Vet Res 2001;62:16641669.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 55.

    Stern GA, Schemmer GB, Farber RD, et al. Effect of topical antibiotic solutions on corneal epithelial wound healing. Arch Ophthalmol 1983;101:644647.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 56.

    Petroutsos G, Guimaraes R, Giraud J, et al. Antibiotics and corneal epithelial wound healing. Arch Ophthalmol 1983;101:17751778.

  • 57.

    Nelson JD, Silverman V, Lima PH, et al. Corneal epithelial wound healing: a tissue culture assay on the effect of antibiotics. Curr Eye Res 1990;9:277285.

    • Crossref
    • Search Google Scholar
    • Export Citation

Advertisement

In vivo effects of adjunctive tetracycline treatment on refractory corneal ulcers in dogs

Heather L. Chandler PhD1, Anne J. Gemensky-Metzler DVM, MS, DACVO2, I. Dineli Bras DVM, MS, DACVO3, Terah E. Robbin-Webb DVM, DACVO4, William J. A. Saville DVM, PhD, DACVIM5, and Carmen M. H. Colitz DVM, PhD, DACVO6
View More View Less
  • 1 College of Optometry and Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.
  • | 2 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.
  • | 3 MedVet, 300 E Wilson Bridge Rd, Worthington, OH 43085.
  • | 4 MedVet, 300 E Wilson Bridge Rd, Worthington, OH 43085.
  • | 5 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.
  • | 6 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

Abstract

Objective—To evaluate effect of adjunctive treatment with tetracycline analogues on time to complete corneal reepithelialization in dogs with nonhealing (ie, refractory) corneal ulcers.

Design—Randomized controlled clinical trial.

Animals—89 dogs with refractory corneal ulcers.

Procedures—Corneal ulcers were treated via debridement and grid keratotomy. Dogs were assigned to receive 1 of 3 treatment regimens for up to 6 weeks: doxycycline (5 mg/kg [2.27 mg/lb], PO, q 12 h) with topically applied ophthalmic ointment containing neomycin, polymyxin B, and bacitracin (ie, triple antibiotic ointment; q 8 h); cephalexin (22 mg/kg [10 mg/lb], PO, q 12 h) with topically applied oxytetracycline ophthalmic ointment (q 8 h); or a control treatment of cephalexin (22 mg/kg, PO, q 12 h) with topically applied triple antibiotic ointment (q 8 h). Healing was monitored via measurements of the wound with calipers and evaluation of photographs obtained every 2 weeks. Treatment effectiveness was evaluated by wound healing and decreased signs of pain.

Results—The Boxer breed was overrepresented in all groups. At the 2-week time point, wound healing was significantly more common in small-breed dogs, compared with large-breed dogs. Dogs treated with oxytetracycline ophthalmic ointment had a significantly shorter healing time than did dogs receiving the control treatment. Corneal ulcers in dogs that received doxycycline PO healed more rapidly than did ulcers in dogs in the control treatment group; however, this difference was not significant.

Conclusions and Clinical Relevance—Topical tetracycline ophthalmic ointment was a safe, inexpensive, and effective adjunctive treatment for refractory corneal ulcers in dogs.

Abstract

Objective—To evaluate effect of adjunctive treatment with tetracycline analogues on time to complete corneal reepithelialization in dogs with nonhealing (ie, refractory) corneal ulcers.

Design—Randomized controlled clinical trial.

Animals—89 dogs with refractory corneal ulcers.

Procedures—Corneal ulcers were treated via debridement and grid keratotomy. Dogs were assigned to receive 1 of 3 treatment regimens for up to 6 weeks: doxycycline (5 mg/kg [2.27 mg/lb], PO, q 12 h) with topically applied ophthalmic ointment containing neomycin, polymyxin B, and bacitracin (ie, triple antibiotic ointment; q 8 h); cephalexin (22 mg/kg [10 mg/lb], PO, q 12 h) with topically applied oxytetracycline ophthalmic ointment (q 8 h); or a control treatment of cephalexin (22 mg/kg, PO, q 12 h) with topically applied triple antibiotic ointment (q 8 h). Healing was monitored via measurements of the wound with calipers and evaluation of photographs obtained every 2 weeks. Treatment effectiveness was evaluated by wound healing and decreased signs of pain.

Results—The Boxer breed was overrepresented in all groups. At the 2-week time point, wound healing was significantly more common in small-breed dogs, compared with large-breed dogs. Dogs treated with oxytetracycline ophthalmic ointment had a significantly shorter healing time than did dogs receiving the control treatment. Corneal ulcers in dogs that received doxycycline PO healed more rapidly than did ulcers in dogs in the control treatment group; however, this difference was not significant.

Conclusions and Clinical Relevance—Topical tetracycline ophthalmic ointment was a safe, inexpensive, and effective adjunctive treatment for refractory corneal ulcers in dogs.

Contributor Notes

Supported by the American Kennel Club, Canine Health Foundation.

Presented in part as an oral presentation at the 39th Annual Conference of the American College of Veterinary Ophthalmologists, Boston, October 2008.

Address correspondence to Dr. Chandler (chandler.111@osu.edu).