Influence Of The Topic Use Of Mitomycin C On The Differentiation Process Of Rabbit Cornea Epithelium [influência Do Uso Tópico De Mitomicina C No Processo De Diferenciação Do Epitélio Corneano De Coelhos]
Purpose: To evaluate the effects of mitomycin C eye drops (0.2 mg/ml) on the corneal epithelium of rabbits. The changes in clinical examination, histopathologic and immunohistochemical analysis were investigated. Methods: Mitomycin C and distilled water (controls) were instilled 4 times daily for 14 consecutive days in the eyes with intact ocular surface. The ocular surface was evaluated by slit-lamp examination, during the days of the drug instillation. The animals were sacrificed on the 15th, 50th and 100th day of the experiment. The histopathologic analysis of the corneal epithelium was complemented by immunohistochemical studies using monoclonal antibodies to cytokeratins (AE1 and AE5). Results: During the use of mitomycin C eye drops mild conjunctival hiperemia was detected. It disappeared 7 days after the drug was discontinued. There was no other clinical sign by slit-lamp examination. No histopathologic alterations in the corneal epithelium were detected, epithelium continuity was observed as well as maturation and presence of atypical cells. The use of 0.02% mitomycin C not influence the differentiation pattern of the corneal epithelial cell. Conclusion: The results of this investigation, in conditions of the study, showed that 0.02% mitomycin C, instilled 4 times daily for 14 consecutive days, showed a low toxic potential regarding the intact ocular surface.673463467Thoft, R.A., Friend, J., The X, Y, Z hypothesis of corneal epithelial maintenance (1983) Invest. Ophthalmol Vis Sci, 24, pp. 1442-1443Schermer, A., Galvin, S., Sun, T.T., Differentiation-related expression of a major 64K corneal keratin in vivo and in culture suggests limbal location of corneal epithelial stem cells (1986) J Cell Biol, 103, pp. 49-62Tseng, S.C.G., Concept and application of limbal stem cells (1989) Eye, 3 (PT 2), pp. 141-157Dua, H.S., Azuara-Blanco, A., Limbal stem cells of the corneal epithelium (2000) Surv Ophthalmol, 44, pp. 415-425Jabbur, N.S., Blair, S.D., Rubinfeld, R.S., Zieske, J.D., Foster, C.S., The effect of mitomycin C on corneal limbal stem cells (1994) Invest Ophthalmol Vis Sci, 35, p. 1797Ando, H., Ido, T., Kawai, Y., Yamamoto, T., Kitazawa, Y., Inhibition of corneal epithelial wound healing. A comparative study of mitomycin C and 5-fluorouracil (1992) Ophthalmology, 99, pp. 1809-1814Frucht-Pery, J., Rozenman, Y., Mitomycin C therapy for corneal intraepithelial neoplasia (1994) Am J Ophthalmol, 117, pp. 164-168Holzchuh, N., Alves, M.R., Santo, R.M., Matayoshi, S., Kara-José, N., Efeitos do uso do colírio de mitomicina C na superfície ocular de coelhos (1997) Rev Med (São Paulo), 76, pp. 303-306Ebato, B., Friend, J., Thoft, R., Comparison of limbal and peripheral corneal epithelium in tissue culture (1988) Invest Ophthalmol Vis Sci, 29, pp. 1533-1537Calabresi, P., Parks Jr., R.E., Agentes antiproliferativos e drogas usadas na imunossupressão (1987) Goodman e Gilman: As Bases Farmacológicas da Terapêutica, pp. 817-856. , Gilman AG, Goodman LS, Rall TW, Murad F, editors. 7ed., Rio de Janeiro, Guanabara KooganAlves, M.R., Saldiva, P.H.N., Lemos, M., Kara-José, N., Efeitos do uso tópico da mitomicina C no epitélio corneano de coelhas. Análise histopatológica pela morfometria (1996) Arq Bras Oftalmol, 59, pp. 431-437Kiritoshi, A., Sundar, R.A., Thoft, R.A., Differentiation in cultured limbal epithelium as defined by keratin expression (1991) Invest Ophthalmol Vis Sci, 32, pp. 3073-3077Shapiro, M.S., Thoft, R.A., Friend, J., Parrish, R.K., Gressel, M.G., 5-fluorouracil toxicity to the ocular surface epithelium (1985) Invest Ophthalmol Vis Sci, 26, pp. 580-583Mattar, D.B., Alves, M.R., Silva, M.H.T., Kara-José, N., Estudo comparativo da ação do tiotepa e da mitomicina C na reparação do epitélio corneano, em coelhas (1994) Arq Bras Oftalmol, 57, pp. 270-273Donnenfeld, E.C., Perry, H.D., Wallerstein, A., Caronia, R.M., Kanellopoulos, A.J., Sforja, P.D., Subconjunctival mitomycin C for the treatment of ocular cicatricial pemphigoid (1999) Ophthalmology, 106, pp. 72-7
