Mitomycin C-induced reduction of keratocytes and fibroblasts after photorefractive keratectomy

Tae Im Kim, Jhang Ho Pak, Sun Young Lee, Hungwon Tchah

Research output: Contribution to journalArticle

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Abstract

PURPOSE. To investigate the effects of mitomycin C (MMC) on the number of keratocytes and the proliferation of fibroblasts after photorefractive keratectomy (PRK) and exposure to ultraviolet B (UV-B) irradiation. METHODS. The right eyes of New Zealand White rabbits in Groups 1, 2, and 3 (n = 18 each) underwent PRK to correct -10 diopters with 5 mm optical zone. Sponges soaked with 0.02% MMC were applied to the right eyes of Group 1 rabbits for 2 minutes. Antibiotic ointment was applied daily to all rabbits until the epithelium healed completely, after which 0.02% MMC eye drops were applied twice daily to the right eyes in Group 2 until 4 weeks after PRK. Three weeks after PRK, the right eyes of all the remaining rabbits were exposed to 100 mJ/cm2 C UV-B radiation. Corneal haziness was assessed biomicroscopically using the Fantes scale every 3 weeks. Six eyes of each group were each enucleated 3, 6, and 12 weeks after PRK, and tissue specimens were stained with hematoxylin and eosin and with TUNEL stain. The tissues were evaluated immunohistochemically with antibody to α-smooth muscle actin (SMA). Cellular changes in the anterior stroma and epithelial basement membrane were evaluated by electron microscopy. RESULTS. Corneal haze was observed after PRK and was aggravated by UV-B irradiation. A single intraoperative application of MMC immediately after PRK induced opacity and apoptosis of keratocytes. Twelve weeks after PRK, MMC significantly reduced corneal haze, the number of keratocytes, apoptotic cells, and fibroblasts, even after UV-B irradiation. Relatively large numbers of apoptotic and SMA-positive cells were found only in PRK-treated, non-MMC treated rabbits (Group 3), even after 12 weeks. Three weeks after PRK, dying stromal cells showed cell shrinkage, and chromatin condensation was observed in all treated groups by electron microscopy. Twelve weeks after PRK, fewer keratocytes and inflammatory cells were observed just beneath the epithelial layer in Group 1 than in any of the other groups. CONCLUSIONS. MMC is a potent inhibitor of corneal haze induced by PRK. MMC reduced the number of keratocytes and fibroblasts after PRK and UV-B irradiation. Although MMC would improve the clinical results of PRK, it has significant toxicity on corneal keratocytes, which did not disappear until 3 months after PRK.

Original languageEnglish
Pages (from-to)2978-2984
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume45
Issue number9
DOIs
Publication statusPublished - 2004 Sep 1

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Photorefractive Keratectomy
Mitomycin
Fibroblasts
Rabbits
Smooth Muscle
Actins
Electron Microscopy
Corneal Keratocytes
Ophthalmic Solutions
In Situ Nick-End Labeling
Porifera
Hematoxylin
Eosine Yellowish-(YS)
Stromal Cells
Ointments

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

@article{cafcaeb3d0b94fd29a3d0868da665851,
title = "Mitomycin C-induced reduction of keratocytes and fibroblasts after photorefractive keratectomy",
abstract = "PURPOSE. To investigate the effects of mitomycin C (MMC) on the number of keratocytes and the proliferation of fibroblasts after photorefractive keratectomy (PRK) and exposure to ultraviolet B (UV-B) irradiation. METHODS. The right eyes of New Zealand White rabbits in Groups 1, 2, and 3 (n = 18 each) underwent PRK to correct -10 diopters with 5 mm optical zone. Sponges soaked with 0.02{\%} MMC were applied to the right eyes of Group 1 rabbits for 2 minutes. Antibiotic ointment was applied daily to all rabbits until the epithelium healed completely, after which 0.02{\%} MMC eye drops were applied twice daily to the right eyes in Group 2 until 4 weeks after PRK. Three weeks after PRK, the right eyes of all the remaining rabbits were exposed to 100 mJ/cm2 C UV-B radiation. Corneal haziness was assessed biomicroscopically using the Fantes scale every 3 weeks. Six eyes of each group were each enucleated 3, 6, and 12 weeks after PRK, and tissue specimens were stained with hematoxylin and eosin and with TUNEL stain. The tissues were evaluated immunohistochemically with antibody to α-smooth muscle actin (SMA). Cellular changes in the anterior stroma and epithelial basement membrane were evaluated by electron microscopy. RESULTS. Corneal haze was observed after PRK and was aggravated by UV-B irradiation. A single intraoperative application of MMC immediately after PRK induced opacity and apoptosis of keratocytes. Twelve weeks after PRK, MMC significantly reduced corneal haze, the number of keratocytes, apoptotic cells, and fibroblasts, even after UV-B irradiation. Relatively large numbers of apoptotic and SMA-positive cells were found only in PRK-treated, non-MMC treated rabbits (Group 3), even after 12 weeks. Three weeks after PRK, dying stromal cells showed cell shrinkage, and chromatin condensation was observed in all treated groups by electron microscopy. Twelve weeks after PRK, fewer keratocytes and inflammatory cells were observed just beneath the epithelial layer in Group 1 than in any of the other groups. CONCLUSIONS. MMC is a potent inhibitor of corneal haze induced by PRK. MMC reduced the number of keratocytes and fibroblasts after PRK and UV-B irradiation. Although MMC would improve the clinical results of PRK, it has significant toxicity on corneal keratocytes, which did not disappear until 3 months after PRK.",
author = "Kim, {Tae Im} and Pak, {Jhang Ho} and Lee, {Sun Young} and Hungwon Tchah",
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language = "English",
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pages = "2978--2984",
journal = "Investigative Ophthalmology and Visual Science",
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Mitomycin C-induced reduction of keratocytes and fibroblasts after photorefractive keratectomy. / Kim, Tae Im; Pak, Jhang Ho; Lee, Sun Young; Tchah, Hungwon.

In: Investigative Ophthalmology and Visual Science, Vol. 45, No. 9, 01.09.2004, p. 2978-2984.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Mitomycin C-induced reduction of keratocytes and fibroblasts after photorefractive keratectomy

AU - Kim, Tae Im

AU - Pak, Jhang Ho

AU - Lee, Sun Young

AU - Tchah, Hungwon

PY - 2004/9/1

Y1 - 2004/9/1

N2 - PURPOSE. To investigate the effects of mitomycin C (MMC) on the number of keratocytes and the proliferation of fibroblasts after photorefractive keratectomy (PRK) and exposure to ultraviolet B (UV-B) irradiation. METHODS. The right eyes of New Zealand White rabbits in Groups 1, 2, and 3 (n = 18 each) underwent PRK to correct -10 diopters with 5 mm optical zone. Sponges soaked with 0.02% MMC were applied to the right eyes of Group 1 rabbits for 2 minutes. Antibiotic ointment was applied daily to all rabbits until the epithelium healed completely, after which 0.02% MMC eye drops were applied twice daily to the right eyes in Group 2 until 4 weeks after PRK. Three weeks after PRK, the right eyes of all the remaining rabbits were exposed to 100 mJ/cm2 C UV-B radiation. Corneal haziness was assessed biomicroscopically using the Fantes scale every 3 weeks. Six eyes of each group were each enucleated 3, 6, and 12 weeks after PRK, and tissue specimens were stained with hematoxylin and eosin and with TUNEL stain. The tissues were evaluated immunohistochemically with antibody to α-smooth muscle actin (SMA). Cellular changes in the anterior stroma and epithelial basement membrane were evaluated by electron microscopy. RESULTS. Corneal haze was observed after PRK and was aggravated by UV-B irradiation. A single intraoperative application of MMC immediately after PRK induced opacity and apoptosis of keratocytes. Twelve weeks after PRK, MMC significantly reduced corneal haze, the number of keratocytes, apoptotic cells, and fibroblasts, even after UV-B irradiation. Relatively large numbers of apoptotic and SMA-positive cells were found only in PRK-treated, non-MMC treated rabbits (Group 3), even after 12 weeks. Three weeks after PRK, dying stromal cells showed cell shrinkage, and chromatin condensation was observed in all treated groups by electron microscopy. Twelve weeks after PRK, fewer keratocytes and inflammatory cells were observed just beneath the epithelial layer in Group 1 than in any of the other groups. CONCLUSIONS. MMC is a potent inhibitor of corneal haze induced by PRK. MMC reduced the number of keratocytes and fibroblasts after PRK and UV-B irradiation. Although MMC would improve the clinical results of PRK, it has significant toxicity on corneal keratocytes, which did not disappear until 3 months after PRK.

AB - PURPOSE. To investigate the effects of mitomycin C (MMC) on the number of keratocytes and the proliferation of fibroblasts after photorefractive keratectomy (PRK) and exposure to ultraviolet B (UV-B) irradiation. METHODS. The right eyes of New Zealand White rabbits in Groups 1, 2, and 3 (n = 18 each) underwent PRK to correct -10 diopters with 5 mm optical zone. Sponges soaked with 0.02% MMC were applied to the right eyes of Group 1 rabbits for 2 minutes. Antibiotic ointment was applied daily to all rabbits until the epithelium healed completely, after which 0.02% MMC eye drops were applied twice daily to the right eyes in Group 2 until 4 weeks after PRK. Three weeks after PRK, the right eyes of all the remaining rabbits were exposed to 100 mJ/cm2 C UV-B radiation. Corneal haziness was assessed biomicroscopically using the Fantes scale every 3 weeks. Six eyes of each group were each enucleated 3, 6, and 12 weeks after PRK, and tissue specimens were stained with hematoxylin and eosin and with TUNEL stain. The tissues were evaluated immunohistochemically with antibody to α-smooth muscle actin (SMA). Cellular changes in the anterior stroma and epithelial basement membrane were evaluated by electron microscopy. RESULTS. Corneal haze was observed after PRK and was aggravated by UV-B irradiation. A single intraoperative application of MMC immediately after PRK induced opacity and apoptosis of keratocytes. Twelve weeks after PRK, MMC significantly reduced corneal haze, the number of keratocytes, apoptotic cells, and fibroblasts, even after UV-B irradiation. Relatively large numbers of apoptotic and SMA-positive cells were found only in PRK-treated, non-MMC treated rabbits (Group 3), even after 12 weeks. Three weeks after PRK, dying stromal cells showed cell shrinkage, and chromatin condensation was observed in all treated groups by electron microscopy. Twelve weeks after PRK, fewer keratocytes and inflammatory cells were observed just beneath the epithelial layer in Group 1 than in any of the other groups. CONCLUSIONS. MMC is a potent inhibitor of corneal haze induced by PRK. MMC reduced the number of keratocytes and fibroblasts after PRK and UV-B irradiation. Although MMC would improve the clinical results of PRK, it has significant toxicity on corneal keratocytes, which did not disappear until 3 months after PRK.

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