Extraocular Application of Mitomycin C in a Rabbit Model: Cytotoxic Effects on the Ciliary Body and Epithelium

Nepafenac ophthalmic suspension is a topical non-steroidal anti-inflammatory drug (NSAID) approved in the US and Europe for prevention and treatment of post-operative pain and inflammation associated with cataract surgery, and recently approved in Europe for reduction in risk of post-operative macular oedema associated with cataract surgery in diabetic patients. Unlike conventional NSAIDs, nepafenac is a prodrug that is uncharged and this results in great corneal permeability. Experimental studies on nepafenac demonstrated enhanced permeability compared with other NSAIDs, and rapid bioactivation to amfenac by intraocular hydrolases within ocular tissues including ciliary body epithelium, retina, choroid and cornea, which results in targeted delivery of active drug to anterior and posterior segments. Furthermore, these study results have been confirmed in clinical trials. Nepafenac may have prolonged activity in vascularised tissues of the eye because bioconversion is targeted to the iris/ciliary body, and to a greater extent the retina and choroid. Nepafenac and amfenac are potent inhibitors of cyclo-oxygenase (COX) enzyme isoforms, COX-1 and COX-2. Topical nepafenac penetrated into the posterior segment in a rabbit model of concanavalin-A induced retinal inflammation, where it diminished vitreous protein and prostaglandin E2concentrations and reduced breakdown of the blood–retinal barrier. Other NSAIDs, including ketorolac, failed to reduce the increase of these inflammatory markers in the same study. A randomised clinical study showed that based on retinal thickening and vision, treatment with nepafenac beginning pre-surgery and used for up to 90 days post-cataract surgery is effective in preventing macular oedema and associated loss of visual acuity in diabetic patients.

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Morphologic proof of the toxicity of mitomycin C on the ciliary body in relation to different application methods

Graefe s Archive for Clinical and Experimental Ophthalmology ◽

10.1007/s004170050283 ◽

1999 ◽

Vol 237 (7) ◽

pp. 593-600 ◽

Cited By ~ 18

Author(s):

U. Schraermeyer ◽

M. Diestelhorst ◽

A. Bieker ◽

M. Theisohn ◽

H. Mietz ◽

...

Keyword(s):

Mitomycin C ◽

Ciliary Body ◽

Application Methods

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959. bcl-2 Antisense Oligonucleotides Enhance the Cytotoxic Effects of Mitomycin C in the Treatment of Bladder Cancer

Molecular Therapy ◽

10.1016/j.ymthe.2004.06.902 ◽

2004 ◽

Vol 9 ◽

pp. S366-S367

Keyword(s):

Bladder Cancer ◽

Mitomycin C ◽

Antisense Oligonucleotides ◽

Cytotoxic Effects

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Chidamide and mitomycin C exert synergistic cytotoxic effects against bladder cancer cells in vitro and suppress tumor growth in a rat bladder cancer model

Cancer Letters ◽

10.1016/j.canlet.2022.01.007 ◽

2022 ◽

Author(s):

Shao-Chuan Wang ◽

Chia-Ying Yu ◽

Yao-Cheng Wu ◽

Ya-Chuan Chang ◽

Sung-Lang Chen ◽

...

Keyword(s):

Bladder Cancer ◽

Tumor Growth ◽

Cancer Cells ◽

Mitomycin C ◽

Cancer Model ◽

Cytotoxic Effects ◽

Rat Bladder ◽

Bladder Cancer Cells ◽

Bladder Cancer Model

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Delayed Development of Limbal Stem Cell Deficiency Following Chemical Injury—Pathogenesis and Therapeutic Strategies

US Ophthalmic Review ◽

10.17925/usor.2013.06.02.101 ◽

2013 ◽

Vol 06 (02) ◽

pp. 101

Author(s):

Tamar Kadar ◽

Shlomit Dachir ◽

Vered Horwitz ◽

Adina Amir ◽

◽

...

Keyword(s):

Stem Cell ◽

Sulfur Mustard ◽

Rabbit Model ◽

Therapeutic Window ◽

Epithelial Stem Cells ◽

Proliferating Cells ◽

Ocular Surgery ◽

Cytotoxic Effects ◽

Warfare Agents ◽

Slow Cycling

Limbal epithelial stem cell deficiency (LSCD) occurs as a result of damage to the limbal epithelial stem cells (ESC) population. It may derive from direct destructive loss of the ESC (common chemical burn), and/or from dysfunction of the SC niche, leading to delayed death of the cells. This review focuses on delayed-onset LSCD, induced by antineoplastic chemicals, such as mitomycin C, 5-fluorouracil, and mustards, in terms of pathogenesis and management. These agents are used in ocular surface chemotherapy, in ocular surgery procedures, and as warfare agents, and target proliferating cells as slow-cycling cells, such as the ESC, are relatively resistant. Although the mechanism of the delayed loss of ESC is not entirely clear, we have shown, in the rabbit model, pathologic alterations in the limbal stroma, following the application of sulfur mustard, suggesting that dysfunction of the niche triggers the death of the SC later on. The absence of direct cytotoxic effects of these agents on the ESC, indicates a therapeutic window for prevention of the delayed LSCD.

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