Validation of the glaucoma filtration surgical mouse model for antifibrotic drug evaluation

Mol Med. May-Jun 2011;17(5-6):557-67. doi: 10.2119/molmed.2010.00188. Epub 2011 Jan 11.

Abstract

Glaucoma is a progressive optic neuropathy, which, if left untreated, leads to blindness. The most common and most modifiable risk factor in glaucoma is elevated intraocular pressure (IOP), which can be managed surgically by filtration surgery. The postoperative subconjunctival scarring response, however, remains the major obstacle to achieving long-term surgical success. Antiproliferatives such as mitomycin C are commonly used to prevent postoperative scarring. Efficacy of these agents has been tested extensively on monkey and rabbit models of glaucoma filtration surgery. As these models have inherent limitations, we have developed a model of glaucoma filtration surgery in the mouse. We show, for the first time, that the mouse model typically scarred within 14 d, but when augmented with mitomycin C, more animals maintained lower intraocular pressures for a longer period of time concomitant with prolonged bleb survival to beyond 28 d. The morphology of the blebs following mitomycin C treatment also resembled well-documented clinical observations, thus confirming the validity and clinical relevance of this model. We demonstrate that the antiscarring response to mitomycin C is likely to be due to its effects on conjunctival fibroblast proliferation, apoptosis and collagen deposition and the suppression of inflammation. Indeed, we verified some of these properties on mouse conjunctival fibroblasts cultured in vitro. These data support the suitability of this mouse model for studying the wound healing response in glaucoma filtration surgery, and as a potentially useful tool for the in vivo evaluation of antifibrotic therapeutics in the eye.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifibrinolytic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Conjunctiva / cytology
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Filtering Surgery*
  • Glaucoma / drug therapy*
  • In Situ Nick-End Labeling
  • Mice
  • Mice, Inbred C57BL
  • Mitomycin / therapeutic use
  • Models, Biological
  • Wound Healing / drug effects

Substances

  • Antifibrinolytic Agents
  • Mitomycin