Molecular Medicine

, Volume 17, Issue 5–6, pp 557–567 | Cite as

Validation of the Glaucoma Filtration Surgical Mouse Model for Antifibrotic Drug Evaluation

  • Li-Fong Seet
  • Wing Sum Lee
  • Roseline Su
  • Sharon N Finger
  • Jonathan G Crowston
  • Tina T Wong
Research Article


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.



We thank Hla Myint Htoon (Singapore Eye Research Institute) for help with the statistical analysis and the Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, for help with the polarizing microscopy. This work was supported by the National Research Foundation Council Translational and Clinical Research (TCR) Programme Grant (NMRC/TCR/002-SERI/2008) and a research grant from the National Medical Research Council (NMRC/EDG/0019/2008) to TT Wong.


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Copyright information

© The Feinstein Institute for Medical Research 2011

Authors and Affiliations

  • Li-Fong Seet
    • 1
  • Wing Sum Lee
    • 1
  • Roseline Su
    • 1
  • Sharon N Finger
    • 1
  • Jonathan G Crowston
    • 2
  • Tina T Wong
    • 1
    • 3
    • 4
    • 5
  1. 1.Ocular Wound Healing and TherapeuticsSingapore Eye Research InstituteSingaporeSingapore
  2. 2.Centre for Eye Research AustraliaRoyal Victorian Eye and Ear HospitalMelbourneAustralia
  3. 3.Glaucoma ServiceSingapore National Eye CenterSingaporeSingapore
  4. 4.Department of Ophthalmology, Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
  5. 5.School of Materials Science and EngineeringNanyang Technological UniversityNanyangSingapore

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