June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Novel Insight into the Inflammatory and Cellular Responses following Experimental Glaucoma Surgery: a Roadmap for Inhibiting Fibrosis
Author Affiliations & Notes
  • Li-Fong Seet
    Ocular Therapeutics & Drug Delivery, Singapore Eye Research Institute, Singapore, Singapore
    Department of Research, Duke-NUS Graduate Medical School Singapore, Singapore, Singapore
  • Tina Wong
    Ocular Therapeutics & Drug Delivery, Singapore Eye Research Institute, Singapore, Singapore
    Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
  • Footnotes
    Commercial Relationships Li-Fong Seet, PCT/SG2010000382 (P); Tina Wong, 61, 250,006 (P)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 2140. doi:
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    • Get Citation

      Li-Fong Seet, Tina Wong; Novel Insight into the Inflammatory and Cellular Responses following Experimental Glaucoma Surgery: a Roadmap for Inhibiting Fibrosis. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2140.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Failure after glaucoma filtration surgery is attributed to fibrosis at the operated site. To understand the wound healing process after glaucoma filtration surgery, we have developed a mouse model for glaucoma filtration surgery which closely mimics the clinical response. In this study, we describe a systematic analysis of the wound healing response in vivo.

Methods: Modified GFS was performed on mice. Quantitative polymerase chain reaction, antibody-based cytokine assays, flow cytometry, and immunofluorescent analyses were performed to determine gene and cellular changes. Primary subconjunctival fibroblasts were stimulated with TNF-α or TGF-β to assess their involvement in the wound healing process.

Results: Our data revealed that the post-surgical tissue response was separable into two distinguishable phases. The early “acute inflammatory” phase was characterized by significantly increased transcript expression of Vegfa, Cxcl1, Cxcl5, Ccl2, Ccl3, Ccl4, Gmcsf and specific Mmps as well as greater infiltration of monocytes/macrophages and T cells. The late “fibrotic” phase was characterized by an increased expression of Tgfb2 and extracellular matrix genes as well as a notable reduction of infiltrating inflammatory cells. Significantly more mitotic cells were observed at both time points post-surgery. Subconjunctival fibroblasts may be involved in both phases since they have the capacity to reiterate the in vivo gene expression profiles upon either pro-inflammatory or pro-fibrotic cytokine stimulation.

Conclusions: The wound healing response after GFS is separable into two distinct phases implicating the need for sequential application of therapeutics specifically targeting each phase in order to overcome the long term scarring response.

Keywords: 474 conjunctiva • 490 cytokines/chemokines • 765 wound healing  
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