Novel Insight into the Inflammatory and Cellular Responses Following Experimental Glaucoma Surgery: A Roadmap for Inhibiting Fibrosis
2013
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. 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. Given that the
cellular and molecular targets that govern the early and late phases of wound healing are distinct and time
sensitive, a multi-targeted therapeutic approach to sequentially inhibit inflammation and fibrogenesis at the
critical time point may lead to improved surgical outcomes in glaucoma filtration surgery.
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