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Hongbo Yin, Qiaozhi Lu, Xiaokun Wang, Jennifer Elisseeff; Particulated extracellular matrix as immunomodulators for corneal wound healing. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1293.
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© ARVO (1962-2015); The Authors (2016-present)
Extracellular matrix (ECM) is essential during wound repair, as it provides the structural integrity and regulates cellular functions via the actions of cytokines and growth factors. Corneal wound healing is a complex process that involves ECM remodeling and immunomodulation. Here we reported the effects of administering particulated decellularized ECM (pdECM) from porcine lymph nodes in reducing corneal scarring after manual superficial keratectomy (MSK).
Porcine lymph nodes were decellularized, lyophilized and cryomilled to obtain microparticles. Young white rabbits were used as the animal model and fibrin glue (FG) was administered on wounded corneas as the standard treatment. For each rabbit, MSK was performed on one eye to remove 150 μm of anterior cornea and the other cornea was left unwounded as the healthy control. The animals were divided into three groups: FG, FG encapsulated with pdECM and no treatment. Photos of healthy and wounded corneal were taken regularly to examine the epithelial healing and cornea haze. Corneal samples were harvested at both one week and one month. Real-time PCR and immunohistochemistry were performed to evaluate the wound healing outcomes and scar formation.
The reepithelialization was complete within 5 days in all three groups. Treated groups had significantly reduced corneal haze scores compared to untreated corneas, and the addition of pdECM had even better effect than FG alone. pdECM was able to even further decrease the expression of both inflammatory factors (MMP9 and TNFα) at early stage (one week) and fibrosis-related genes (collagen I, TGFβ1 and CTGF) at the later stage (one month) compared to the FG group. pdECM could better maintain the corneal thickness and the normal morphology of epithelium as seen in H&E staining as well. Immunohistochemistry with CD11b demonstrated fewer macrophages infiltrations with pdECM, which also significantly downregulated the αSMA expression in regenerated corneal stroma.
pdECM is promising in modulating corneal wound healing after MSK via reducing the expression of proinflammatory cytokines and regulating the migration of immune cells during the wound healing process. pdECMplay a key role in modulating the regenerative process and is potentially a new therapeutic in affiliating the scarlesshealing after corneal surgery.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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