Abstract
The dome-shaped cornea is a transparent, non-vascularized, and epithelialized highly organized tissue. Physical and chemical injuries may trigger corneal wound healing (CWH) response and result in neovascularization that impairs the visual function. CWH involves not only migration, proliferation, and differentiation of the cells in different layers of cornea, but also the mobilization of immune cells. We demonstrated here that human adipose-derived mesenchymal stromal cells (ADSCs) could effectively inhibit neovascularization during ethanol-induced injury in mouse cornea. Importantly, we found that while neutrophils are essential for CWH, excessive and prolonged neutrophil retention during the granulation stage contributes to neovascularization. ADSCs were found to promote the clearance of neutrophils in the cornea during the granulation stage, likely via increasing the reverse transendothelial cell migration of CXCR4high neutrophils from cornea to the lung. Our results demonstrate that ADSCs are effective in treating CWH-induced neovascularization and modulation of neutrophil clearance could be novel strategies for better vision recovery after injury.
Highlights
In addition to protecting the interior structure of the eye from environmental insults, the dome-shaped cornea acts as a lens to focus light entering the eye
Our results demonstrated an antiangiogenic function of adipose-derived mesenchymal stromal cells (ADSCs) during corneal wound healing (CWH) and that promoting the reverse migration of neutrophils could be a new approach for the treatment of corneal injury
To eliminate the interference of tunicae vasculosa, the whole cornea was removed for CD31 immunofluorescence staining and revealed tubular structures on the cornea of the EtOH group, whereas such structure is less apparent and exhibited weaker staining in the EtOH + ADSCs group (Fig. 1e)
Summary
In addition to protecting the interior structure of the eye from environmental insults, the dome-shaped cornea acts as a lens to focus light entering the eye. The latter function of the cornea depends on its precise radians and flawless transparency. Because CWH is often accompanied by Previous studies suggest that each of these steps is closely associated with neovascularization[5,6,7,8,9], the kinetics of this process is not fully described. A better understanding of the pathophysiological process involved in CWH can help to identify the key steps involved in corneal neovascularization. MSCs contribute to tissue homeostasis and Official journal of the Cell Death Differentiation Association
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