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Cellular therapy for open angle glaucoma with emphasis on mesenchymal stem cells secretome induced trabecular meshwork regeneration

  • C.T. Tebid
    Affiliations
    Immuno-oncology/Opthalmology, CrHMR, Montreal, Quebec, Canada

    Biology, Concordia University, Montreal, Quebec, Canada

    Opthalmology, CrHMR, Montreal, Quebec, Canada

    Immuno-oncology, CrHMR, Montreal, Quebec, Canada
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      Primary open-angle glaucoma (POAG) is the most common form of glaucoma and constitutes one of the leading causes of irreversible blindness in the world. It is characterized by gradual degeneration of the optic nerves stemming from an increase in the intraocular pressure (IOP). Functional abnormalities in the trabecular meshwork (TM), an exit channel for aqueous humor (AH) liquid, leads to the accumulation of AH in the anterior chamber of the affected eye leading to increase in IOP. At present, there is no effective treatment for curing the disease. Current therapeutic modalities of POAG, pharmacological and surgical, aim at relieving the IOP and slow the progression of the disease, and are short lived. Consequently, regeneration of the TM cells may represent an effective treatment that may not only prevent the progression but reverse the disease as well. We previously demonstrated the regenerative effects of Mesenchymal stem cell conditioned media (MSC-CM) in proliferation of neuronal progenitor cells and tissue regeneration in laser damaged TM area leading to decrease in IOP in rat model of glaucoma partly due to macrophage recruitment. In the current study, we have investigated the mechanism of MSC-CM educated macrophages mediated tissue regeneration. To this end, we have taken a proteomic approach to identify potential wound healing factors that may be present in MSC-CM and produced by MSC-CM educated macrophages. Based on the proteomic data, we have generated a protein-actome and are testing various pathways, the effect of DCR1 produced by MSC-CM educated macrophages on IOP, the activation and proliferation of neuronal progenitor cells present in the TM area following injection of DCR1 into laser damaged rat eyes. Interestingly, the inhibition of DCR1 annuls the healing effect of DCR1. Furthermore, the injection of DCR1 alone resulted in >50% decrease in IOP in laser-induced glaucoma rats, thus, demonstrating the importance of DCR1 in the healing process. This result suggest that DCR1 stands as one of the major drivers in the regenerative process by MSC-CM educated macrophages. In summary, this regenerative potential of MSC-CM educated macrophage on the TM could be translated into cellular therapy based approach for the treatment of POAG.
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