Abstract
Glaucoma represents a group of progressive optic neuropathies characterized by gradual loss of retinal ganglion cells (RGCs), the neurons that conduct visual information from the retina to the brain. Elevated intraocular pressure (IOP) is considered the main reason for enhanced apoptosis of RGCs in glaucoma. Currently used therapeutic agents are not able to repopulate and/or regenerate injured RGCs and, therefore, are ineffective in most patients with advanced glaucoma. Accordingly, several new therapeutic approaches, including stem cell-based therapy, have been explored for the glaucoma treatment. In this review article, we emphasized current knowledge regarding molecular and cellular mechanisms responsible for beneficial effects of mesenchymal stem cells (MSCs) and their secretome in the treatment of glaucoma. MSCs produce neurotrophins and in an exosome-dependent manner supply injured RGCs with growth factors enhancing their survival and regeneration. Additionally, MSCs are able to generate functional RGC-like cells and induce proliferation of retinal stem cells. By supporting integrity of trabecular meshwork, transplanted MSCs alleviate IOP resulting in reduced loss of RGCs. Moreover, MSCs are able to attenuate T cell-driven retinal inflammation providing protection to the injured retinal tissue. In summing up, due to their capacity for neuroprotection and immunomodulation, MSCs and their secretome could be explored in upcoming clinical studies as new therapeutic agents for glaucoma treatment.
Highlights
Glaucoma, a complex, multifactorial eye disease, is a leading cause of irreversible blindness affecting more than 70 million people worldwide [1]
In accordance with the criteria set by the International Society for Cellular Therapy, a cell population has to fulfill following criteria to be defined as mesenchymal stem cells (MSCs): (a) must adhere to plastic in standard culture conditions; (b) must be able to differentiate into adipocytes, osteoblasts, and chondrocytes under standard in vitro differentiating conditions; and (c) more than 95% of the cell population must express CD105, CD73 (SH3/4, ectoenzyme, regulates the purinergic signaling through the hydrolysis of adenosine triphosphate), and CD90 (Thy-1, regulates differentiation) and must lack expression of CD45, CD34, CD14 or CD11b, CD79a or CD19, and HLA class II, which are membrane markers of leukocytes, thrombocytes, or erythrocytes [29]
amniotic fluid-derived MSCs (AF-MSCs)-Exos selectively downregulated Janus kinase/Stat signaling pathways in inflammatory T cells without affecting expansion and immunosuppressive properties of CD4+CD25+FoxP3+ T regulatory cells [68], indicating their therapeutic use in the treatment of T cell-driven inflammatory diseases, including glaucoma. In line with these findings, we recently developed neuroprotective and immunomodulatory ophthalmic solution (“Exosome-Derived Multiple Allogeneic Protein Paracrine Signaling (Exosomes D-MAPPS)”) which activity is based on the capacity of AF-MSC-derived exosomes to produce neurotrophins (PDGF, nerve growth factor (NGF)) and immunomodulatory factors (TGF-β, hepatocyte growth factor (HGF)) enabling tissue repair in neurodegenerative and inflammatory eye diseases [5, 67, 68]
Summary
A complex, multifactorial eye disease, is a leading cause of irreversible blindness affecting more than 70 million people worldwide [1]. It represents a group of progressive optic neuropathies characterized by gradual loss of retinal ganglion cells (RGCs), the neurons that conduct visual information from the retina to the brain [2]. Several new therapeutic approaches have been investigated for recovering from blindness or for maintenance of remaining vision in glaucoma [4]. Because of their functional properties, mesenchymal stem cells (MSCs) have. Eligible studies had to delineate molecular and cellular mechanisms involved in the MSCbased therapy of glaucoma, and their findings were analyzed in this review
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