Abstract
Retinal degenerative disease (RDD) refers to a group of diseases with retinal degeneration that cause vision loss and affect people’s daily lives. Various therapies have been proposed, among which stem cell therapy (SCT) holds great promise for the treatment of RDDs. Microglia are immune cells in the retina that have two activation phenotypes, namely, pro-inflammatory M1 and anti-inflammatory M2 phenotypes. These cells play an important role in the pathological progression of RDDs, especially in terms of retinal inflammation. Recent studies have extensively investigated the therapeutic potential of stem cell therapy in treating RDDs, including the immunomodulatory effects targeting microglia. In this review, we substantially summarized the characteristics of RDDs and microglia, discussed the microglial changes and phenotypic transformation of M1 microglia to M2 microglia after SCT, and proposed future directions for SCT in treating RDDs.
Highlights
The retina is a stratiform sensory tissue that consists of various cell types, including retinal pigment epithelium (RPE) cells, photoreceptors, intermediate neurons, retinal ganglion cells (RGCs) and glial cells (Malhotra et al, 2011; Madeira et al, 2015)
Numerous studies have transplanted RPE cells, photoreceptors and RGCs derived from induced pluripotent stem cells, embryonic stem cells (ESCs) and retinal progenitor cells (RPCs), and some of them have advanced to clinical trials (Liu et al, 2017; Mandai et al, 2017; Zhang et al, 2020b)
In our previous in-vivo study, by transplanting organoid-derived human RPCs (hRPCs) into the subretinal space of rat Retinal degenerative disease (RDD) models (RCS rats), we found that the number of Iba1+/CD68+ phagocytic M1 microglia was significantly lower in the transplantation group than that in the control group (Zou et al, 2019)
Summary
The retina is a stratiform sensory tissue that consists of various cell types, including retinal pigment epithelium (RPE) cells, photoreceptors, intermediate neurons, retinal ganglion cells (RGCs) and glial cells (Malhotra et al, 2011; Madeira et al, 2015). Three distinct glial cell types are present within the retina: Müller cells, astrocytes, and microglia (Vecino et al, 2016). Müller cells are responsible for providing metabolic support to retinal neurons and regulating synaptic activity (Reichenbach and Bringmann, 2013). Together with Müller cells, astrocytes integrate the vascular and neuronal activity of the retina (Kolb, 1995). The third type of retinal glial cell, are regarded as resident tissue macrophages and play important roles in retinal homeostasis (Langmann, 2007). Recent studies confirmed that SCT was likely to modulate microglial polarization toward the antiinflammatory M2 phenotype (Jha et al, 2018). Assumptions that SCT may be better used to treat RDDs by targeting microglial polarization are discussed
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