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  • c Kit RP http www apexbt com media diy images

    2018-11-08

    c-Kit+ RPCs are distributed from the central to the peripheral regions of the retina, but not in the ciliary bodies, which were previously proposed to house retinal progenitors (Cicero et al., 2009; Martinez-Navarrete et al., 2008). These data suggest that c-Kit+ RPCs are a distinct population of proton pump inhibitors list from previously described progenitors. One other location suggested to contain RPCs (in zebrafish and goldfish) is the basal side of the retinal INL (Raymond and Hitchcock, 2000; Wu et al., 2001), which is mainly composed of Müller cells and amacrine cells. c-Kit+ cells were previously identified in the INL of the mouse retina (Morii et al., 1994), but the majority of dividing c-Kit+ cells did not co-express markers of amacrine cells (Koso et al., 2007). Our current data demonstrate that c-Kit+ cells do not co-stain with Calb, ChAT or GAD, which label most GABAergic amacrine cells. However, to date there are 33 different subtypes of amacrine cells that have been identified in the rodent retina (Balasubramanian and Gan, 2014; Cherry et al., 2009; MacNeil and Masland, 1998). They are divided into two major subpopulations, GABAergic and glycinergic types, and a small population of neither GABAergic nor glycinergic amacrine cells. In the present study, we cannot exclude the possibility that c-Kit+ cells may generate a subpopulation of amacrine cells. In the future, it will be interesting to further investigate whether amacrine cells are downstream of c-Kit+ cell differentiation, as Koso and colleagues have hypothesized that a population of non-dividing c-Kit+ cells may represent a subset of amacrine cells during development (Koso et al., 2007). It is also noteworthy that Chen and colleagues recently reported that amacrine cells expressing leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) possess regeneration potential in the adult mouse retina (Chen et al., 2015). Importantly, the c-Kit-specific fate mapping studies indicate that significant subpopulations of photoreceptors in the ONL, and bipolar cells, horizontal cells, amacrine cells and Müller cells in the INL, are the progeny of c-Kit+ cells in vivo. The magnitude of c-Kit-derived cells in the retinas of mice receiving TAM over a 3.5month period, and the evidence of cell death in the ONL and proliferation in the INL, may suggest there is a level of injury amplifying the number of c-Kit-derived cells. However, we have no evidence that TAM is inducing expression of c-Kit at the mRNA or protein level in mature cells. Beyond the possibility of isolating retinal c-Kit+ cells for cell therapy, it will be critical to further explore disease models producing damage in the retinas of these lineage tracing mice to determine the potential role of endogenous c-Kit+ RPCs in retinal repair after injury in vivo. Furthermore, another important issue raised by these studies is the origin of c-Kit-derived progenitor cells in the mouse retina. Elegant studies have been performed by Hatzistergos and colleagues on the origin of c-Kit-expressing progenitor cells in the heart, with evidence that the cells originate, in part, from cardiac neural crest cells (Hatzistergos et al., 2015). From our analysis of the c-Kit+ retinal cells by flow cytometry, they are not of hematopoietic or vascular origin, and do not fulfill the criteria of mesenchymal stem/stromal cells (Supp. Fig. 6). However, additional studies will need to be performed to understand the specific origin of c-Kit+ cells in the mouse retina.
    Conclusions Taken together, our findings verify the presence of c-Kit+ RPCs in postnatal and adult mice, and these cells are self-renewing, clonogenic, and multipotent. Our data also advocate that c-Kit+ cells support the homeostasis of cells in the retina. The progeny of c-Kit+ cells contribute to retinal neurons and glial cells responsible for transmission of visual signals from the ONL, through the INL and GCL into the brain. Moreover, we propose that the ability to specifically isolate a homogeneous population of cells using c-Kit as a marker, and expanding these cells in vitro, will provide future cell therapeutic strategies for retinal diseases.