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Introduction Visional signals are mediated by photoreceptors, bipolar EPZ015666 cost and ganglion cells, and the loss of these neurons leads to irreversible blindness (de Jong, 2006; Friedman et al., 2004; Hartong et al., 2006; Quigley and Broman, 2006; Ramsden et al., 2013; Thylefors et al., 1995). Photoreceptors are the light sensor of the outer nuclear layer (ONL) of the retina, and degeneration and death of these cells occur with retinitis pigmentosa, a disease that affects 1/3000–4000 individuals younger than 60years of age (Hartong et al., 2006). Age-related macular degeneration (AMD), a major cause of blindness in people over 50years, is characterized by dysfunction of the retinal pigment epithelium (RPE) followed by apoptosis of photoreceptors (de Jong, 2006; Friedman et al., 2004). The high ocular pressure of glaucoma (Quigley and Broman, 2006), or the ischemic retinopathy of diabetes (Antonetti et al., 2012), also results in the loss of functional retinal cells leading to impaired vision. Bipolar cells of the retinal inner nuclear layer (INL) transmit the visional signal from the photoreceptors to the ganglion cells and then into the brain. In addition to neurons, RPE and Müller glial cells support the nutrition and homeostasis of the retina (Goldman, 2014; Ramsden et al., 2013; Reichenbach and Bringmann, 2013). Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been used to generate RPE for the treatment of AMD, preventing its progression by protecting the underlying photoreceptors(Mead et al., 2015). However, the photoreceptors that have been lost in AMD still require replacement. The use of retinal progenitor cells (RPCs) for neuronal regeneration is an active area of investigation; although progress has been challenging due to the lack of specific surface markers for isolation of RPCs, and the fact that previously identified RPCs are a heterogeneous population of cells(Ahmad et al., 2000; Cepko, 2014; Gualdoni et al., 2010; MacLaren et al., 2006; Tropepe et al., 2000). Thus, the differentiation potential of individual progenitor cells has been difficult to evaluate. ESCs and iPSCs are capable of generating precursors of photoreceptors in vitro, but transplantation of these precursors in vivo has had limited success (Binder, 2011; Mead et al., 2015; Schwartz et al., 2012). Moreover, ESCs and iPSCs need to be differentiated prior to implantation in vivo, to avoid the risk of tumorigenesis (Cui et al., 2013; Shirai et al., 2016; West et al., 2012). Following lineage specification, ESCs and iPSCs lose their integration capacity and their multipotent phenotype, which limits their therapeutic potential(West et al., 2012). To our knowledge, a population of cells that expresses a stem/progenitor cell antigen and maintains the self-renewing and multipotent characteristics of a stem/progenitor cell in vivo is critical. The lack of a specific surface marker that allows for isolation and expansion of live progenitor cells from the eye, has been an issue preventing identification of a primitive cell capable of regulating physiologic cell renewal and organ reconstitution following injury. The stem cell factor receptor c-Kit, also known as tyrosine-protein kinase Kit or CD117, is a protein involved in the development, maturation, and survival of neurons (Hirata et al., 1993; Jin et al., 2002). Both c-Kit and Kit ligand, stem cell factor, are present on cell surface membranes of neuronal cells in the central nervous system, including retinas of mice and humans (Das et al., 2004; Hasegawa et al., 2008; Koso et al., 2007; Mochizuki et al., 2014; Morii et al., 1994; Zhou et al., 2015), and the peripheral nervous system (Goldstein et al., 2015; Guijarro et al., 2013; Sachewsky and Morshead, 2014). c-Kit-positive (c-Kit+) cells have also recently been identified from the retinal neuroblast layer of human eyes (embryonic weeks 12–14), and are being proposed as RPCs with the potential for application in retinal degeneration without tumorigenesis (Chen et al., 2016; Zhou et al., 2015). However, it is not known whether c-Kit+ cells with progenitor cell properties exist in the postnatal or adult retina, and whether progeny of these cells contribute to the architecture of the retina. The expression of c-Kit has been employed previously for the identification and characterization of hematopoietic, cardiac, and lung stem/progenitor cells (Bolli et al., 2011; Itkin et al., 2012; Kajstura et al., 2011), suggesting that the presence of c-Kit may uncover a pool of resident RPCs critical for the maintenance of neuronal cells responsible for vision.