Endogenous retinal stem and progenitor cells (RSPCs)

Endogenous retinal stem and progenitor cells (RSPCs) are a population of multipotent cells residing within the adult eye, primarily in the ciliary epithelium and as a subset of Müller glia, that possess the potential to regenerate lost retinal neurons [1.1.1, 1.3.1, 1.4.4]. While these cells exhibit robust regenerative capacity in lower vertebrates like teleost fish, they remain largely dormant or restricted in mammals, contributing to the irreversible nature of human retinal degenerative diseases [1.1.3, 1.5.3]. Therapeutic targeting of RSPCs aims to pharmacologically awaken these cells using small molecules or biologics to stimulate their proliferation, migration into the neural retina, and subsequent differentiation into functional photoreceptors or retinal ganglion cells [1.3.2, 1.5.1]. This regenerative approach is particularly promising because it is often gene-agnostic, potentially providing a treatment for various forms of inherited retinal dystrophies, such as retinitis pigmentosa, regardless of the underlying genetic mutation [1.3.1, 1.3.4]. Current clinical candidates, such as EA-2353, are being evaluated for their ability to restore vision by leveraging this innate repair mechanism [1.3.2, 1.3.3]. However, significant challenges remain, including ensuring the precise differentiation of new neurons and their successful synaptic integration into the complex existing neural circuitry of the retina [1.1.1, 1.5.2].

Other names

Retinal progenitor cellsRetinal stem cellsMüller gliaCiliary epithelium-derived stem cellsCiliary marginal zone cells

Activation of dormant endogenous stem and progenitor cells to induce proliferation, migration, and differentiation into functional retinal neurons, such as photoreceptors.