Stem cell-based therapies for neuroretinal degeneration: current landscape and future perspectives

Retinal degenerations, comprising a heterogeneous group of disorders culminating in neuroretinal dysfunction, such as inherited retinal dystrophies (IRDs) and age-related retinal degeneration, are among the leading causes of irreversible vision loss worldwide. Restoring visual function through cell replacement therapy represents an attractive, yet challenging, strategy. Candidate retinal cell sources include retinal progenitor cells (RPCs), Müller glia, human neuroretinal stem-like cells (hNRSCs), and pluripotent stem cells (PSCs). In this review, we discuss their translational advantages and limitations, which in turn influence clinical implementation. We analyze critical manufacturing challenges, including GMP scalability, quality assurance, and ethical considerations in donor material sourcing. Experimental criteria for assessing cellular products' integration into host circuitry and their capacity to restore visual function in preclinical retinal degeneration models must account for donor maturity, host retina architecture, and immune modulation, which determine survival, synapse connectivity, and delivery requirements. Ongoing clinical trials highlight the diversity of cell replacement strategies-from fetal-derived and allogenic progenitor suspensions to laminated PSC-derived retinal sheets-with each approach presenting distinct implications for survival, true integration, and logistical complexity.