Retinal organoids and stem cell therapy for vision restoration: current progress, persistent challenges, and future directions.
TL;DR
A comprehensive assessment of advancements and challenges in PSCs, MSCs, RPCs, and RPE, a methodical examination of the disparity between structural engraftment and genuine functional integration, and a cohesive discourse on innovative strategies such as optogenetics, 3D bioprinting, and extracellular vesicle-based therapies are presented.
Abstract
Vision restoration is a vital yet challenging objective in ophthalmology, as traditional therapies cannot reverse irreversible retinal damage. This issue is of significant concern, considering that millions globally are afflicted by untreatable degenerative conditions such as retinitis pigmentosa (RP) and age-related macular degeneration. Stem cell treatments and retinal organoid (RO) technology have emerged as revolutionary methodologies. ROs derived from pluripotent stem cells (PSCs) autonomously form three-dimensional (3D) laminar structures that mimic the natural human retina, providing exceptional platforms for disease modeling, pharmacological screening, and cellular replacement. Clinical studies indicate that retinal pigment epithelium (RPE) transplantation enhances visual function. In contrast, PSC-derived mesenchymal stem cells (MSCs), retinal progenitor cells (RPCs), and RPE grafts have neuroprotective and regenerative capabilities in preclinical and early-phase trials. Notwithstanding this advancement, several challenges remain, including suboptimal cell survival, insufficient functional synaptic integration, immunological rejection, tumorigenic potential, and the absence of standardized production processes. This article presents three unique contributions, diverging from previous reviews that focus solely on positive outcomes: (1) a comprehensive assessment of advancements and challenges in PSCs, MSCs, RPCs, and RPE; (2) a methodical examination of the disparity between structural engraftment and genuine functional integration; and (3) a cohesive discourse on innovative strategies such as optogenetics, 3D bioprinting, and extracellular vesicle-based therapies. We consolidate recent clinical discoveries, highlight persistent obstacles, and provide a roadmap for the future. Growing evidence suggests that, despite significant obstacles, effective retinal regeneration is gradually becoming a reality.