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Patient-specific Neural Progenitor Therapy Preserves Visual Function

Review of “Human iPSC-Derived Neural Progenitors Preserve Vision in an AMD-Like Model” from Stem Cells by Stuart P. Atkinson

Stem cell transplantation for the treatment of retinal degenerative diseases currently represents one if the most promising therapeutic avenues in the battle against blindness. The laboratory of Shaomei Wang (Cedars-Sinai Medical Center, Los Angeles) have assessed the effectiveness of these strategies using the Royal College of Surgeons (RCS) rat model which mimics the disease progression of age-related macular degeneration (AMD). This includes the disruption of the retinal pigment epithelium (RPE) and the subsequent death of photoreceptors [1]. Their studies concluded that human cortical-derived neural progenitor cells (hNPCctx) could dramatically rescue vision in the RCS rat [2, 3] although their fetal origin represented an obstacle for their widespread use. 

To bypass these obstacles, the group have now assessed if a stable neural progenitor cell line (iNPCs) derived from induced pluripotent stem cells (iPSCs) [4] could preserve vision after sub-retinal injection into RCS rats. Encouragingly, they now report in Stem Cells that iNPC injection leads to the reversal of AMD-related symptoms, the preservation of visual function, and may represent a patient-specific therapeutic option [5].

The authors began the study by showing that an iNSC-treated eye scored higher in all functional tests used (optokinetic response (OKR), electroretinography (ERG), and luminance threshold responses (LTR)), compared to a contralateral untreated eye, in RCS mice at 150 days post-transplant. This improvement  correlated to the improved protection of photoreceptors in iNPC-treated eyes (See figure - black arrows indicate photoreceptor layers), which presented with normal cone morphology and the reversal of disease-associated changes throughout the retina.

So how are iNPCs influencing the preservation of photoreceptors and visual function? The study found that iNPCs survived up to 130 days in RCS retinas, which when normalized to lifespan, represents around 16 years in humans. Furthermore, the study also found that iNPCs were able to migrate to an area between the retinal pigment epithelial and photoreceptor layers, which would allow the injection of cells into non-affected neighboring region so as not to worsen any compromised retinal components. iNPCs did, however, continue to express NSC/NPC markers and not mature neural/retinal markers, suggesting that grafted-iNPCs remained phenotypically uncommitted progenitor cells and did not differentiate towards a retinal phenotype. 

Further investigations excitingly found that iNPC-treatment reduced levels of toxic undigested photoreceptor outer segments (POS), whose accumulation due to a deficit in phagocytosis in the RCS mice leads to the photoreceptor death associated with AMD. This suggested to the authors that the grafted-iNPCs restored POS phagocytosis to RCS rats and they subsequently found that iNPCs expressed phagocytosis-related genes and could phagocytose and degrade POS in vitro. They extended this finding in vivo, showing different stages of digested POS close to the grafted cells and engulfed membranous discs inside the cytoplasm of iNPCs.

Overall, iNPC injection appears to be a safe and effective long-term treatment for AMD in the RCS rat preclinical model, and holds great promise for the translation into a patient-specific treatment for the preservation of existing retinal structure and vision during the early stages of AMD in humans. The authors do note that iNPC treatment at later stages of degeneration, which represents a more clinical relevant stage, remains unstudied, although they hope that the restoration of phagocytosis by iNPCs will represent an important strategy towards treating loss if visual acuity.


  1. Mullen RJ and LaVail MM Inherited retinal dystrophy: primary defect in pigment epithelium determined with experimental rat chimeras. Science 1976;192:799-801.
  2. Wang S, Girman S, Lu B, et al. Long-term vision rescue by human neural progenitors in a rat model of photoreceptor degeneration. Investigative ophthalmology & visual science 2008;49:3201-3206.
  3. Gamm DM, Wang S, Lu B, et al. Protection of visual functions by human neural progenitors in a rat model of retinal disease. PLoS One 2007;2:e338.
  4. Sareen D, Gowing G, Sahabian A, et al. Human induced pluripotent stem cells are a novel source of neural progenitor cells (iNPCs) that migrate and integrate in the rodent spinal cord. J Comp Neurol 2014;522:2707-2728.
  5. Tsai Y, Lu B, Bakondi B, et al. Human iPSC-Derived Neural Progenitors Preserve Vision in an AMD-Like Model. Stem Cells 2015;33:2537-2549.