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Restoring Vision with Human-Induced Pluripotent Stem Cells: A Revolution in Photoreceptor Regeneration

by | Sep 1, 2025 | Manuscripts | 0 comments

Sathishkumar S, B. Optom.

MSc. Integrative Biology and Physiology Student (iMOV Track), Sorbonne University, Paris, France

 
Vision impairment is a major global health issue, with conditions like Retinitis Pigmentosa (RP) causing progressive loss and leading to blindness. RP is characterised by the degeneration of photoreceptors, light-sensitive cells in the retina, including rods, which are responsible for vision in dim light conditions, and cones, which are crucial for colour perception and fine detail. This degeneration is caused by over 200 genetic mutations in more than 70 different genes, affecting millions worldwide.

Recent advancements in human-induced Pluripotent Stem Cell (hiPSC) research offer promising advancements for vision restoration by initiating the regeneration of photoreceptors. These breakthroughs highlight the potential of hiPSC-based therapies to revolutionise treatment strategies and improve the quality of life for individuals affected by RP. (1)

Stem Cell Therapy

Stem cell therapy has emerged as a promising approach for treating degenerative diseases, with hiPSCs representing a breakthrough. These cells are generated by re-programming adult cells, such as skin or blood cells, into a pluripotent state, allowing them to develop into any cell type, including retinal cells. (2)

The applications of hiPSCs are wide-ranging and include modelling retinal diseases to improve our understanding, testing drugs safely and efficiently, validating gene therapy strategies, and regenerating photoreceptors for transplantation. (3) A significant advancement in this field is the creation of retinal organoids, which are lab-grown mini-retinas that mimic the structure and function of the human retina. (4)

Figure 1: Procedure for Growing Retinal Organoid

This process involves several carefully monitored stages. First, adult cells are reprogrammed into hiPSCs. Next, during neural induction, these cells are guided to become retinal progenitor cells using specialised growth media. (4) The cells then undergo differentiation, forming early retinal layers. Over a maturation period of about 200 days, the organoids develop into structures resembling a natural retina, complete with rods and cones. (5)

In real-world applications, recent clinical studies have demonstrated the potential of hiPSC-based therapies. In one study, hiPSC-derived retinal sheets were transplanted into two patients with end-stage Retinitis Pigmentosa (RP). (6) However, further research is needed to enhance outcomes and ensure seamless integration of transplanted cells with the existing retina of the patient.

The functionality of retinal organoids is assessed using advanced techniques to ensure their readiness for clinical application. Patch clamp testing evaluates the electrical activity of photoreceptors, confirming their ability to respond to light, while multi-electrode arrays measure neuronal activity to ensure proper communication between retinal cells.

Conclusion

Although vision loss due to conditions like RP significantly impacts the quality of life, the promise offered by hiPSC technology presents a feasible strategy for regenerative treatment. However, considerable work is needed to optimise these therapies, and while promising, the translation of these advancements into effective, widely accessible clinical solutions remains a complex and multi-faceted challenge.

References

  1. Karagiannis P., Takahashi K., Saito M., Yoshida Y., Okita K., Watanabe A., Inoue H., Yamashita J. K., Todani M., Nakagawa M., Osawa M., Yashiro Y., Yamanaka S., and Osafune K., Induced pluripotent stem cells and their use in human models of disease and development, Physiological Reviews. (2019) 99, no. 1, 79–114, https://doi.org/10.1152/physrev.00039.2017, 2-s2.0-85055080136, 30328784.
  2. Wiley L. A., Burnight E. R., Songstad A. E., Drack A. V., Mullins R. F., Stone E. M., and Tucker B. A., Patient-specific induced pluripotent stem cells (iPSCs) for the study and treatment of retinal degenerative diseases, Progress in Retinal and Eye Research. (2015) 44, 15–35, https://doi.org/10.1016/j.preteyeres.2014.10.002, 2-s2.0-84916198284, 25448922.
  4. Jin Z.-B., Gao M.-L., Deng W.-L., Wu K. C., Sugita S., Mandai M., and Takahashi M., Stemming retinal regeneration with pluripotent stem cells, Progress in Retinal and Eye Research. (2019) 69, 38–56, https://doi.org/10.1016/j.preteyeres.2018.11.003, 2-s2.0-85056715932.
  5. Reichman S, Terray A, Slembrouck A, Nanteau C, Orieux G, Habeler W, Nandrot EF, Sahel JA, Monville C, Goureau O. From confluent human iPS cells to self-forming neural retina and retinal pigmented epithelium. Proceedings of the National Academy of Sciences. 2014 Jun 10;111(23):8518-23.
  6. Reichman S, Slembrouck A, Gagliardi G, Chaffiol A, Terray A, Nanteau C, Potey A, Belle M, Rabesandratana O, Duebel J, Orieux G. Generation of storable retinal organoids and retinal pigmented epithelium from adherent human iPS cells in xeno-free and feeder-free conditions. Stem cells. 2017 May 1;35(5):1176-88.
  7. Hirami Y, Mandai M, Sugita S, Maeda A, Maeda T, Yamamoto M, Uyama H, Yokota S, Fujihara M, Igeta M, Daimon T. Safety and stable survival of stem-cell-derived retinal organoid for 2 years in patients with retinitis pigmentosa. Cell Stem Cell. 2023 Dec 7;30(12):1585-96.

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