iPS Cell Therapy for Retinitis pigmentosa and ARMD treatment: The promise of iPS Cell-Derived RPE Transplantation for Vision Restoration
- sakai208
- Feb 25
- 7 min read
Updated: Apr 1
iPS Cell Therapy for Retinitis pigmentosa and ARMD treatment: The promise of iPS Cell-Derived RPE Transplantation for Vision Restoration
Vision loss due to retinal diseases can profoundly impact an individual's quality of life. For many years, conditions like age-related macular degeneration (ARMD) and inherited retinal dystrophies presented significant challenges, with limited effective treatment options. However, the advent of induced pluripotent stem cell (iPS cell) technology has ushered in a new era of regenerative medicine. iPS cell-derived retinal pigment epithelium (RPE) transplantation, a pioneering technique developed in Japan, offers a groundbreaking approach to restoring vision by regenerating damaged retinal cells (RPE cells). This innovative therapy provides renewed hope for patients with previously untreatable conditions, particularly atrophic ARMD and retinitis pigmentosa, among other inherited retinal diseases.
Understanding RPE Dysfunction: The Target of iPS Cell Therapy
The retinal pigment epithelium (RPE) is a crucial layer of cells located between the photoreceptor cells (rods and cones) and the choroid (a layer of blood vessels) in the retina. The RPE plays a vital role in maintaining the health and function of the photoreceptors, providing essential nutrients, removing waste products, and absorbing stray light. Dysfunction or degeneration of the RPE cells can lead to various retinal diseases, collectively termed "RPE dysfunction syndrome." [1]
RPE Dysfunction and Related Diseases
Age-related macular degeneration (ARMD): ARMD, particularly the atrophic or "dry" form, is a leading cause of vision loss in older adults. In ARMD, the RPE cells gradually deteriorate, leading to the accumulation of drusen (yellow deposits) and the atrophy of the macula, the central part of the retina responsible for sharp, detailed vision.
Retinitis pigmentosa (RP): RP is a group of inherited retinal dystrophies that cause progressive degeneration of the photoreceptors and RPE. This degeneration typically begins with the loss of rod cells, leading to night blindness and peripheral vision loss, followed by the involvement of cone cells, resulting in decreased central vision and color vision.
Other inherited retinal dystrophies: A variety of other genetic conditions, such as Stargardt disease, Best disease, and choroideremia, can also affect the RPE and lead to vision loss.
iPS cell-derived RPE transplantation offers a promising therapeutic strategy by replacing the damaged or dysfunctional RPE cells with healthy, functional cells, potentially slowing down or even reversing the progression of these debilitating diseases.
The Promise of iPS Cell Technology in Retinal Regeneration
iPS cells are generated by reprogramming adult cells, such as skin or blood cells, back into a pluripotent state, meaning they have the ability to differentiate into any cell type in the body. This technology overcomes the ethical concerns associated with embryonic stem cells and provides a readily available source of cells for transplantation.
Advantages of iPS Cell-Derived RPE Transplantation
Cellular replacement: iPS cells can be differentiated into healthy RPE cells to replace damaged cells, potentially restoring the function of the retina.
Treatment for untreatable conditions: iPS cell therapy offers hope for diseases like atrophic ARMD and RP, where traditional treatments have limited effectiveness.
Clinical Research Advancements by the Kobe Team: A Journey of Innovation
Our team in Kobe has been at the forefront of iPS cell-derived RPE transplantation research, pioneering its development and conducting a series of clinical studies to evaluate its safety and efficacy. These studies have provided valuable insights into the potential of this therapy and paved the way for future clinical applications.
World's First iPS Cell-Derived RPE Sheet Transplantation (2014) [2]
In 2014, we achieved a significant milestone by performing the world's first iPS cell-derived RPE transplantation in a patient with advanced atrophic ARMD. This groundbreaking study involved transplanting autologous iPS cell-derived RPE cells (derived from the patient's own cells) in the form of a sheet into the affected area of the retina.
Key Findings:
The transplanted RPE cells survived and integrated into the retina.
There were no serious adverse events related to the transplantation.
The patient experienced stabilization of vision, and the need for anti-VEGF intravitreal injections, a standard treatment for wet ARMD, was reduced.
This initial study demonstrated the feasibility and safety of iPS cell-derived RPE transplantation, providing proof of concept for its potential to treat ARMD.
iPS Cell-Derived RPE Suspension Transplantation (2017, 2021) [3][4]
Building on the success of the first study, we conducted further clinical trials to refine the transplantation technique and expand its application. These studies involved transplanting allogeneic iPS cell-derived RPE cells (derived from donor cells) in the form of a suspension into patients with ARMD and RP.
Allogeneic Transplantation and HLA Matching:
To address the limitations of autologous transplantation, which requires a time-consuming and costly process to generate cells from each patient, we explored the use of allogeneic iPS cells.
To minimize the risk of immune rejection, we employed HLA (human leukocyte antigen) matching, selecting donor cells that closely matched the recipient's HLA type.
These studies demonstrated that allogeneic iPS cell-derived RPE cells could be safely transplanted with controlled immunosuppression.
Clinical Outcomes:
In ARMD patients, the transplanted RPE cells survived and showed signs of functional integration.
In patients with RPE65-associated inherited retinal degeneration (a specific form of RP), significant improvements in retinal sensitivity and visual function were observed.
These findings further supported the therapeutic potential of iPS cell-derived RPE transplantation for both ARMD and RP.
iPS Cell-Derived RPE Strip Transplantation (Latest Technology) [5]
To enhance the efficacy and safety of the transplantation procedure, we developed a novel method called RPE strip transplantation. This technique combines the advantages of sheet and suspension transplantation, offering a more controlled and minimally invasive approach.
Advantages of RPE Strip Transplantation:
Minimally invasive: The RPE cells are transplanted in the form of strips, reducing the size of the surgical incision and minimizing trauma to the retina.
Improved efficiency: The strips allow for more precise and efficient delivery of RPE cells to the target area.
Enhanced engraftment: The strips expand after subretinal transplantation to cover wider diseased areas.
Clinical Results:
Preliminary results from clinical studies using this technique have shown successful engraftment of the transplanted RPE cells.
A patient with ARMD demonstrated improvements in quality of vision.
These findings suggest that the RPE strip transplantation has the potential to further improve the outcomes of iPS cell-derived RPE therapy.
Future Prospects: Towards Broader Clinical Application and ARMD (Age-Related Macular Degeneration) Treatment and Retinitis Pigmentosa Treatment
The positive results from our clinical studies have paved the way for the translation of iPS cell-derived RPE transplantation into clinical practice. We are currently working towards obtaining regulatory approval to make this therapy more widely available to patients with ARMD and RP.
Advanced Medical Care Framework:
In Japan, the "Advanced Medical Care" framework allows for the provision of innovative therapies that have not yet been approved for general use but have shown promising clinical results.
We are actively pursuing this pathway to provide iPS cell-derived RPE transplantation to a larger number of patients who can benefit from this treatment.
Optimizing Patient Selection and Treatment Outcomes:
To ensure the success of iPS cell-derived RPE transplantation, careful patient selection is crucial.
Pre-operative precision diagnostics, including detailed imaging of the retina and genetic testing, are essential to identify patients who are most likely to benefit from the therapy.
We are developing standardized protocols for patient evaluation and treatment to optimize clinical outcomes.
Telemedicine Consultations:
To facilitate access to this innovative therapy for patients worldwide, we offer telemedicine consultations.
This allows patients and their physicians to consult with our team of experts remotely to discuss the suitability of iPS cell-derived RPE transplantation.
The Significance of iPS Cell-Derived RPE Transplantation for ARMD (Age-Related Macular Degeneration) Treatment
Age-related macular degeneration (ARMD) is a leading cause of irreversible vision loss in individuals aged 50 and older. The atrophic or "dry" form of ARMD, characterized by the gradual degeneration of the RPE and photoreceptors in the macula, accounts for the majority of ARMD cases. Currently, there are limited effective treatments for dry ARMD, highlighting the urgent need for new therapeutic approaches.
How iPS Cell-Derived RPE Transplantation Addresses the Challenges of ARMD Treatment:
RPE replacement: iPS cell-derived RPE transplantation directly addresses the underlying pathology of dry ARMD by replacing the damaged RPE cells with healthy, functional cells.
Slowing disease progression: By restoring RPE function, this therapy has the potential to slow down or halt the progression of ARMD and preserve central vision.
Improving quality of life: Preserving central vision can significantly improve the quality of life for ARMD patients, enabling them to maintain their independence and continue performing daily tasks.
iPS cell-derived RPE transplantation represents a paradigm shift in ARMD (age-related macular degeneration) treatment, offering a potential solution for a condition that has long been a major cause of visual disability.
The Potential of iPS Cell-Derived RPE Transplantation for Retinitis Pigmentosa Treatment
Retinitis pigmentosa (RP) is a group of inherited retinal dystrophies that affect the photoreceptor cells and RPE, leading to progressive vision loss. RP typically begins with night blindness and peripheral vision loss, eventually progressing to involve central vision. There is currently no definitive cure for RP, and treatment options are limited to managing symptoms.
How iPS Cell-Derived RPE Transplantation Offers Hope for Retinitis Pigmentosa Treatment:
Photoreceptor support: By replacing damaged RPE cells, iPS cell therapy can provide essential support to the remaining photoreceptors, potentially slowing down their degeneration.
Preserving visual function: This therapy has the potential to preserve or even improve visual function in RP patients, particularly in cases where RPE dysfunction plays a significant role.
iPS cell-derived RPE transplantation holds immense promise for retinitis pigmentosa treatment, offering a potential avenue to combat this devastating group of inherited retinal diseases.
Conclusion: Ushering in a New Era of Retinal Regeneration and Vision Restoration
iPS cell-derived RPE transplantation represents a transformative approach in combating vision loss due to retinal diseases like ARMD and RP. This innovative therapy holds the potential to restore vision, improve quality of life, and usher in a new era of retinal regeneration. We are committed to advancing this technology, conducting rigorous clinical research, and working towards making this treatment accessible to patients worldwide.
References
[1] Maeda T, Sugita S, Kurimoto Y, Takahashi M. Trends of stem cell therapies in age-related macular degeneration. J Clin Med. 2021;10(8):1785. https://www.mdpi.com/2077-0383/10/8/1785
[2] Mandai M, Watanabe A, Kurimoto Y, et al. Autologous induced stem-cell–derived retinal cells for macular degeneration. N Engl J Med. 2017;376(11):1038-1046. https://www.nejm.org/doi/full/10.1056/NEJMoa1608368
[3] Sugita S, Mandai M, Hirami Y, et al. HLA-matched allogeneic iPS cells-derived RPE transplantation for macular degeneration. J Clin Med. 2020;9(7):2217. https://www.mdpi.com/2077-0383/9/7/2217
[4] Maeda et al. In submission.
[5] Sakai D, Mandai M, Hirami Y, et al. Transplant of Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium Strips for Macular Degeneration and Retinitis Pigmentosa. Ophthalmol Sci. 2025 Article in Press. https://www.ophthalmologyscience.org/article/S2666-9145(25)00068-5/fulltext
This article was reviewed by
Dr. Daiki Sakai, MD
Author Biography
Dr. Daiki Sakai, MD is a Japanese board certified ophthalmologist and a phisician-scientist specialized in retinal diseases. He has published over 20 peer-reviewed ophthalmic papers. His main field of interests is clinical development of stem cell based retinal regenerative therapy, retinal imaging, genetic researchs on inherited retinal diseases.
