What Is Retinal Degeneration?
Retinal degeneration is a major cause of vision loss, and stem cell therapy has been intensively studied to repair and regenerate damaged retinal cells. Various types of stem cells have been studied in clinical and preclinical trials to understand their effectiveness in correcting retinal degeneration. Exosomes and paracrine factors obtained from MSCs and RPE (retinal pigment epithelium) cells derived from mesenchymal stem cells (MSCs), human embryonic stem cells (hESCs), retinal progenitor cells (RPCs), and induced pluripotent stem cells (iPSCs) are some of the stem cells used to treat retinal disorders.
The repair and regeneration of the damaged retinal tissue obtains the long-term effect of conventional therapy for retinal disorders. These therapies slow down the progression of the diseases. Furthermore, stem cell therapies have been tried to rejuvenate and repair the injured retina because they lack intrinsic regeneration capabilities. Numerous clinical and preclinical investigations have shown that the transplantation of stem cells and stem cell-derived components results in substantial improvements in the clinical state.
Both hereditary and non-genetic factors contribute to the formation of retinal degenerative illnesses, ultimately resulting in the loss of RPE cells and photoreceptor cells. Age-related macular degeneration (AMD) is a prevalent cause of visual loss that can be related to either choroidal neovascularization (wet AMD) or the destruction of RPE cells (dry AMD). Anti-VEGF therapy is a treatment for wet AMD that can restore vision clinically.
Proliferative or late-stage diabetic retinopathy (DR) is a result of chronic hyperglycemia and is managed with anti-VEGF therapy to prevent further neovascularization. The prognosis for the condition has improved with these conventional medicines, but repeated administration is necessary to slow the disease's progression. Gene therapy is only appropriate for people with vision loss due to specific mutations.
What Are Stem Cells?
Stem cells are undifferentiated, immature cells with a complex structure. These cells can differentiate into diverse body cell types. Stem cells can settle in an appropriate environment and multiply, propagating their population or differentiating into new cell types and producing cell populations. They can heal tissue and recover function after an injury. Therefore, they can replace or fix damaged retinal cells. Due to their unique characteristics, stem cells are being studied as a potential treatment for numerous diseases.
What Are the Properties of Stem Cells?
The properties are,
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Proliferation: Stem cells can divide and grow over a longer period.
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Self-Renewal: The resulting cell continues to function as a stem cell, like the parent cell, following division.
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Differentiation: Unspecialized stem cells can develop into specialized cells. Internal and external factors play crucial roles in this process. Genetic material within the cell controls internal stimuli. External stimuli are controlled by environmental chemicals, physical contact with nearby cells, and chemical substances secreted by other cells.
How Are Stem Cells Used in Retinal Diseases?
The use of stem cells in ocular treatment has various benefits. A significant cost-saving factor is the small number of stem cells needed. The surgical technique is quite simple, and the imaging techniques currently employed in clinical practice make it simple to monitor the transplanted cells. The other eye might serve as a control.
Moreover, the immunological effects of the eye eliminate the need for long-term immunosuppressive therapy. Replacing degenerating retinal cells with healthy stem cells has improved visual function by promoting cell regeneration and the formation of new intercellular connections. Stem cells can differentiate into various cells within their surroundings, such as photoreceptors and retinal neuron cells.
Previous in vitro research has demonstrated that stem cells are highly compatible with retinas and are adaptable to amacrine, Müller, horizontal, glial, bipolar, and photoreceptor cells. ESCs, IPSCs, and MSCs (derived from bone marrow and adipose tissue) are employed in stem cell therapy for retinal disorders.
Embryonic Stem Cells (ESCs):
ESCs have been employed as a cell source to treat various degenerative disorders, including retinal degeneration, because of their significant proliferation and differentiation capacity. No tumor growth was observed after hESC-derived RPE cells were subretinally transplanted into a preclinical mouse model of AMD. Seven months after the injection, the transplanted cells were still visible at the injection site, and some of the injected cells developed an RPE monolayer on top of the resident layer.
Induced Pluripotent Stem Cells (IPSCs):
Transplanting ESC-derived RPE cells necessitates local or systemic immunosuppression, even if the cells were functional and the patient's visual acuity improved. Recently, iPSCs have been used to treat a variety of illnesses. Mandai et al. revealed intriguing results from clinical trials, including transplanting RPE cells produced from iPSCs. The autologous transplantation of RPE cells made from iPSCs was well tolerated in a patient with advanced neovascular AMD despite the transplanted cell layer remaining intact, and there was no change in visual acuity after a year. Based on a four-year follow-up, the transplanted cells maintained the photoreceptors, and the patient's visual acuity remained steady without anti-VEGF medication.
Mesenchymal Stem Cells (MSCs):
Several preclinical and clinical studies were conducted with mesenchymal stem cells (MSCs) and their related substances to cure eye diseases. Sung et al. discovered that subtenon transplantation of human placenta-derived MSCs (PD-MSCs) was harmless and did not cause any negative inflammatory or proliferative side effects in a Phase I clinical trial involving four Asian patients with traumatic optic neuropathy.
Along with improving visual acuity, PD-MSCs exerted a protective impact on RGCs and restored the expression of GFAP and Tuj1. Intravitreal autologous BM-MSC transplantation was performed in a non-randomized phase I clinical trial involving 14 patients with RP. The improvement in visual function was evaluated at one, three, and seven years post-transplantation. All patients showed an increase in intraocular pressure (IOP) soon after transplantation, and within 24 hours, their IOP reverted to baseline.
Conclusion
However, there needs to be more understanding of the delivery route, method of result evaluation, long-term effects of stem cell transplantations, and source of stem cells. Donor-based differences in the functionality of RPE cells produced from iPSCs should be considered before transplantation. It is important to take into account age and niche-related changes in MSC function in clinical settings.
