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Stem Cell Therapy for Retinal Degeneration: The Evidence to Date.

ABSTRACT: There is a rise in the number of people who have vision loss due to retinal diseases, and conventional therapies for treating retinal degeneration fail to repair and regenerate the damaged retina. Several studies in animal models and human trials have explored the use of stem cells to repair the retinal tissue to improve visual acuity. In addition to the treatment of age-related macular degeneration (AMD) and diabetic retinopathy (DR), stem cell therapies were used to treat genetic diseases such as retinitis pigmentosa (RP) and Stargardt's disease, characterized by gradual loss of photoreceptor cells in the retina. Transplantation of retinal pigment epithelial (RPE) cells derived from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have shown promising results in improving retinal function in various preclinical models of retinal degeneration and clinical studies without any severe side effects. Mesenchymal stem cells (MSCs) were utilized to treat optic neuropathy, RP, DR, and glaucoma with positive clinical outcomes. This review summarizes the preclinical and clinical evidence of stem cell therapy and current limitations in utilizing stem cells for retinal degeneration.

SUBMITTER: Sharma A

PROVIDER: S-EPMC8327474 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Stem Cell Therapy for Retinal Degeneration: The Evidence to Date.

Sharma Amit A Jaganathan Bithiah Grace BG

Biologics : targets & therapy 20210727

There is a rise in the number of people who have vision loss due to retinal diseases, and conventional therapies for treating retinal degeneration fail to repair and regenerate the damaged retina. Several studies in animal models and human trials have explored the use of stem cells to repair the retinal tissue to improve visual acuity. In addition to the treatment of age-related macular degeneration (AMD) and diabetic retinopathy (DR), stem cell therapies were used to treat genetic diseases such ...[more]

PMID: 34349498

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Project description:Adipose-derived stem cells (ASCs) have shown a strong protective effect on retinal degenerative diseases (RDD) after being transplanted into the subretinal space in an animal model. Recently, several clinical trials have been conducted to treat RDD with intravitreal transplantation of stem cells, including ASCs. However, the outcomes of the clinical trials were not satisfactory. To investigate if the transplantation site alters the outcome of stem cell-based therapy for RDD, we isolated rat ASCs (rASCs) and labeled them with green fluorescent protein. Autologous rASCs were grafted into the vitreous chamber or subretinal space in a rat RDD model induced by sodium iodate (SI). The electric response was recorded by ERG. The anatomic structure of the retina was observed in cryosections of rat eyes at posttransplantation weeks 1, 2, and 4. Neural retina apoptosis and epiretinal membrane- (ERM-) like structure formation were investigated by immunostaining. The intravitreal transplantation of rASCs resulted in an extinguished electric response, although the rosette formation and apoptosis of neural retina were reduced. However, the rASCs that grafted in the subretinal space protected the retina from the damage caused by SI, including a partial recovering of the electric response and a reduction in rosette formation. Intravitreally grafted rASCs formed a membrane, resulting in retina folding at the injection site. Müller cells, retinal pigment epithelial cells, and microglial cells migrated from the retina to the rASC-formed membrane and subsequently formed an ERM-like structure. Furthermore, vitreous fluid promoted rASC migration, and rASC-conditioned medium enhanced Müller cell migration as indicated by in vitro studies. These data suggested that the vitreous chamber is not a good transplantation site for ASC-based therapy for RDD and that a deliberate decision should be made before transplantation of stem cells into the vitreous chamber to treat RDD in clinical trials.

Project description:Retinal degenerative disorders (RDs) are the main cause of blindness without curable treatment. Our previous studies have demonstrated that human-induced pluripotent stem cells can differentiate into retinal organoids with all subtypes of retina, which provides huge promise for treating these diseases. Before these methods can be realized, RD animal models are required to evaluate the safety and efficacy of stem cell therapy and to develop the surgical tools and procedures for cell transplantation in patients. This study involved the development of a monkey model of RD with controllable lesion sites, which can be rapidly prepared for the study of preclinical stem cell therapy among other applications. Sodium nitroprusside (SNP) in three doses was delivered into the monkey eye by subretinal injection (SI), and normal saline was applied as control. Structural and functional changes of the retinas were evaluated via multimodal imaging techniques and multifocal electroretinography (mfERG) before and after the treatment. Histological examination was performed to identify the target layer of the affected retina. The health status of monkeys was monitored during the experiment. Well-defined lesions with various degrees of retinal degeneration were induced at the posterior pole of retina as early as 7 days after SNP SI. The damage of SNP was dose dependent. In general, 0.05 mM SNP caused mild structural changes in the retina; 0.1 mM SNP led to the loss of outer retinal layers, including the outer plexiform layer (OPL), outer nuclear layer (ONL), and retinal pigment epithelium (RPE); while 0.2 mM SNP impacted the entire layer of the retina and choroid. MfERG showed reduced amplitude in the damaged region. The structural and functional damages were not recovered at 7-month follow-up. A rapidly induced lesion site-controllable retinal degeneration monkey model was established by the subretinal administration of SNP, of which the optimal dose is 0.1 mM. This monkey model mimics the histological changes of advanced RDs and provides a valuable platform for preclinical assessment of stem cell therapy for RDs.

Dataset Information

Stem Cell Therapy for Retinal Degeneration: The Evidence to Date.

Publications

Stem Cell Therapy for Retinal Degeneration: The Evidence to Date.

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