Synaptic repair and vision restoration in advanced degenerating eyes by transplantation of retinal progenitor cells

He, Xiangyu; Zhao, Chenyang; Xu, Haiwei; Chen, Kang; Bian, Baishijiao; Gong, Yu; Weng, Chuanhuang; Zeng, Yuxiao; Fu, Yan; Liu, Yong; Yin, Zhinan

doi:10.1016/j.stemcr.2021.06.002

Cited by 16 publications

(11 citation statements)

References 35 publications

(61 reference statements)

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“…Preclinical studies have shown that retinal precursor cells at the peak of rod genesis can differentiate into rod photoreceptors when transplanted and integrate into the degenerating retina to form synaptic connections and improve visual function [ 164 ]. Calcium imaging studies on mice transplanted with C-Kit+/SSEA1− (C-Kit+) RPCs derived from organoids have revealed exceptional results in the formation of functional synapses with host cells, potentially stabilizing progressive vision loss [ 165 ]. Overall, the advantages of using RPCs include the secretion of trophic factors to increase the likelihood of retinal survival and photoreceptor replacement [ 166 ].…”

Section: Stem Cell Therapymentioning

confidence: 99%

Retinitis Pigmentosa: Novel Therapeutic Targets and Drug Development

Kulbay

Toameh

et al. 2023

Pharmaceutics

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Retinitis pigmentosa (RP) is a heterogeneous group of hereditary diseases characterized by progressive degeneration of retinal photoreceptors leading to progressive visual decline. It is the most common type of inherited retinal dystrophy and has a high burden on both patients and society. This condition causes gradual loss of vision, with its typical manifestations including nyctalopia, concentric visual field loss, and ultimately bilateral central vision loss. It is one of the leading causes of visual disability and blindness in people under 60 years old and affects over 1.5 million people worldwide. There is currently no curative treatment for people with RP, and only a small group of patients with confirmed RPE65 mutations are eligible to receive the only gene therapy on the market: voretigene neparvovec. The current therapeutic armamentarium is limited to retinoids, vitamin A supplements, protection from sunlight, visual aids, and medical and surgical interventions to treat ophthalmic comorbidities, which only aim to slow down the progression of the disease. Considering such a limited therapeutic landscape, there is an urgent need for developing new and individualized therapeutic modalities targeting retinal degeneration. Although the heterogeneity of gene mutations involved in RP makes its target treatment development difficult, recent fundamental studies showed promising progress in elucidation of the photoreceptor degeneration mechanism. The discovery of novel molecule therapeutics that can selectively target specific receptors or specific pathways will serve as a solid foundation for advanced drug development. This article is a review of recent progress in novel treatment of RP focusing on preclinical stage fundamental research on molecular targets, which will serve as a starting point for advanced drug development. We will review the alterations in the molecular pathways involved in the development of RP, mainly those regarding endoplasmic reticulum (ER) stress and apoptotic pathways, maintenance of the redox balance, and genomic stability. We will then discuss the therapeutic approaches under development, such as gene and cell therapy, as well as the recent literature identifying novel potential drug targets for RP.

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Section: Stem Cell Therapymentioning

confidence: 99%

Retinitis Pigmentosa: Novel Therapeutic Targets and Drug Development

Kulbay

Toameh

et al. 2023

Pharmaceutics

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“…In the field of translational medicine, ROs have been widely used in cell replacement therapy approaches 68,84–90 . The grafted organoid‐derived cells or sheets can mature and form synaptic connections between the graft and host following transplantation, but the functionality of the transplant itself is difficult to attain 86,89–91 . More convincing and direct evidence is needed to demonstrate the efficacy of therapeutic strategies in human ROs 92 .…”

Section: Development Of Neural Organoidsmentioning

confidence: 99%

“…68,[84][85][86][87][88][89][90] The grafted organoid-derived cells or sheets can mature and form synaptic connections between the graft and host following transplantation, but the functionality of the transplant itself is difficult to attain. 86,[89][90][91] More convincing and direct evidence is needed to demonstrate the efficacy of therapeutic strategies in human ROs. 92 Moreover, ROs are also promising tools to evaluate the potential adverse effects of toxic compounds on human retinal development.…”

Section: Generation and Characterization Of Retinal Organoidsmentioning

confidence: 99%

Toward the next generation of vascularized human neural organoids

Gao

Zhao

et al. 2022

Medicinal Research Reviews

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Thanks to progress in the development of threedimensional (3D) culture technologies, human central nervous system (CNS) development and diseases have been gradually deciphered by using organoids derived from human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs). Selforganized neural organoids (NOs) have been used to mimic morphogenesis and functions of specific organs in vitro. Many NOs have been reproduced in vitro, such as those mimicking the human brain, retina, and spinal cord. However, NOs fail to capitulate to the maturation and complexity of in vivo neural tissues. The persistent issues with current NO cultivation protocols are inadequate oxygen supply and nutrient diffusion due to the absence of vascular networks.In vivo, the developing CNS is interpenetrated by vasculature that not only supplies oxygen and nutrients but also provides a structural template for neuronal growth.To address these deficiencies, recent studies have begun to couple NO culture with bioengineering techniques and methodologies, including genetic engineering, coculture, multidifferentiation, microfluidics and 3D bioprinting, and transplantation, which might promote NO maturation and create more functional NOs. These cutting-edge methods could generate an ever more reliable NO model in vitro for deciphering the codes of human CNS development, disease progression, and translational application. In this review, we

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“…Transplanted cells were observed to have migrated into the degenerating retina. The development of functional synapses was shown by IHC for presynaptic and postsynaptic markers and with 2-photon calcium recording of donor cells 131…”

Section: Post-transplantation Analysismentioning

confidence: 99%

The Prospects for Retinal Organoids in Treatment of Retinal Diseases

Xue

Lin

Chen

et al. 2022

Asia-Pacific Journal of Ophthalmology

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Retinal degeneration (RD) is a significant cause of incurable blindness worldwide. Photoreceptors and retinal pigmented epithelium are irreversibly damaged in advanced RD. Functional replacement of photoreceptors and/or retinal pigmented epithelium cells is a promising approach to restoring vision. This paper reviews the current status and explores future prospects of the transplantation therapy provided by pluripotent stem cell-derived retinal organoids (ROs). This review summarizes the status of rodent RD disease models and discusses RO culture and analytical tools to evaluate RO quality and function. Finally, we review and discuss the studies in which ROderived cells or sheets were transplanted. In conclusion, methods to derive ROs from pluripotent stem cells have significantly improved and become more efficient in recent years. Meanwhile, more novel technologies are applied to characterize and validate RO quality. However, opportunity remains to optimize tissue differentiation protocols and achieve better RO reproducibility. In order to screen high-quality ROs for downstream applications, approaches such as noninvasive and label-free imaging and electrophysiological functional testing are promising and worth further investigation. Lastly, transplanted RO-derived tissues have allowed improvements in visual function in several RD models, showing promises for clinical applications in the future.

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Synaptic repair and vision restoration in advanced degenerating eyes by transplantation of retinal progenitor cells

Cited by 16 publications

References 35 publications

Retinitis Pigmentosa: Novel Therapeutic Targets and Drug Development

Retinitis Pigmentosa: Novel Therapeutic Targets and Drug Development

Toward the next generation of vascularized human neural organoids

The Prospects for Retinal Organoids in Treatment of Retinal Diseases

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