scholarly journals Transplanted embryonic retinal stem cells have the potential to repair the injured retina in mice

2021 ◽  
Author(s):  
Xia Feng ◽  
Peng Chen ◽  
Xin Zhao ◽  
Jing Wang ◽  
Hong Wang

Abstract Background: Stem cell transplantation has been reported as one of the promising strategies to treat retinal degenerative diseases. But, the application and the role of retina stem cells (RSCs) in the treatment of patients with retinal degenerative diseases have not been fully revealed. This study aimed to investigate the potential role of transplantation of the embryo-derived RSCs into the vitreous cavity in repairing the damaged retina in mice.Methods: RSCs were isolated from Kunming mice E17 embryonic retina and ciliary body tissues, and labeled with 5-bromo-2’-deoxyuridin (BrdU). Retinal optic nerve crush injury was induced in left eyes in male Kunming mice by ring clamping the optic nerve. The 6th-generation of BrdU-labeled RSCs were transplanted into the damaged retina by the intravitreal injection, and saline injected eyes were used as the control. Hematoxylin and eosin histological staining, and BrdU, Nestin and Pax6 immunostaining were performed. Electroretinogram (ERG) was used for assessing the electrical activity of the retina.Results: Embryo-derived RSCs were identified by the positive stains of Pax6 and Nestin. BrdU incorporation was detected in the majority of RSCs. The damaged retina showed cellular nuclear disintegration and fragmentation in the retinal tissue which progressed over the periods of clamping time, and decreased amplitudes of a and b waves in ERG. In the damaged retina with RSCs transplantation, the positive staining for BrdU, Pax6 and Nestin were revealed on the retinal surface. Notably, RSCs migrated into the retinal ganglion cell layer and inner nuclear. Transplanted RSCs significantly elevated the amplitudes of a waves in retina injured eyes.Conclusions: Embryonic RSCs have similar characteristics to neural stem cells. Transplantation of RSCs by intravitreal injection would be able to repair the damaged retina.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xia Feng ◽  
Peng Chen ◽  
Xin Zhao ◽  
Jing Wang ◽  
Hong Wang

Abstract Background Stem cell transplantation has been reported as one of the promising strategies to treat retinal degenerative diseases. But, the application and the role of retina stem cells (RSCs) in the treatment of patients with retinal degenerative diseases have not been fully revealed. This study aimed to investigate the potential role of transplantation of the embryo-derived RSCs into the vitreous cavity in repairing the damaged retina in mice. Methods RSCs were isolated from Kunming mice E17 embryonic retina and ciliary body tissues, and labeled with 5-bromo-2’-deoxyuridin (BrdU). Retinal optic nerve crush injury was induced in left eyes in male Kunming mice by ring clamping the optic nerve. The 6th -generation of BrdU-labeled RSCs were transplanted into the damaged retina by the intravitreal injection, and saline injected eyes were used as the control. Hematoxylin and eosin histological staining, and BrdU, Nestin and Pax6 immunostaining were performed. Electroretinogram (ERG) was used for assessing the electrical activity of the retina. Results Embryo-derived RSCs were identified by the positive stains of Pax6 and Nestin. BrdU incorporation was detected in the majority of RSCs. The damaged retina showed cellular nuclear disintegration and fragmentation in the retinal tissue which progressed over the periods of clamping time, and decreased amplitudes of a and b waves in ERG. In the damaged retina with RSCs transplantation, the positive staining for BrdU, Pax6 and Nestin were revealed on the retinal surface. Notably, RSCs migrated into the retinal ganglion cell layer and inner nuclear. Transplanted RSCs significantly elevated the amplitudes of a waves in retina injured eyes. Conclusions Embryonic RSCs have similar characteristics to neural stem cells. Transplantation of RSCs by intravitreal injection would be able to repair the damaged retina.


2020 ◽  
Author(s):  
Xia Feng ◽  
Peng Chen ◽  
Xin Zhao ◽  
Jing Wang ◽  
Hong Wang

Abstract Background: Stem cell transplantation has been reported as one of the promising strategies to treat retinal degenerative diseases. But, the application and the role of retina stem cells (RSCs) in the treatment of patients with retinal degenerative diseases have not been fully revealed. This study aimed to investigate the potential role of transplantation of the embryo-derived RSCs into the vitreous cavity in repairing the damaged retina in mice. Methods: RSCs were isolated from Kunming mice E17 embryonic retina and ciliary body tissues, and labeled with 5-bromo-2’-deoxyuridin (BrdU). Retinal injury was induced in left eyes in male Kunming mice by ring clamping the optic nerve. The 6th-generation of BrdU-labeled RSCs were transplanted into the damaged retina by the intravitreal injection, and saline injected eyes were used as the control. Hematoxylin and eosin histological staining, and BrdU, Nestin and Pax6 immunostaining were performed. Electroretinogram (ERG) was used for assessing the electrical activity of the retina. Results: Embryo-derived RSCs were identified by the positive stains of Pax6 and Nestin. BrdU incorporation was detected in the majority of RSCs. The damaged retina showed cellular nuclear disintegration and fragmentation in the retinal tissue which progressed over the periods of clamping time, and decreased amplitudes of a and b waves in ERG. In the damaged retina with RSCs transplantation, the positive staining for BrdU, Pax6 and Nestin were revealed on the retinal surface. Notably, a small amount of RSCs migrated into the retinal ganglion cell layer and inner nuclear. Transplanted RSCs significantly elevated the amplitudes of a waves in retina injured eyes. Conclusions: Embryonic RSCs have similar characteristics to neural stem cells. Transplantation of RSCs by intravitreal injection would be able to repair the damaged retina.


2020 ◽  
Author(s):  
Xia Feng ◽  
Peng Chen ◽  
Xin Zhao ◽  
Jing Wang ◽  
Hong Wang

Abstract Background: Stem cell transplantation has been reported as one of the promising strategies to treat retinal degenerative diseases, but this field is so complicated and still relatively new. This study investigated the potential role of transplantation of the embryo-derived retina stem cells (RSCs) into the vitreous cavity in repairing the damaged retina in mice.Methods: RSCs were isolated from Kunming mice E17 embryonic retina and ciliary body tissues. RSCs were cultured, differentiated, and labeled with 5-bromo-2’-deoxyuridin (BrdU). Retinal injury was induced in left eyes in male Kunming mice by ring clamping of the optic nerve. The 6th-generation of BrdU-labeled RSCs were transplanted into the damaged retina by the intravitreal injection, and saline injected eyes were used as the control. Hematoxylin and eosin histological staining, and BrdU, Nestin and Pax6 immunostaining were performed.Results: Embryo-derived RSCs were identified by the positive stains of Pax6 and Nestin. BrdU incorporation was detected in most of RSCs. The damaged retina showed diffuse edema, disordered and loose-arranged morphological changes in all retinal layers. In the damaged retina with RSCs transplantation, the positive staining for BrdU, Pax6 and Nestin were revealed on the retinal surface. Notably, a small amount of RSCs migrated into the retinal ganglion cell layer and inner nuclear.Conclusions: Embryonic RSCs have similar characteristics to neural stem cells. Transplantation of RSCs by intravitreal injection would be able to repair the damaged retina.


2020 ◽  
Vol 6 (1) ◽  
pp. 195-213
Author(s):  
Philip R. Williams ◽  
Larry I. Benowitz ◽  
Jeffrey L. Goldberg ◽  
Zhigang He

The damage or loss of retinal ganglion cells (RGCs) and their axons accounts for the visual functional defects observed after traumatic injury, in degenerative diseases such as glaucoma, or in compressive optic neuropathies such as from optic glioma. By using optic nerve crush injury models, recent studies have revealed the cellular and molecular logic behind the regenerative failure of injured RGC axons in adult mammals and suggested several strategies with translational potential. This review summarizes these findings and discusses challenges for developing clinically applicable neural repair strategies.


2020 ◽  
Vol 51 (1) ◽  
pp. 89-97
Author(s):  
Fen Tang ◽  
Fan Xu ◽  
Ling Cui ◽  
Wei Huang ◽  
Li Jiang ◽  
...  

Author(s):  
Deepthi Rajendran Nair ◽  
Biju Thomas

Background: The main cause of progressive vision impairment in retinal degenerative diseases is the dysfunction of photoreceptors and the underlying retinal pigment epithelial cells. The inadequate regenerative capacity of the neural retina and lack of established therapeutic options demand the development of clinical grade protocols to halt degenerative process in the eye or to replace the damaged cells by using stem cell derived products. Recently, stem cell-based regenerative therapies are at the forefront of clinical investigations for retinal dystrophies. Objective: This article will review different stem cell-based therapies currently employed for retinal degenerative diseases, recent clinical trials, and major challenges in the translation of these therapies from bench to bedside. Methodology: A systematic literature review was carried out to identify potentially relevant articles published in MEDLINE/PubMed, Embase, ClinicalTrials.gov, Drugs@FDA, European Medicines Agency, World Health Organization International Clinical Trials Registry Platform and CENTRAL Result: Transplantation of healthy cells to replace the damaged cells in the outer retina is a clinically relevant concept because the inner retina that communicates with the visual areas of the brain remains functional even after the photoreceptors are completely lost. Different methods have been established for the differentiation of pluripotent stem cells into different retinal cell types that can be used for therapies. Factors released from transplanted somatic stem cells showed trophic support and photoreceptor rescue during early stages of the disease. Several preclinical and phase I/II clinical studies using terminally differentiated photoreceptor/ retinal pigment epithelial cells derived from pluripotent stem cells have shown proof of concept for visual restoration in Age-related macular degeneration (AMD), Stargardt disease and Retinitis pigmentosa (RP). Conclusion: Cell replacement therapy has great potential for vision restoration. The results obtained from the initial clinical trials are encouraging and indicates its therapeutic benefits. The current status of the therapies suggests that there is a long way to go before these results can be applied to routine clinical practice. Input from the ongoing multicentre clinical trials will give a more refined idea for the future design of clinical- grade protocols to transplant GMP level HLA matched cells.


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