Background Aims: Retinal degeneration (RD) is an inherited eye disease characterized by irreversible photoreceptor loss. Conventionally, the activation of the resident microglia is secondary to the disease. Stem cell-based therapy has recently made rapid progress in treating RD. Although it has been demonstrated that the effect of stem cell therapy may include immunomodulation, the specific mechanisms have not been clarified.
Methods: Immunocytochemistry, terminal deoxynucleotidyl transferase UTP nick end labelling (TUNEL) assay and Western blot were used to analyze the microglia activation and photoreceptor apoptosis in the retina of rd1 mice. GFP-C17.2 neural stem cells (NSCs) were transplanted into the subretinal space to study the immunomodulatory and neuroprotective effects. The transwell co-culture of BV2 cells with GFP-C17.2 was performed to study the proliferation, apoptosis and secretion levels of inflammatory factors. Real time-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) were performed to explore the gene and protein level of factors secreted by NSCs and microglia.
Results: TUNEL-positive cells were primarily distributed in the inner nuclear layer (INL) of rd1 mice on P8d, appeared in the outer nuclear layer (ONL) on P10d and peaked on P14d. Meanwhile, microglia migrated to the ONL and reached the maximum level, accompanied by the changes in the levels of fractalkine and its unique receptor CX3CR1 protein. After transplantation of NSCs on P7d into the subretinal space of rd1 mice, the activated microglia were inhibited and the degeneration of ONL was delayed. In addition, microglia activation was suppressed by co-cultured NSCs in vitro. The gene and protein level of tissue inhibitor of metalloproteinase (TIMP1) in NSCs was elevated, whereas that of matrix metalloproteinase (MMP9) in BV2 microglia was markedly suppressed in this co-culture system.
Conclusions: Transplanted NSCs in the retina exerted immunomodulatory effects on microglia, thus delaying the degeneration of photoreceptors.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.jcyt.2016.03.001 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A Penetrable AAV2 Capsid Variant for Efficient Intravitreal Gene Delivery to the Retina.
Invest Ophthalmol Vis Sci
January 2025
Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Purpose: This study aimed to identify a novel recombinant adeno-associated virus (rAAV) capsid variant that can widely transfect the deep retina through intravitreal injection and to assess their effectiveness and safety in gene delivery.
Methods: By adopting the sequences of various cell-penetrating peptides and inserting them into the capsid modification region of AAV2, we generated several novel variants. The green fluorescent protein (GFP)-carrying variants were screened following intravitreal injection.
Subretinal microglia support donor photoreceptor survival in rd1 mice.
Stem Cell Res Ther
November 2024
Department of Ophthalmology, West China Hospital, Sichuan University, Cheng Du, Sichuan, China.
Purpose: To investigate the potential relationship between subretinal microglia and transplanted donor photoreceptors.
Methods: Photoreceptor precursors were transplanted into wild-type mice and rd1 mice by trans-scleral injection. Immunohistochemistry was employed to detect microglia and macrophages.
Multi-Characteristic Opsin Therapy to Functionalize Retina, Attenuate Retinal Degeneration, and Restore Vision in Mouse Models of Retinitis Pigmentosa.
Transl Vis Sci Technol
October 2024
Nanoscope Technologies LLC, Bedford, TX, USA.
Article Synopsis
- The study evaluated the impact of a viral vector-delivered multi-characteristic opsin (MCO-010) on vision in two mouse models of retinitis pigmentosa (rp1 and rp10), focusing on both structural and functional outcomes.
- MCO-010 was injected into the eyes of the mice, resulting in successful transduction of about 80% of bipolar cells without affecting retinal thickness, while control mice showed thinning.
- The treatment improved behavior and visual response in the mice without causing toxicity under challenging conditions, suggesting it could help slow retinal degeneration.
Host-Graft Synapses Form Functional Microstructures and Shape the Host Light Responses After Stem Cell-Derived Retinal Sheet Transplantation.
Invest Ophthalmol Vis Sci
October 2024
RIKEN Center for Biosystems Dynamics Research, Laboratory for Retinal Regeneration, Minato-jima, Chuo-ku, Kobe, Hyogo, Japan.
Purpose: Retinitis pigmentosa represents a leading cause of blindness in developed countries, yet effective treatments for the disease remain unestablished. Previous studies have demonstrated the potential of stem cell-derived retinal organoid (SC-RO) sheet transplantation to form host-graft synapses and to improve light responsiveness in animal models of retinal degeneration. However, the detailed microstructures of these de novo synapses and their functional contribution have not been well elucidated.
View Article and Find Full Text PDFPhotoreceptor-targeted extracellular vesicles-mediated delivery of Cul7 siRNA for retinal degeneration therapy.
Theranostics
September 2024
Department of Clinical Laboratory, Jinhua Central Hospital, Teaching Hospital of Mathematical Medicine College, Zhejiang Normal University, Jinhua 321000, Zhejiang, China.
Photoreceptor loss is a primary pathological feature of retinal degeneration (RD) with limited treatment strategies. RNA interference (RNAi) has emerged as a promising method of gene therapy in regenerative medicine. However, the transfer of RNAi therapeutics to photoreceptors and the deficiency of effective therapeutic targets are still major challenges in the treatment of RD.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!