Despite the progress of modern medicine in the last decades, millions of people diagnosed with retinal dystrophies (RDs), such as retinitis pigmentosa, or age-related diseases, such as age-related macular degeneration, are suffering from severe visual impairment or even legal blindness. On the one hand, the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) and the progress of three-dimensional (3D) retinal organoids (ROs) technology provide a great opportunity to study, understand, and even treat retinal diseases. On the other hand, research advances in the field of electronic retinal prosthesis using inorganic photovoltaic polymers and the emergence of organic semiconductors represent an encouraging therapeutical strategy to restore vision to patients at the late onset of the disease. This review will provide an overview of the latest advancement in both fields. We first describe the retina and the photoreceptors, briefly mention the most used RD animal models, then focus on the latest RO differentiation protocols, carry out an overview of the current technology on inorganic and organic retinal prostheses to restore vision, and finally summarize the potential utility and applications of ROs.
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http://dx.doi.org/10.3390/ijms23062922 | DOI Listing |
Exp Eye Res
January 2025
Institutes of Biology and Medical Sciences, Soochow University, Suzhou, 215000, China; Key Laboratory of Geriatric Diseases and Immunology, Ministry of Education, Institutes of Biology and Medical Sciences, Suzhou Medical College of Soochow University, Suzhou, 215123, China. Electronic address:
Due to its unique physiological structure and functions, the eye has received considerable attention in the field of adeno-associated virus (AAV) gene therapy. Inherited retinal degenerative diseases, which arise from pathogenic mutations in mRNA transcripts expressed in the eye's photoreceptor cells or retinal pigment epithelium (RPE), are the most common cause of vision loss. However, current retinal gene therapy mostly involves subretinal injection of therapeutic genes, which treats a limited area, entails retinal detachment, and requires sophisticated techniques.
View Article and Find Full Text PDFCommun Med (Lond)
January 2025
Department of Human Genetics, Research Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, The Netherlands.
Background: Stargardt disease type 1 (STGD1) is a progressive retinal disorder caused by bi-allelic variants in the ABCA4 gene. A recurrent variant at the exon-intron junction of exon 6, c.768G>T, causes a 35-nt elongation of exon 6 that leads to premature termination of protein synthesis.
View Article and Find Full Text PDFStem Cell Reports
January 2025
Research Center, Kobe City Eye Hospital, Kobe, Hyogo 650-0047, Japan; Research Organization of Science and Technology, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan; Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo 650-0047, Japan. Electronic address:
We have previously shown that the transplantation of stem cell-derived retinal organoid (RO) sheets into animal models of end-stage retinal degeneration can lead to host-graft synaptic connectivity and restoration of vision, which was further improved using genome-edited Islet1 ROs (gROs) with a reduced number of ON-bipolar cells. However, the details of visual function restoration using this regenerative therapeutic approach have not yet been characterized. Here, we evaluated the electrophysiological properties of end-stage rd1 retinas after transplantation (TP-rd1) and compared them with those of wild-type (WT) retinas using multi-electrode arrays.
View Article and Find Full Text PDFJ Transl Med
January 2025
Department of Ophthalmology, Renmin Hospital of Wuhan University, Jiefang Road, Wuhan, Hubei, 430060, China.
Diabetic retinopathy is a major ocular complication of diabetes, characterized by progressive retinal microvascular damage and significant visual impairment in working-age adults. Traditional bulk RNA sequencing offers overall gene expression profiles but does not account for cellular heterogeneity. Single-cell RNA sequencing overcomes this limitation by providing transcriptomic data at the individual cell level and distinguishing novel cell subtypes, developmental trajectories, and intercellular communications.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Ophthalmology, Leiden University Medical Center (LUMC), Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
Viral vector delivery of gene therapy represents a promising approach for the treatment of numerous retinal diseases. Adeno-associated viral vectors (AAV) constitute the primary gene delivery platform; however, their limited cargo capacity restricts the delivery of several clinically relevant retinal genes. In this study, we explore the feasibility of employing high-capacity adenoviral vectors (HC-AdVs) as alternative delivery vehicles, which, with a capacity of up to 36 kb, can potentially accommodate all known retinal gene coding sequences.
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