Inherited retinal diseases (IRDs) are a large group of genetically and clinically diverse blinding eye conditions that result in progressive and irreversible photoreceptor degeneration and vision loss. To date, no cures have been found, although strides toward treatments for specific IRDs have been made in recent years. To accelerate treatment discovery, retinal organoids provide an ideal human IRD model. This review aims to give background on the development and importance of retinal organoids for the human-based study of the retina and human retinogenesis and retinal pathologies. From there, we explore retinal pathologies in the context of IRDs and the current landscape of IRD treatment discovery. We discuss the usefulness of retinal organoids in this context (as a patient-derived cell model for IRDs) to precisely understand the pathogenesis and potential mechanisms behind a specific IRD-causing variant of interest. Finally, we discuss the importance and promise of retinal organoids in treatment discovery for IRDs, now and in the future.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11203130 | PMC |
| http://dx.doi.org/10.3390/genes15060705 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Understanding retinal tau pathology through functional 2D and 3D iPSC-derived in vitro retinal models.
Acta Neuropathol Commun
January 2025
Department of Physiology and Pharmacology, Sapienza University of Rome, 00185, Rome, Italy.
The generation of retinal models from human induced pluripotent stem cells holds significant potential for advancing our understanding of retinal development, neurodegeneration, and the in vitro modeling of neurodegenerative disorders. The retina, as an accessible part of the central nervous system, offers a unique window into these processes, making it invaluable for both study and early diagnosis. This study investigates the impact of the Frontotemporal Dementia-linked IVS 10 + 16 MAPT mutation on retinal development and function using 2D and 3D retinal models derived from human induced pluripotent stem cells.
View Article and Find Full Text PDFModelling neurodegeneration and inflammation in early diabetic retinopathy using 3D human retinal organoids.
In Vitro Model
February 2024
iNOVA4Health, NOVA Medical School|Faculdade de Ciências Médicas, NMS|FCM, Universidade Nova de Lisboa, Rua Camara Pestana, 6, Lisbon, Portugal.
Purpose: Diabetic retinopathy (DR) is a complication of diabetes and a primary cause of visual impairment amongst working-age individuals. DR is a degenerative condition in which hyperglycaemia results in morphological and functional changes in certain retinal cells. Existing treatments mainly address the advanced stages of the disease, which involve vascular defects or neovascularization.
View Article and Find Full Text PDFScreening of a retinal-targeting Adeno-Associated Virus (AAV) via DNA shuffling.
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 PDFPreclinical assessment of splicing modulation therapy for ABCA4 variant c.768G>T in Stargardt disease.
Commun 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 PDFTransplantation of genome-edited retinal organoids restores some fundamental physiological functions coordinated with severely degenerated host retinas.
Stem 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 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!