Age-related macular degeneration (AMD) is a common cause of central visual loss in the elderly. Retinal pigment epithelial (RPE) cell loss occurs early in the course of AMD and RPE cell transplantation holds promise to slow disease progression. We report that subretinal transplantation of RPE stem cell (RPESC)-derived RPE cells (RPESC-RPE) preserved vision in a rat model of RPE cell dysfunction. Importantly, the stage of differentiation that RPESC-RPE acquired prior to transplantation influenced the efficacy of vision rescue. Whereas cells at all stages of differentiation tested rescued photoreceptor layer morphology, an intermediate stage of RPESC-RPE differentiation obtained after 4 weeks of culture was more consistent at vision rescue than progeny that were differentiated for 2 weeks or 8 weeks of culture. Our results indicate that the developmental stage of RPESC-RPE significantly influences the efficacy of RPE cell replacement, which affects the therapeutic application of these cells for AMD.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5511099 | PMC |
| http://dx.doi.org/10.1016/j.stemcr.2017.05.016 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Pathology Findings and In-Life Correlates in the Nonclinical Development of Adeno-Associated Virus (AAV)-Based Retinal Gene Therapies.
Toxicol Pathol
December 2024
GEMpath, Inc., Longmont, Colorado, USA.
Adeno-associated virus (AAV)-based vectors are the most frequently used platform for retinal gene therapy. Initially explored for the treatment of loss-of-function mutations underpinning many inherited retinal diseases, AAV-based ocular gene therapies are increasingly used to transduce endogenous cells to produce therapeutic proteins, thus producing site-specific biofactories. Relatively invasive ocular routes of administration (ROA) mean prominent procedure-related in-life, and histopathological findings may be observed with some regularity.
View Article and Find Full Text PDFHow crosstalk between mitochondria, lysosomes, and other organelles can prevent or promote dry age-related macular degeneration.
Exp Eye Res
December 2024
Departments of Biochemistry and Ophthalmology, University of Washington, Seattle, WA, USA. Electronic address:
Organelles such as mitochondria, lysosomes, peroxisomes, and the endoplasmic reticulum form highly dynamic cellular networks and exchange information through sites of physical contact. While each organelle performs unique functions, this inter-organelle crosstalk helps maintain cell homeostasis. Age-related macular degeneration (AMD) is a devastating blinding disease strongly associated with mitochondrial dysfunction, oxidative stress, and decreased clearance of cellular debris in the retinal pigment epithelium (RPE).
View Article and Find Full Text PDFPreclinical study of novel human allogeneic adipose tissue-derived mesenchymal stem cell sheets toward a first-in-human clinical trial for myopic chorioretinal atrophy.
Stem Cell Res Ther
December 2024
Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan.
Background: Mesenchymal stem cells may have neuroprotective and tissue regenerative capabilities and the potential to rescue retinal degeneration in chorioretinal diseases including myopic chorioretinal atrophy. Transplantation of human (allogeneic) adipose tissue-derived mesenchymal stem cell (adMSC) suspensions has been clinically conducted to treat retinal degenerative diseases. However, serious side effects including proliferative vitreoretinopathy and epiretinal membrane formation have been reported.
View Article and Find Full Text PDFExtracellular Mitochondria Exacerbate Retinal Pigment Epithelium Degeneration in Diabetic Retinopathy.
Diabetes
December 2024
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Advances in fundus imaging are revealing disruptions in the neurovascular unit in diabetic retinopathy (DR). In the era of anti-VEGF treatment, a thorough characterization of neurodegeneration is imperative until DR patients are sufficiently cured. Here we demonstrate that extracellular mitochondria exacerbate retinal pigment epithelium (RPE) degeneration and inflammation in DR.
View Article and Find Full Text PDFEnzyme-Regulated Non-Thermal Fluctuations Enhance Ligand Diffusion and Receptor-Mediated Endocytosis.
bioRxiv
December 2024
Laboratory of Soft and Living Materials, Department of Physics, Indian Institute of Technology Gandhinagar, Palaj, Gandhinagar, Gujarat - 382055, India.
Active enzymes during catalyzing chemical reactions, have been found to generate significant mechanical fluctuations, which can influence the dynamics of their surroundings. These phenomena open new avenues for controlling mass transport in complex and dynamically inhomogeneous environments through localized chemical reactions. To explore this potential, we studied the uptake of transferrin molecules in retinal pigment epithelium (RPE) cells via clathrin-mediated endocytosis.
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!