We investigated the role of methionine sulfoxide reductases (Msrs) in oxidant-stress-induced cell death in retinal pigmented epithelial (RPE) cells. In RPE cells exposed to varying doses of H(2)O(2), gene expression of MsrA and hCBS-1 (the human analog of MsrB2) increased in a dose-dependent and time-dependent manner with maximal increase with 150 microM H(2)O(2) in 24h. H(2)O(2) treatment resulted in the generation of reactive oxygen species and activation of caspase 3. Confocal microscopic and protein analysis showed an increase in MsrA expression in cytosol and mitochondria. Silencing of MsrA resulted in caspase 3 induction and accentuated cell death from H(2)O(2). Focal, strong immunoreactivity for MsrA was observed in sub-RPE macular drusen from patients with age-related macular degeneration. In summary, our data show that MsrA and hCBS-1 are up-regulated in oxidative stress to counteract injury to RPE.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbrc.2005.06.081 | 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 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 PDFProductive infection of the retinal pigment epithelium by SARS-CoV-2: Initial effects and consideration of long-term consequences.
PNAS Nexus
December 2024
Department of Ophthalmology and Stein Eye Institute, University of California, Los Angeles, CA 90095, USA.
As the SARS-CoV-2 coronavirus continues to evolve and infect the global population, many individuals are likely to suffer from post-acute sequelae of SARS-CoV-2 infection (PASC). Manifestations of PASC include vision symptoms, but little is known about the ability of SARS-CoV-2 to infect and impact the retinal cells. Here, we demonstrate that SARS-CoV-2 can infect and perturb the retinal pigment epithelium (RPE) in vivo, after intranasal inoculation of a transgenic mouse model of SARS-CoV-2 infection, and in cell culture.
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!