The aims of the present study were to investigate the effect of E50K optineurin (OPTN) mutation on RGC‑5 cells and to define the role of microRNA‑9 (miR‑9) in this system. Transfected RGC‑5 cells were used to evaluate the effects of E50K OPTN on the expression of miR‑9 and subsequent disruption of RGC‑5 cell apoptosis was analyzed using western blotting. The results showed that the expression of E50K OPTN was associated with a marked reduction in the levels of miR‑9 in the E50K OPTN‑transfected RGC‑5 cells. The E50K OPTN‑dependent reductions in miR‑9 led to increased expression of the transcriptional repressor, RE1‑silencing transcription factor and decreased the expression of brain‑derived neurotrophic factor. Thus, E50K OPTN may disrupt the expression of miR‑9, suggesting a potential mechanism by which E50K OPTN mutation may lead to RGC‑5 cell apoptosis.
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http://dx.doi.org/10.3892/mmr.2016.5810 | DOI Listing |
Inflammation
November 2024
Department of Ophthalmology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
OPTN (E50K) mutation is one of the significant pathogenic mutations in normal tension glaucoma (NTG). The molecular mechanism of NTG optic nerve injury is complex and diverse; its key mechanism is still unclear. The NLR family pyrin domain containing (NLRP3) inflammasome plays an essential role in the occurrence and development of inflammation.
View Article and Find Full Text PDFFluids Barriers CNS
November 2024
Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Glaucoma is a neurodegenerative disease that results in the degeneration of retinal ganglion cells (RGCs) and subsequent loss of vision. While RGCs are the primary cell type affected in glaucoma, neighboring cell types selectively modulate RGCs to maintain overall homeostasis. Among these neighboring cell types, astrocytes, microvascular endothelial cells (MVECs), and pericytes coordinate with neurons to form the neurovascular unit that provides a physical barrier to limit the passage of toxic materials from the blood into neural tissue.
View Article and Find Full Text PDFCell Death Differ
October 2024
Department of Immunology Discovery, Genentech, 1 DNA Way, South San Francisco, CA, USA.
Receptor-interacting protein 1 (RIP1, RIPK1) is a critical mediator of multiple signaling pathways that promote inflammatory responses and cell death. The kinase activity of RIP1 contributes to the pathogenesis of a number of inflammatory and neurodegenerative diseases. However, the role of RIP1 in retinopathies remains unclear.
View Article and Find Full Text PDFActa Neuropathol Commun
October 2024
Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
The ability to derive retinal ganglion cells (RGCs) from human pluripotent stem cells (hPSCs) has led to numerous advances in the field of retinal research, with great potential for the use of hPSC-derived RGCs for studies of human retinal development, in vitro disease modeling, drug discovery, as well as their potential use for cell replacement therapeutics. Of all these possibilities, the use of hPSC-derived RGCs as a human-relevant platform for in vitro disease modeling has received the greatest attention, due to the translational relevance as well as the immediacy with which results may be obtained compared to more complex applications like cell replacement. While several studies to date have focused upon the use of hPSC-derived RGCs with genetic variants associated with glaucoma or other optic neuropathies, many of these have largely described cellular phenotypes with only limited advancement into exploring dysfunctional cellular pathways as a consequence of the disease-associated gene variants.
View Article and Find Full Text PDFCurr Med Sci
April 2023
Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Objective: To explore the role of extracellular vesicles (EVs) in the pathogenesis of glaucoma caused by E50K mutation.
Methods: A photoreceptor cell line, RGC-5, was transfected with empty plasmids and plasmids expressing wild-type (WT) optineurin (OPTN) or E50K OPTN to investigate the effects of OPTN glaucoma as well as to identify the role of EVs in glaucoma pathology. The RGC-5 cells were also stimulated with glutamate, and their viability was evaluated using flow cytometry or CCK-8 assay.
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