Investigative ophthalmology & visual science
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Invest. Ophthalmol. Vis. Sci. · Oct 2020
Co-Expression of Mitochondrial Genes and ACE2 in Cornea Involved in COVID-19.
The coronavirus disease 2019 (COVID-19) pandemic severely challenges public health and necessitates the need for increasing our understanding of COVID-19 pathogenesis, especially host factors facilitating virus infection and propagation. The aim of this study was to investigate key factors for cellular susceptibility to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection in the ocular surface cells. ⋯ Our co-expression and protein interaction network analysis uncover that the mitochondrial function related genes in cornea contribute to the dissection of COVID-19 susceptibility and potential therapeutic interventions.
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Invest. Ophthalmol. Vis. Sci. · May 2020
Small Molecules Restore Bestrophin 1 Expression and Function of Both Dominant and Recessive Bestrophinopathies in Patient-Derived Retinal Pigment Epithelium.
Bestrophinopathies are a group of untreatable inherited retinal dystrophies caused by mutations in the retinal pigment epithelium (RPE) Cl- channel bestrophin 1. We tested whether sodium phenylbutyrate (4PBA) could rescue the function of mutant bestrophin 1 associated with autosomal dominant and recessive disease. We then sought analogues of 4PBA with increased potency and determined the mode of action for 4PBA and a lead compound 2-naphthoxyacetic acid (2-NOAA). Lastly, we tested if 4PBA and 2-NOAA could functionally rescue bestrophin 1 function in RPE generated from induced pluripotent stem cells (iPSC-RPEs) derived from patients with a dominant or recessive bestrophinopathy. ⋯ The restoration of bestrophin 1 function in patient-derived RPE confirms the US Food and Drug Administration-approved drug 4PBA as a promising therapeutic treatment for bestrophinopathies.
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Invest. Ophthalmol. Vis. Sci. · Nov 2019
Long Noncoding RNA PVT1 Silencing Prevents the Development of Uveal Melanoma by Impairing MicroRNA-17-3p-Dependent MDM2 Upregulation.
Uveal melanoma is a common primary intraocular malignancy accompanied by high mortality. Previous evidence has highlighted the implication of microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) in uveal melanoma. Accordingly, we further uncovered the possible role of lncRNA plasmacytoma variant translocation 1 gene (PVT1) and microRNA-17-3p (miR-17-3p) in uveal melanoma. ⋯ Downregulation of lncRNA PVT1 could potentially promote miR-17-3p expression to suppress tumorigenesis and development of uveal melanoma by activating the p53 signaling pathway through binding to MDM2.
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Invest. Ophthalmol. Vis. Sci. · Oct 2019
Blast Preconditioning Protects Retinal Ganglion Cells and Reveals Targets for Prevention of Neurodegeneration Following Blast-Mediated Traumatic Brian Injury.
The purpose of this study was to examine the effect of multiple blast exposures and blast preconditioning on the structure and function of retinal ganglion cells (RGCs), to identify molecular pathways that contribute to RGC loss, and to evaluate the role of kynurenine-3-monooxygenase (KMO) inhibition on RGC structure and function. ⋯ Preconditioning protects RGC from blast injury. Protective effects appear to involve changes in KMO activity, whose inhibition is also protective.
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Invest. Ophthalmol. Vis. Sci. · Jun 2019
Blast-Mediated Traumatic Brain Injury Exacerbates Retinal Damage and Amyloidosis in the APPswePSENd19e Mouse Model of Alzheimer's Disease.
Traumatic brain injury (TBI) is a risk factor for developing chronic neurodegenerative conditions including Alzheimer's disease (AD). The purpose of this study was to examine chronic effects of blast TBI on retinal ganglion cells (RGC), optic nerve, and brain amyloid load in a mouse model of AD amyloidosis. ⋯ When combined with a genetic susceptibility for developing amyloidosis of AD, blast TBI exposure leads to earlier RGC and optic nerve damage associated with modest but detectable increase in cerebral cortical Aβ pathology. These findings suggest that genetic risk factors for AD may increase the sensitivity of the retina to blast-mediated damage.