ARTICLE | doi:10.20944/preprints202210.0123.v1
Subject: Engineering, Biomedical & Chemical Engineering Keywords: biomedical research; classification; machine learning; electroretinography; electroretinogram; ERG
Online: 10 October 2022 (11:11:37 CEST)
The electroretinography (ERG) is a diagnostic test that measures the electrical activity of the retina in response to a light stimulus. This test has a long history and has been extensively studied among years. Dr. James Dewar recorded the first electroretinogram signal in 1873. Later he described signal analysis using 4 components, namely amplitude, and latency of a-wave and b-wave. Nowadays, the international electrophysiology community has established the standard for electroretinography in 2008. However, from the point of view of signal analysis, the major change did not happen. ERG analysis is still based on the 4 components evaluation. The article describes ERG database including the classification of signals by using advanced analysis of electroretinograms based on wavelet scalogram processing. To implement an extended analysis of the ERG, the parameters extracted from the wavelet scalogram of the signal were obtained using digital image processing and machine learning methods. The results of the study show that the proposed algorithm implements the classification of adult electroretinogram signals by 19% more accurately and pediatric signals by 20% more accurately than the classical algorithm. The promising use of ERG is differential diagnostics, which may also be used in preclinical toxicology and experimental modeling. The problem of developing methods for electrophysiological signals analysis in ophthalmology is associated with the complex morphological structure of electrophysiological signals components, due to the generation of retina cell electrical responses to light stimulus.
COMMUNICATION | doi:10.20944/preprints202104.0273.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Dry-AMD; oxidative stress; MnSOD; RPE; retinal degeneration; Erythropoietin; gene therapy; Animal model; AAV; ERG
Online: 12 April 2021 (09:37:18 CEST)
Erythropoietin (EPO) protects cells by inhibiting apoptosis, oxidative stress and inflammation in several models of retinal degeneration. In this study, we demonstrate the effects of recombinant Adeno Associated Virus (AAV) vector-mediated delivery of a modified form of erythropoietin (EPO-R76E) in an established mouse model of dry-AMD in which retinal degeneration is induced by RPE oxidative stress. Experimental vector AAV-EPO-R76E and control vector AAV-GFP were packaged into serotype-1 (AAV1) to enable RPE selective expression. RPE oxidative stress-mediated retinal degeneration was induced by exon specific deletion of the protective enzyme MnSOD (encoded by Sod2) by cre/lox mechanism. Experimental mice received subretinal injection of AAV-EPO-R76E in the right eye and AAV-GFP in the left eye. Western blotting of RPE/Choroid protein samples from AAV-EPO-R76E injected eyes showed RPE specific exogenous protein expression. Retinal degeneration was monitored by electroretinography (ERG). EPO-R76E over-expression in RPE delayed the progressive retinal degeneration as measured by light microscopy in RPE specific Sod2 knockout mice. Delivery of EPO-R76E vector can be used as a tool to prevent retinal degeneration induced by RPE oxidative stress as seen in this mouse model.
ARTICLE | doi:10.20944/preprints202208.0030.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: ascending aorta aneurysm; bicuspid aorta valve; tricuspid aorta valve; ERG transcriptional factor pathway; TGF-β-SMAD, Notch, and NO pathways modulation.
Online: 2 August 2022 (03:43:22 CEST)
Abstract: The pathobiology of ascending aorta aneurysms (AAA) onset and progression is not well understood and only partially characterized. AAA are also complicated in case of bicuspid aorta valve (BAV) anatomy. There is emerging evidence about the crucial role of endothelium-related pathways, which show in AAA an altered expression and function. Here, we examined the involvement of ERG-related pathways in the differential progression of disease in aortic tissues from patients having a BAV or tricuspid aorta valve (TAV) with or without AAA. Our findings identified ERG as a novel endothelial-specific regulator of TGF-β-SMAD, Notch, and NO pathways, by modulating a differential fibrotic or calcified AAA progression in BAV and TAV aortas. We provided evidence that calcification is correlated to different ERG expression (as gene and protein), which appears to be under control of Notch signaling. The latter, when increased, associated with an early calcification in aortas with BAV valve and aneurysmatic, was demonstrated to favor the progression versus severe complications, i.e., dissection or rupture. In TAV aneurysmatic aortas, ERG appeared to modulate fibrosis. Therefore, we proposed that ERG may represent a sensitive tissue biomarker to monitor AAA progression and a target to develop therapeutic strategies and influence surgical procedures.