ORCID Profile
0000-0003-3021-7991
Current Organisations
University of Western Australia
,
The Harry Perkins Institute of Medical Research
,
Lions Eye Institute
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Publisher: American Astronomical Society
Date: 28-07-2023
Abstract: The global network of gravitational-wave observatories now includes five detectors, namely LIGO Hanford, LIGO Livingston, Virgo, KAGRA, and GEO 600. These detectors collected data during their third observing run, O3, composed of three phases: O3a starting in 2019 April and lasting six months, O3b starting in 2019 November and lasting five months, and O3GK starting in 2020 April and lasting two weeks. In this paper we describe these data and various other science products that can be freely accessed through the Gravitational Wave Open Science Center at gwosc.org . The main data set, consisting of the gravitational-wave strain time series that contains the astrophysical signals, is released together with supporting data useful for their analysis and documentation, tutorials, as well as analysis software packages.
Publisher: Cold Spring Harbor Laboratory
Date: 09-02-2022
DOI: 10.1101/2022.02.07.479069
Abstract: Inherited retinal diseases (IRDs) are a heterogeneous group of blinding disorders, which result in dysfunction or death of the light-sensing cone and rod photoreceptors. Despite in idual IRDs being rare, collectively, they affect up to 1:2000 people worldwide, causing a significant socioeconomic burden, especially when cone-mediated central vision is affected. This study uses the Pde6c cpfl1 mouse model of achromatopsia, a cone-specific vision loss IRD, to investigate the potential gene-independent therapeutic benefits of a histone demethylase inhibitor GSK-J4 on cone cell survival. We investigated the effects of GSK-J4 treatment on cone cell survival in vivo and ex vivo and changes in cone-specific gene expression via single-cell RNA sequencing. A single intravitreal GSK-J4 injection led to transcriptional changes in pathways involved in mitochondrial dysfunction, endoplasmic reticulum stress, among other key epigenetic pathways, highlighting the complex interplay between methylation and acetylation in healthy and diseased cones. Furthermore, continuous administration of GSK-J4 in retinal explants increased cone survival. Our results suggest that IRD-affected cones respond positively to epigenetic modulation of histones, indicating the potential of this approach in the development of a broad class of novel therapies to slow cone degeneration.
Publisher: Frontiers Media SA
Date: 04-08-2023
DOI: 10.3389/FCELL.2023.1224078
Abstract: Elucidation of the cellular changes that occur in degenerating photoreceptors of people with inherited retinal diseases (IRDs) has been a focus for many research teams, leading to numerous theories on how these changes affect the cell death process. What is clearly emerging from these studies is that there are common denominators across multiple models of IRD, regardless of the underlying genetic mutation. These common markers could open avenues for broad neuroprotective therapeutics to prevent photoreceptor loss and preserve functional vision. In recent years, the role of epigenetic modifications contributing to the pathology of IRDs has been a particular point of interest, due to many studies noting changes in these epigenetic modifications, which coincide with photoreceptor cell death. This review will discuss the two broad categories of epigenetic changes, DNA methylation and histone modifications, that have received particular attention in IRD models. We will review the altered epigenetic regulatory events that are believed to contribute to cell death in IRDs and discuss the therapeutic potential of targeting these alterations.
Publisher: Springer Science and Business Media LLC
Date: 10-07-2022
DOI: 10.1007/S00018-022-04436-6
Abstract: Inherited retinal diseases (IRDs) are a heterogeneous group of blinding disorders, which result in dysfunction or death of the light-sensing cone and rod photoreceptors. Despite in idual IRDs (Inherited retinal disease) being rare, collectively, they affect up to 1:2000 people worldwide, causing a significant socioeconomic burden, especially when cone-mediated central vision is affected. This study uses the Pde6c cpfl1 mouse model of achromatopsia, a cone-specific vision loss IRD (Inherited retinal disease), to investigate the potential gene-independent therapeutic benefits of a histone demethylase inhibitor GSK-J4 on cone cell survival. We investigated the effects of GSK-J4 treatment on cone cell survival in vivo and ex vivo and changes in cone-specific gene expression via single-cell RNA sequencing. A single intravitreal GSK-J4 injection led to transcriptional changes in pathways involved in mitochondrial dysfunction, endoplasmic reticulum stress, among other key epigenetic pathways, highlighting the complex interplay between methylation and acetylation in healthy and diseased cones. Furthermore, continuous administration of GSK-J4 in retinal explants increased cone survival. Our results suggest that IRD (Inherited retinal disease)-affected cones respond positively to epigenetic modulation of histones, indicating the potential of this approach in developing a broad class of novel therapies to slow cone degeneration.
Publisher: American Chemical Society (ACS)
Date: 08-01-2009
DOI: 10.1021/JE8009607
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 18-08-2020
DOI: 10.1167/TVST.9.9.28
No related grants have been discovered for Annie Miller.