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dc.contributor.authorKakavand, K
dc.contributor.authorJobling, AI
dc.contributor.authorGreferath, U
dc.contributor.authorVessey, KA
dc.contributor.authorde Iongh, RU
dc.contributor.authorFletcher, EL
dc.date.accessioned2020-12-09T22:41:58Z
dc.date.available2020-12-09T22:41:58Z
dc.date.issued2020-11-03
dc.identifier.citationKakavand, K., Jobling, A. I., Greferath, U., Vessey, K. A., de Iongh, R. U. & Fletcher, E. L. (2020). Photoreceptor Degeneration in Pro23His Transgenic Rats (Line 3) Involves Autophagic and Necroptotic Mechanisms. FRONTIERS IN NEUROSCIENCE, 14, https://doi.org/10.3389/fnins.2020.581579.
dc.identifier.issn1662-4548
dc.identifier.urihttp://hdl.handle.net/11343/253045
dc.description.abstractPhotoreceptor death contributes to 50% of irreversible vision loss in the western world. Pro23His (P23H) transgenic albino rat strains are widely used models for the most common rhodopsin gene mutation associated with the autosomal dominant form of retinitis pigmentosa. However, the mechanism(s) by which photoreceptor death occurs are not well understood and were the principal aim of this study. We first used electroretinogram recording and optical coherence tomography to confirm the time course of functional and structural loss. Electroretinogram analyses revealed significantly decreased rod photoreceptor (a-wave), bipolar cell (b-wave) and amacrine cell responses (oscillatory potentials) from P30 onward. The cone-mediated b-wave was also decreased from P30. TUNEL analysis showed extensive cell death at P18, with continued labeling detected until P30. Focused gene expression arrays indicated activation of, apoptosis, autophagy and necroptosis in whole retina from P14-18. However, analysis of mitochondrial permeability changes (ΔΨm) using JC-1 dye, combined with immunofluorescence markers for caspase-dependent (cleaved caspase-3) and caspase-independent (AIF) cell death pathways, indicated mitochondrial-mediated cell death was not a major contributor to photoreceptor death. By contrast, reverse-phase protein array data combined with RIPK3 and phospho-MLKL immunofluorescence indicated widespread necroptosis as the predominant mechanism of photoreceptor death. These findings highlight the complexity of mechanisms involved in photoreceptor death in the Pro23His rat model of degeneration and suggest therapies that target necroptosis should be considered for their potential to reduce photoreceptor death.
dc.languageEnglish
dc.publisherFRONTIERS MEDIA SA
dc.titlePhotoreceptor Degeneration in Pro23His Transgenic Rats (Line 3) Involves Autophagic and Necroptotic Mechanisms
dc.typeJournal Article
dc.identifier.doi10.3389/fnins.2020.581579
melbourne.affiliation.departmentAnatomy and Neuroscience
melbourne.source.titleFrontiers in Neuroscience
melbourne.source.volume14
dc.rights.licenseCC BY
melbourne.elementsid1481156
melbourne.contributor.authorFletcher, Erica
melbourne.contributor.authorGreferath, Ursula
melbourne.contributor.authorde Iongh, Robbert
melbourne.contributor.authorVessey, Kirstan
melbourne.contributor.authorJobling, Andrew
dc.identifier.eissn1662-453X
melbourne.accessrightsOpen Access


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