ORCID Profile
0000-0002-9277-7823
Current Organisations
The Chinese University of Hong Kong
,
University of Melbourne
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Publications
Immunolocalization of the P2X4 receptor on neurons and glia in the mammalian retina
Publisher: Elsevier BV
Date: 09-2014
DOI: 10.1016/J.NEUROSCIENCE.2014.06.055
Abstract: Extracellular adenosine 5'-triphosphate (eATP) acts as a neurotransmitter within the retina and brain, activating a range of ionotropic P2X and metabotropic P2Y receptors. In this study, the specific localization of the P2X4 receptor (P2X4-R) subunit was evaluated in the retina using fluorescence immunohistochemistry and pre-embedding immuno-electron microscopy. Punctate P2X4-R labeling was largely localized to the inner and outer plexiform layers of mouse, rat and cat retinae. In the mouse outer retina, double-labeling of P2X4-R with the horizontal cell marker, calbindin, revealed P2X4-R immunoreactivity (P2X4-R-IR) on horizontal cell somata and processes. In the inner retina, P2X4-R expression was found closely associated with rod and cone bipolar cell terminals, and the punctate labeling was observed on calretinin-positive amacrine cells. Using immuno-electron microscopy, P2X4-Rs were observed on processes post-synaptic to photoreceptor and bipolar cell terminals, likely representing horizontal, amacrine and ganglion cells, respectively. Furthermore, P2X4-R expression was also observed on Müller cells, astrocytes and microglia. These data suggest a role for P2X4-Rs in the lateral inhibitory pathways of the retina, modulating neuronal function of photoreceptors and bipolar cells. The expression on macro- and microglial cells implicates a role for P2X4-Rs in glial signaling, tissue homeostasis and immunosurveillance within the mammalian retina.
Ccl2/Cx3cr1 Knockout Mice Have Inner Retinal Dysfunction but Are Not an Accelerated Model of AMD
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 27-11-2012
Abstract: The chemokine, Ccl2, and the fractalkine receptor, Cx3cr1, have both been implicated in the pathogenesis of age related macular degeneration (AMD), with mice lacking both genes exhibiting features of AMD by 3 months of age. However, recent reports indicate that this ascribed phenotype is due to the presence of a retinal degeneration mutation (crb1(rd8/rd8), rd8) on the background strain. Our aim was to characterize the retinal effects of lack of Ccl2 and Cx3cr1 (Ccl2(-/-)/Cx3cr1(EGFP/EGFP), CDKO-mice), in mice without the rd8 mutation. Nine-month-old, CDKO and wildtype C57blk6J mice were investigated for retinal fundus appearance and histology. The function of the rod and cone pathways was assessed using the ERG. The CDKO mice did not develop lesions in the retinal fundus, and the ultrastructure of Bruch's membrane and the RPE were similar to that of C57blk6J mice. From the ERG, there was no change in the litude of the rod photoreceptor response, or in the rod or cone post-photoreceptor b-wave. However, the rod and cone ERG oscillatory potentials were significantly reduced in the CDKO animals, a phenotype apparent in Cx3cr1(EGFP/EGFP)- but not Ccl2(-/-)-founder lines. This correlated with aberrant amacrine cell morphology in the CDKO mice. In addition, Müller cells were gliotic and microglial morphology subtly altered, indicative of retinal stress. These results suggest that in the absence of the rd8 mutation, the CDKO-mouse has a mild inner retinal phenotype characterized by altered amacrine cell function, but that it is not an accelerated model of AMD.
Vesicular expression and release of ATP from dopaminergic neurons of the mouse retina and midbrain
Publisher: Frontiers Media SA
Date: 06-10-2015
Studying age-related macular degeneration using animal models.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2014
Amyloid Precursor Protein Is Required for Normal Function of the Rod and Cone Pathways in the Mouse Retina
Publisher: Public Library of Science (PLoS)
Date: 18-01-2012
Adenosine triphosphate-induced photoreceptor death and retinal remodeling in rats.
Publisher: Wiley
Date: 03-04-2014
DOI: 10.1002/CNE.23558
Localization and Possible Function of P2X Receptors in Normal and Diseased Retinae.
Publisher: Mary Ann Liebert Inc
Date: 10-2016
Abstract: Purines, when present in the extracellular space, can mediate fast neurotransmission in the retina and central nervous system. Over the last decade there has been emerging evidence for the expression of P2X and P2Y receptors in a range of retinal neuronal subtypes. These results have highlighted important roles for purines in modulating specific retinal circuits, including the rod pathway and amacrine cell circuits. Traditionally, synaptic release of adenosine triphosphate (ATP) involves the novel anion vesicular nucleotide transporter, VNUT, which has recently been identified in a single wide-field amacrine cell population. In addition, nontraditional, conductive mechanisms of release have also been described in the retina. In the synapse, the enzymes involved in rapid degradation of purines are present in both plexiform layers of the retina. A role for P2X receptors in retinal diseases has also emerged recently. High concentrations of ATP lead to photoreceptor loss, through mechanisms involving P2X
Assessment of Retinal Function and Morphology in Aging Ccl2 Knockout Mice
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 27-01-2015
Abstract: The chemokine Ccl2, or monocyte chemoattractant protein-1 (MCP-1), has previously been identified as playing a potential role in many ocular diseases however, its role in mice is less clear. We sought to correlate changes in retinal pigment epithelium (RPE) and retinal morphology with changes in function in aging Ccl2(-/-) mice. Ccl2(-/-) mice on a C57BL6J background were genotyped for Crb1(rd8/rd8) and were free of this mutation. Ccl2(-/-) mice and wild-type (WT) C57BL6J mice were investigated for changes in the retinal fundus and histology as a function of age. The function of the rod and cone pathways, and the rate of dark adaptation, was assessed using the electroretinogram (ERG) up to 15 months of age. Fifteen-month-old Ccl2(-/-) mice had fundus lesions, more subretinal microglia/macrophages, and an increase in RPE cell size, indicative of RPE cell loss, when compared with WT mice. Within the retina, gross morphology was normal but there was an increase in Müller cell gliosis and microglial activation. These morphological changes in the Ccl2(-/-) RPE/retina did not correlate with a change in either rod or cone ERG pathway function, or with the rate of dark adaptation. These data show that Ccl2 is important for preserving RPE and glial morphology with age, yet retinal function and gross morphology are maintained. Altered signaling in this chemokine pathway may, however, increase RPE and retinal vulnerability to disease.
Nanosecond Laser Treatment for Age-Related Macular Degeneration Does Not Induce Focal Vision Loss or New Vessel Growth in the Retina
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 02-2018
Abstract: Subthreshold, nanosecond pulsed laser treatment shows promise as a treatment for age-related macular degeneration (AMD) however, the safety profile needs to be robustly examined. The aim of this study was to investigate the effects of laser treatment in humans and mice. Patients with AMD were treated with nanosecond pulsed laser at subthreshold (no visible retinal effect) energy doses (0.15-0.45 mJ) and retinal sensitivity was assessed with microperimetry. Adult C57BL6J mice were treated at subthreshold (0.065 mJ) and suprathreshold (photoreceptor loss, 0.5 mJ) energy settings. The retinal and vascular responses were analyzed by fundus imaging, histologic assessment, and quantitative PCR. Microperimetry analysis showed laser treatment had no effect on retinal sensitivity under treated areas in patients 6 months to 7 years after treatment. In mice, subthreshold laser treatment induced RPE loss at 5 hours, and by 7 days the RPE had retiled. Fundus imaging showed reduced RPE pigmentation but no change in retinal thickness up to 3 months. Electron microscopy revealed changes in melanosomes in the RPE, but Bruch's membrane was intact across the laser regions. Histologic analysis showed normal vasculature and no neovascularization. Suprathreshold laser treatment did not induce changes in angiogenic genes associated with neovascularization. Instead pigment epithelium-derived factor, an antiangiogenic factor, was upregulated. In humans, low-energy, nanosecond pulsed laser treatment is not damaging to local retinal sensitivity. In mice, treatment does not damage Bruch's membrane or induce neovascularization, highlighting a reduced side effect profile of this nanosecond laser when used in a subthreshold manner.
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Related Funding Activities
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