Adenosine tri-phosphate induced photoreceptor death and retinal remodelling in rats

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dc.contributor.authorVessey, Kirstan
dc.contributor.authorGreferath, Ursula
dc.contributor.authorAplin, Felix
dc.contributor.authorJobling, Andrew
dc.contributor.authorPhipps, Joanna
dc.contributor.authorHo, Tracy
dc.contributor.authorDe longh, Robbert
dc.contributor.authorFletcher, Erica
dc.date.accessioned2015-09-21T06:38:17Z
dc.date.available2015-09-21T06:38:17Z
dc.date.issued2014-09
dc.description.abstractMany common causes of blindness involve the death of retinal photoreceptors, followed by progressive inner retinal cell remodeling. For an inducible model of retinal degeneration to be useful, it must recapitulate these changes. Intravitreal administration of adenosine triphosphate (ATP) has recently been found to induce acute photoreceptor death. The aim of this study was to characterize the chronic effects of ATP on retinal integrity. Five-week-old, dark agouti rats were administered 50 mM ATP into the vitreous of one eye and saline into the other. Vision was assessed using the electroretinogram and optokinetic response and retinal morphology investigated via histology. ATP caused significant loss of visual function within 1 day and loss of 50% of the photoreceptors within 1 week. At 3 months, 80% of photoreceptor nuclei were lost, and total photoreceptor loss occurred by 6 months. The degeneration and remodeling were similar to those found in heritable retinal dystrophies and age-related macular degeneration and included inner retinal neuronal loss, migration, and formation of new synapses; Müller cell gliosis, migration, and scarring; blood vessel loss; and retinal pigment epithelium migration. In addition, extreme degeneration and remodeling events, such as neuronal and glial migration outside the neural retina and proliferative changes in glial cells, were observed. These extreme changes were also observed in the 2-year-old P23H rhodopsin transgenic rat model of retinitis pigmentosa. This ATP-induced model of retinal degeneration may provide a valuable tool for developing pharmaceutical therapies or for testing electronic implants aimed at restoring vision.en_US
dc.description.sponsorshipAustralian Research Council (ARC) Special Research Initiative (SRI) in Bionic Vision Science and Technology (to Bionic Vision Australia); Grant sponsor: National Health and Medical Research Council of Australia; Grant number: 1021042.en_US
dc.identifier.citationVessey, K. A., U. Greferath, F. P. Aplin, A. I. Jobling, J. A. Phipps, T. Ho, R. U. de Iongh and E. L. Fletcher (2014). Adenosine tri-phosphate induced photoreceptor death and retinal remodelling in rats. Journal of Comparative Neurology 522: 2928-2950.en_US
dc.identifier.urihttp://repository.bionicsinstitute.org:8080/handle/123456789/134
dc.language.isoenen_US
dc.publisherWiley Periodicals Incen_US
dc.subjectretinitis pigmentosaen_US
dc.subjectage-related macular degenerationen_US
dc.subjectneural degenerationen_US
dc.subjectretinal remodelingen_US
dc.subjectrodenten_US
dc.titleAdenosine tri-phosphate induced photoreceptor death and retinal remodelling in ratsen_US
dc.typeArticleen_US
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