Rapid Recovery of Visual Function Associated with Blue Cone Ablation in Zebrafish
Hurdles in the treatment of retinal degeneration include managing the functional rewiring of surviving photoreceptors and integration of any newly added cells into the remaining second-order retinal neurons. Zebrafish are the premier genetic model for such questions, and we present two new transgeni...
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description | Hurdles in the treatment of retinal degeneration include managing the functional rewiring of surviving photoreceptors and integration of any newly added cells into the remaining second-order retinal neurons. Zebrafish are the premier genetic model for such questions, and we present two new transgenic lines allowing us to contrast vision loss and recovery following conditional ablation of specific cone types: UV or blue cones. The ablation of each cone type proved to be thorough (killing 80% of cells in each intended cone class), specific, and cell-autonomous. We assessed the loss and recovery of vision in larvae via the optomotor behavioural response (OMR). This visually mediated behaviour decreased to about 5% or 20% of control levels following ablation of UV or blue cones, respectively (P |
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Zebrafish are the premier genetic model for such questions, and we present two new transgenic lines allowing us to contrast vision loss and recovery following conditional ablation of specific cone types: UV or blue cones. The ablation of each cone type proved to be thorough (killing 80% of cells in each intended cone class), specific, and cell-autonomous. We assessed the loss and recovery of vision in larvae via the optomotor behavioural response (OMR). This visually mediated behaviour decreased to about 5% or 20% of control levels following ablation of UV or blue cones, respectively (P<0.05). We further assessed ocular photoreception by measuring the effects of UV light on body pigmentation, and observed that photoreceptor deficits and recovery occurred (p<0.01) with a timeline coincident to the OMR results. This corroborated and extended previous conclusions that UV cones are required photoreceptors for modulating body pigmentation, addressing assumptions that were unavoidable in previous experiments. Functional vision recovery following UV cone ablation was robust, as measured by both assays, returning to control levels within four days. In contrast, robust functional recovery following blue cone ablation was unexpectedly rapid, returning to normal levels within 24 hours after ablation. Ablation of cones led to increased proliferation in the retina, though the rapid recovery of vision following blue cone ablation was demonstrated to not be mediated by blue cone regeneration. Thus rapid visual recovery occurs following ablation of some, but not all, cone subtypes, suggesting an opportunity to contrast and dissect the sources and mechanisms of outer retinal recovery during cone photoreceptor death and regeneration.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0166932</identifier><identifier>PMID: 27893779</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Ablation (Surgery) ; Ablation Techniques ; Animals ; Animals, Genetically Modified ; Apoptosis ; Biology and Life Sciences ; Cell Death ; Cell Proliferation ; Cones ; Danio rerio ; Degeneration ; Genetics ; Larva ; Larvae ; Medicine and Health Sciences ; Melanins - metabolism ; Metronidazole - pharmacology ; Nitroreductases - genetics ; Nitroreductases - metabolism ; Oncorhynchus mykiss ; Photoreception ; Photoreceptors ; Physical Sciences ; Physiological aspects ; Pigmentation ; Recovery ; Recovery (Medical) ; Recovery of function ; Regeneration ; Research and Analysis Methods ; Retina ; Retina - cytology ; Retinal Cone Photoreceptor Cells - drug effects ; Retinal Cone Photoreceptor Cells - physiology ; Retinal Degeneration ; Rewiring ; Social Sciences ; Stem cells ; Thyroid gland ; Trout ; Ultraviolet radiation ; Ultraviolet Rays ; Vision ; Vision, Ocular - physiology ; Visual perception ; Zebrafish ; Zebrafish - genetics</subject><ispartof>PloS one, 2016-11, Vol.11 (11), p.e0166932-e0166932</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Hagerman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Hagerman et al 2016 Hagerman et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c725t-14228f21d4f263646ae32208ea205a7542b6b694e3bde5f30eafa97ee0f3e61c3</citedby><cites>FETCH-LOGICAL-c725t-14228f21d4f263646ae32208ea205a7542b6b694e3bde5f30eafa97ee0f3e61c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125653/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125653/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27893779$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hagerman, Gordon F</creatorcontrib><creatorcontrib>Noel, Nicole C L</creatorcontrib><creatorcontrib>Cao, Sylvia Y</creatorcontrib><creatorcontrib>DuVal, Michèle G</creatorcontrib><creatorcontrib>Oel, A Phillip</creatorcontrib><creatorcontrib>Allison, W Ted</creatorcontrib><title>Rapid Recovery of Visual Function Associated with Blue Cone Ablation in Zebrafish</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Hurdles in the treatment of retinal degeneration include managing the functional rewiring of surviving photoreceptors and integration of any newly added cells into the remaining second-order retinal neurons. 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Zebrafish are the premier genetic model for such questions, and we present two new transgenic lines allowing us to contrast vision loss and recovery following conditional ablation of specific cone types: UV or blue cones. The ablation of each cone type proved to be thorough (killing 80% of cells in each intended cone class), specific, and cell-autonomous. We assessed the loss and recovery of vision in larvae via the optomotor behavioural response (OMR). This visually mediated behaviour decreased to about 5% or 20% of control levels following ablation of UV or blue cones, respectively (P<0.05). We further assessed ocular photoreception by measuring the effects of UV light on body pigmentation, and observed that photoreceptor deficits and recovery occurred (p<0.01) with a timeline coincident to the OMR results. This corroborated and extended previous conclusions that UV cones are required photoreceptors for modulating body pigmentation, addressing assumptions that were unavoidable in previous experiments. Functional vision recovery following UV cone ablation was robust, as measured by both assays, returning to control levels within four days. In contrast, robust functional recovery following blue cone ablation was unexpectedly rapid, returning to normal levels within 24 hours after ablation. Ablation of cones led to increased proliferation in the retina, though the rapid recovery of vision following blue cone ablation was demonstrated to not be mediated by blue cone regeneration. 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subjects | Ablation (Surgery) Ablation Techniques Animals Animals, Genetically Modified Apoptosis Biology and Life Sciences Cell Death Cell Proliferation Cones Danio rerio Degeneration Genetics Larva Larvae Medicine and Health Sciences Melanins - metabolism Metronidazole - pharmacology Nitroreductases - genetics Nitroreductases - metabolism Oncorhynchus mykiss Photoreception Photoreceptors Physical Sciences Physiological aspects Pigmentation Recovery Recovery (Medical) Recovery of function Regeneration Research and Analysis Methods Retina Retina - cytology Retinal Cone Photoreceptor Cells - drug effects Retinal Cone Photoreceptor Cells - physiology Retinal Degeneration Rewiring Social Sciences Stem cells Thyroid gland Trout Ultraviolet radiation Ultraviolet Rays Vision Vision, Ocular - physiology Visual perception Zebrafish Zebrafish - genetics |
title | Rapid Recovery of Visual Function Associated with Blue Cone Ablation in Zebrafish |
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