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Article: Restoration of visual function in retinal degeneration mice by ectopic expression of melanopsin

TitleRestoration of visual function in retinal degeneration mice by ectopic expression of melanopsin
Authors
KeywordsSpecies Index: Bacteria (Microorganisms)
Mammalia
Mus
Issue Date2008
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings Of The National Academy Of Sciences Of The United States Of America, 2008, v. 105 n. 41, p. 16009-16014 How to Cite?
AbstractThe rod and cone cells of the mammalian retina are the principal photoreceptors for image-forming vision. They transmit information by means of a chain of intermediate cells to the retinal ganglion cells, which in turn send signals from the retina to the brain. Loss of photoreceptor cells, as happens in a number of human diseases, leads to irreversible blindness. In a mouse model (rd/rd) of photoreceptor degeneration, we used a viral vector to express in a large number of retinal ganglion cells the light sensitive protein melanopsin, normally present in only a specialized subset of the cells. Whole-cell patch-clamp recording showed photoresponses in these cells even after degeneration of the photoreceptors and additional pharmacological or Cd 2+ block of synaptic function. Interestingly, similar responses were observed across a wide variety of diverse types of ganglion cell of the retina. The newly melanopsin-expressing ganglion cells provided an enhancement of visual function in rd/rd mice: the pupillary light reflex (PLR) returned almost to normal; the mice showed behavioral avoidance of light in an open-field test, and they could discriminate a light stimulus from a dark one in a two-choice visual discrimination alley. Recovery of the PLR was stable for at least 11 months. It has recently been shown that ectopic retinal expression of a light sensitive bacterial protein, channelrhodopsin-2, can restore neuronal responsiveness and simple visual abilities in rd/rd mice. For therapy in human photodegenerations, channelrhodopsin-2 and melanopsin have different advantages and disadvantages; both proteins (or modifications of them) should be candidates. © 2008 by The National Academy of Sciences of the USA.
Persistent Identifierhttp://hdl.handle.net/10722/90940
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
National Institutes of HealthEY 017169
EY016807
Pew Scholars award
Funding Information:

We thank Aimee Wong and Richard Brown for advice on the testing of mouse visual discriminations and Jeng-Shin Lee and the Harvard vector core for providing the AAV constructs. This work was supported by National Institutes of Health Grants EY 017169 (to R.H.M.) and EY016807 (to S.P.). S.P. was supported by a Pew Scholars award. R.H.M. is a Senior Investigator of Research to Prevent Blindness.

References

 

DC FieldValueLanguage
dc.contributor.authorLin, Ben_HK
dc.contributor.authorKoizumi, Aen_HK
dc.contributor.authorTanaka, Nen_HK
dc.contributor.authorPanda, Sen_HK
dc.contributor.authorMasland, RHen_HK
dc.date.accessioned2010-09-17T10:10:39Z-
dc.date.available2010-09-17T10:10:39Z-
dc.date.issued2008en_HK
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 2008, v. 105 n. 41, p. 16009-16014en_HK
dc.identifier.issn0027-8424en_HK
dc.identifier.urihttp://hdl.handle.net/10722/90940-
dc.description.abstractThe rod and cone cells of the mammalian retina are the principal photoreceptors for image-forming vision. They transmit information by means of a chain of intermediate cells to the retinal ganglion cells, which in turn send signals from the retina to the brain. Loss of photoreceptor cells, as happens in a number of human diseases, leads to irreversible blindness. In a mouse model (rd/rd) of photoreceptor degeneration, we used a viral vector to express in a large number of retinal ganglion cells the light sensitive protein melanopsin, normally present in only a specialized subset of the cells. Whole-cell patch-clamp recording showed photoresponses in these cells even after degeneration of the photoreceptors and additional pharmacological or Cd 2+ block of synaptic function. Interestingly, similar responses were observed across a wide variety of diverse types of ganglion cell of the retina. The newly melanopsin-expressing ganglion cells provided an enhancement of visual function in rd/rd mice: the pupillary light reflex (PLR) returned almost to normal; the mice showed behavioral avoidance of light in an open-field test, and they could discriminate a light stimulus from a dark one in a two-choice visual discrimination alley. Recovery of the PLR was stable for at least 11 months. It has recently been shown that ectopic retinal expression of a light sensitive bacterial protein, channelrhodopsin-2, can restore neuronal responsiveness and simple visual abilities in rd/rd mice. For therapy in human photodegenerations, channelrhodopsin-2 and melanopsin have different advantages and disadvantages; both proteins (or modifications of them) should be candidates. © 2008 by The National Academy of Sciences of the USA.en_HK
dc.languageengen_HK
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_HK
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_HK
dc.subjectSpecies Index: Bacteria (Microorganisms)en_HK
dc.subjectMammaliaen_HK
dc.subjectMusen_HK
dc.titleRestoration of visual function in retinal degeneration mice by ectopic expression of melanopsinen_HK
dc.typeArticleen_HK
dc.identifier.emailLin, B:blin@hku.hken_HK
dc.identifier.authorityLin, B=rp01356en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.0806114105en_HK
dc.identifier.pmid18836071-
dc.identifier.pmcidPMC2572922-
dc.identifier.scopuseid_2-s2.0-57349113014en_HK
dc.identifier.hkuros228172-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-57349113014&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume105en_HK
dc.identifier.issue41en_HK
dc.identifier.spage16009en_HK
dc.identifier.epage16014en_HK
dc.identifier.eissn1091-6490-
dc.identifier.isiWOS:000260240900066-
dc.publisher.placeUnited Statesen_HK
dc.identifier.f10001123390-
dc.identifier.scopusauthoridLin, B=36165916900en_HK
dc.identifier.scopusauthoridKoizumi, A=7101783218en_HK
dc.identifier.scopusauthoridTanaka, N=7404271924en_HK
dc.identifier.scopusauthoridPanda, S=7201766540en_HK
dc.identifier.scopusauthoridMasland, RH=7007167900en_HK

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