Universität zu Köln

Michalakis, Stylianos ORCID: 0000-0001-5092-9238, Muehlfriedel, Regine, Tanimoto, Naoyuki, Krishnamoorthy, Vidhyasankar, Koch, Susanne ORCID: 0000-0001-9966-113X, Fischer, M. Dominik, Becirovic, Elvir ORCID: 0000-0001-8801-0649, Bai, Lin, Huber, Gesine, Beck, Susanne C., Fahl, Edda, Buening, Hildegard, Paquet-Durand, Francois ORCID: 0000-0001-7355-5742, Zong, Xiangang, Gollisch, Tim ORCID: 0000-0003-3998-533X, Biel, Martin and Seeliger, Mathias W. (2010). Restoration of Cone Vision in the CNGA3(-/-) Mouse Model of Congenital Complete Lack of Cone Photoreceptor Function. Mol. Ther., 18 (12). S. 2057 - 2064. CAMBRIDGE: CELL PRESS. ISSN 1525-0024

Full text not available from this repository.

Abstract

Congenital absence of cone photoreceptor function is associated with strongly impaired daylight vision and loss of color discrimination in human achromatopsia. Here, we introduce viral gene replacement therapy as a potential treatment for this disease in the CNGA3(-/-) mouse model. We show that such therapy can restore cone-specific visual processing in the central nervous system even if cone photoreceptors had been nonfunctional from birth. The restoration of cone vision was assessed at different stages along the visual pathway. Treated CNGA3(-/-) mice were able to generate cone photoreceptor responses and to transfer these signals to bipolar cells. In support, we found morphologically that treated cones expressed regular cyclic nucleotide-gated (CNG) channel complexes and opsins in outer segments, which previously they did not. Moreover, expression of CNGA3 normalized cyclic guanosine monophosphate (cGMP) levels in cones, delayed cone cell death and reduced the inflammatory response of Muller glia cells that is typical of retinal degenerations. Furthermore, ganglion cells from treated, but not from untreated, CNGA3(-/-) mice displayed cone-driven, light-evoked, spiking activity, indicating that signals generated in the outer retina are transmitted to the brain. Finally, we demonstrate that this newly acquired sensory information was translated into cone-mediated, vision-guided behavior.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Michalakis, Stylianos UNSPECIFIED orcid.org/0000-0001-5092-9238 UNSPECIFIED Muehlfriedel, Regine UNSPECIFIED UNSPECIFIED UNSPECIFIED Tanimoto, Naoyuki UNSPECIFIED UNSPECIFIED UNSPECIFIED Krishnamoorthy, Vidhyasankar UNSPECIFIED UNSPECIFIED UNSPECIFIED Koch, Susanne UNSPECIFIED orcid.org/0000-0001-9966-113X UNSPECIFIED Fischer, M. Dominik UNSPECIFIED UNSPECIFIED UNSPECIFIED Becirovic, Elvir UNSPECIFIED orcid.org/0000-0001-8801-0649 UNSPECIFIED Bai, Lin UNSPECIFIED UNSPECIFIED UNSPECIFIED Huber, Gesine UNSPECIFIED UNSPECIFIED UNSPECIFIED Beck, Susanne C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fahl, Edda UNSPECIFIED UNSPECIFIED UNSPECIFIED Buening, Hildegard UNSPECIFIED UNSPECIFIED UNSPECIFIED Paquet-Durand, Francois UNSPECIFIED orcid.org/0000-0001-7355-5742 UNSPECIFIED Zong, Xiangang UNSPECIFIED UNSPECIFIED UNSPECIFIED Gollisch, Tim UNSPECIFIED orcid.org/0000-0003-3998-533X UNSPECIFIED Biel, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Seeliger, Mathias W. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-491908
DOI:	10.1038/mt.2010.149
Journal or Publication Title:	Mol. Ther.
Volume:	18
Number:	12
Page Range:	S. 2057 - 2064
Date:	2010
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1525-0024
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language COLOR-VISION; MICE LACKING; RETINAL DEGENERATION; MOLECULAR-BASIS; ALPHA-SUBUNIT; GENE-THERAPY; MUTATIONS; ROD; ACHROMATOPSIA; VECTORS Multiple languages Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49190