Journal article
A mouse model for studying cone photoreceptor pathologies.
- Samardzija M Laboratory for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Schlieren, Switzerland.
- Caprara C Laboratory for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Schlieren, Switzerland Center for Neuroscience, University of Zurich, Zurich, Switzerland.
- Heynen SR Laboratory for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Schlieren, Switzerland Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
- Willcox DeParis S Laboratory for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Schlieren, Switzerland.
- Meneau I Laboratory for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Schlieren, Switzerland.
- Traber G Laboratory for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Schlieren, Switzerland.
- Agca C Laboratory for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Schlieren, Switzerland.
- von Lintig J Case Western Reserve University, Cleveland, Ohio, United States.
- Grimm C Laboratory for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Schlieren, Switzerland.
- 2014-07-19
Published in:
- Investigative ophthalmology & visual science. - 2014
AMD
RPE65
cone cell death
mouse model
Animals
Chromatography, High Pressure Liquid
Disease Models, Animal
Electroretinography
Mice, Inbred C57BL
Mice, Knockout
Microscopy, Electron
Retina
Retinal Cone Photoreceptor Cells
Retinal Degeneration
Retinaldehyde
cis-trans-Isomerases
English
PURPOSE
Due to the low abundance of cone photoreceptors in the mouse retina and the scarcity of alternative animal models, little is known about mechanisms of cone degeneration. Nrl knockout mice develop exclusively the cone-type of photoreceptors. However, the cone photoreceptor layer in Nrl(-/-) mice displays an irregular morphology with severe rosette formation. Retinas of Rpe65(-/-);Nrl(-/-) mice have no rosettes due to the lack of 11-cis-retinal, but also are not functional. To develop a model with a functional all-cone retina that is morphologically well structured, we generated R91W;Nrl(-/-) double-mutant mice, which express a hypomorphic Rpe65 allele (R91W).
METHODS
The following analyses were used to characterize the R91W;Nrl(-/-)mice: morphology by light and electron microscopy, protein distribution by immunofluorescence, cone function by electroretinography and optomotor response, RNA levels by RT-PCR, and chromophore levels by HPLC. Cone degeneration was assessed in R91W;Nrl(-/-) mice treated with MNU, and in triple R91W;Nrl(-/-);Cpfl1 and quadruple R91W;Nrl(-/-);Cpfl1;rd10 mutant mice.
RESULTS
The all-cone retina of R91W;Nrl(-/-) mice is functional and relatively stable with only very slow age-related degeneration. Using triple and quadruple mutant mice, or a chemical treatment, we demonstrated that cone degeneration could be induced and analyzed in these mice.
CONCLUSIONS
The reduced levels of visual chromophore prevented rosette formation and sustained function in the R91W;Nrl(-/-) retina. Thus, the R91W;Nrl(-/-) mouse allows study of the etiology of diseases related to cone degeneration in a "morphologically intact" and functional all-cone photoreceptor retina.
Due to the low abundance of cone photoreceptors in the mouse retina and the scarcity of alternative animal models, little is known about mechanisms of cone degeneration. Nrl knockout mice develop exclusively the cone-type of photoreceptors. However, the cone photoreceptor layer in Nrl(-/-) mice displays an irregular morphology with severe rosette formation. Retinas of Rpe65(-/-);Nrl(-/-) mice have no rosettes due to the lack of 11-cis-retinal, but also are not functional. To develop a model with a functional all-cone retina that is morphologically well structured, we generated R91W;Nrl(-/-) double-mutant mice, which express a hypomorphic Rpe65 allele (R91W).
METHODS
The following analyses were used to characterize the R91W;Nrl(-/-)mice: morphology by light and electron microscopy, protein distribution by immunofluorescence, cone function by electroretinography and optomotor response, RNA levels by RT-PCR, and chromophore levels by HPLC. Cone degeneration was assessed in R91W;Nrl(-/-) mice treated with MNU, and in triple R91W;Nrl(-/-);Cpfl1 and quadruple R91W;Nrl(-/-);Cpfl1;rd10 mutant mice.
RESULTS
The all-cone retina of R91W;Nrl(-/-) mice is functional and relatively stable with only very slow age-related degeneration. Using triple and quadruple mutant mice, or a chemical treatment, we demonstrated that cone degeneration could be induced and analyzed in these mice.
CONCLUSIONS
The reduced levels of visual chromophore prevented rosette formation and sustained function in the R91W;Nrl(-/-) retina. Thus, the R91W;Nrl(-/-) mouse allows study of the etiology of diseases related to cone degeneration in a "morphologically intact" and functional all-cone photoreceptor retina.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1167/iovs.14-14789
- PMID 25034607
- Persistent URL
- https://sonar.rero.ch/global/documents/215396
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