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Updated: Apr 26, 2026
Imaging Ca2+ Dynamics in Cone Photoreceptor Axon Terminals of the Mouse Retina
Published on: May 6, 2015
A mouse model for studying cone photoreceptor pathologies
Marijana Samardzija1, Christian Caprara2, Severin R Heynen3
1Laboratory for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Schlieren, Switzerland.
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.
Insights
A new mouse model with a functional all-cone retina was developed. This model, R91W;Nrl(-/-), is crucial for studying cone degeneration diseases.
Area of Science:
- Ophthalmology and visual neuroscience
- Genetics and animal models
- Photoreceptor biology
Background:
- Cone photoreceptor degeneration is poorly understood due to limited animal models.
- Nrl knockout mice exclusively develop cone photoreceptors but have abnormal retinal morphology.
- Previous models like Rpe65(-/-);Nrl(-/-) lacked function and had no rosettes.
Purpose of the Study:
- To create a functional, morphologically well-structured all-cone retina mouse model.
- To enable the study of cone degeneration mechanisms and related diseases.
- To generate R91W;Nrl(-/-) double-mutant mice expressing a hypomorphic Rpe65 allele.
Main Methods:
- Morphological analysis (light and electron microscopy).
- Functional assessment (electroretinography, optomotor response).
- Molecular and biochemical analyses (immunofluorescence, RT-PCR, HPLC).
Main Results:
- The R91W;Nrl(-/-) all-cone retina is functional and stable with minimal degeneration.
- Reduced visual chromophore levels prevented rosette formation and maintained retinal function.
- Cone degeneration was successfully induced and analyzed in modified mutant lines.
Conclusions:
- The R91W;Nrl(-/-) mouse model provides a functional, morphologically intact all-cone retina.
- This model is valuable for investigating the causes of cone degeneration diseases.
- Reduced chromophore levels are key to preventing structural defects and maintaining function.
