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Stem Cell–Derived Photoreceptor Transplants Differentially Integrate Into Mouse Models of Cone-Rod Dystrophy

Overview of attention for article published in Investigative Ophthalmology & Visual Science, June 2016
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Title
Stem Cell–Derived Photoreceptor Transplants Differentially Integrate Into Mouse Models of Cone-Rod Dystrophy
Published in
Investigative Ophthalmology & Visual Science, June 2016
DOI 10.1167/iovs.16-19087
Pubmed ID
Authors

Tiago Santos-Ferreira, Manuela Völkner, Oliver Borsch, Jochen Haas, Peter Cimalla, Praveen Vasudevan, Peter Carmeliet, Denis Corbeil, Stylianos Michalakis, Edmund Koch, Mike O. Karl, Marius Ader

Abstract

Preclinical studies on photoreceptor transplantation provided evidence for restoration of visual function with pluripotent stem cells considered as a potential source for sufficient amounts of donor material. Adequate preclinical models representing retinal disease conditions of potential future patients are needed for translation research. Here we compared transplant integration in mouse models with mild (prominin1-deficient; Prom1-/-) or severe (cone photoreceptor function loss 1/rhodopsin-deficient double-mutant; Cpfl1/Rho-/-) cone-rod degeneration. For photoreceptor transplant production, we combined the mouse embryonic stem cell retinal organoid system with rhodopsin-driven GFP cell labeling by recombinant adeno-associated virus (AAV). Organoid-derived photoreceptors were enriched by CD73-based magnetic-activated cell sorting (MACS) and transplanted subretinally into wild-type, Prom1-/- and Cpfl1/Rho-/- hosts. The survival, maturation, and synapse formation of donor cells was analyzed by immunohistochemistry. Retinal organoids yielded high photoreceptor numbers that were further MACS-enriched to 85% purity. Grafted photoreceptors survived in the subretinal space of all mouse models. Some cells integrated into wild-type as well as Prom1-/- mouse retinas and acquired a mature morphology, expressing rod and synaptic markers in close proximity to second-order neurons. In contrast, in the novel Cpfl1/Rho-/- model with complete photoreceptor degeneration, transplants remained confined to the subretinal space, expressed rod-specific but only reduced synaptic markers, and did not acquire mature morphology. Comparison of photoreceptor grafts in preclinical models with incomplete or complete photoreceptor loss, showed differential transplant success with effective and impaired integration, respectively. Thus, Cpfl1/Rho-/- mice represent a potential benchmark model resembling patients with severe retinal degeneration to optimize photoreceptor replacement therapies.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 101 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 <1%
Israel 1 <1%
Unknown 99 98%

Demographic breakdown

Readers by professional status Count As %
Researcher 26 26%
Student > Ph. D. Student 16 16%
Student > Bachelor 11 11%
Student > Doctoral Student 9 9%
Student > Master 7 7%
Other 12 12%
Unknown 20 20%
Readers by discipline Count As %
Neuroscience 22 22%
Biochemistry, Genetics and Molecular Biology 20 20%
Agricultural and Biological Sciences 16 16%
Medicine and Dentistry 13 13%
Engineering 5 5%
Other 4 4%
Unknown 21 21%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 July 2016.
All research outputs
#19,944,091
of 25,373,627 outputs
Outputs from Investigative Ophthalmology & Visual Science
#5,975
of 7,984 outputs
Outputs of similar age
#267,889
of 366,930 outputs
Outputs of similar age from Investigative Ophthalmology & Visual Science
#94
of 156 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one is in the 18th percentile – i.e., 18% of other outputs scored the same or lower than it.
So far Altmetric has tracked 7,984 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.1. This one is in the 21st percentile – i.e., 21% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 366,930 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 22nd percentile – i.e., 22% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 156 others from the same source and published within six weeks on either side of this one. This one is in the 38th percentile – i.e., 38% of its contemporaries scored the same or lower than it.