Cone Photoreceptor Function Loss-3, a Novel Mouse Model of Achromatopsia Due to a Mutation inGnat2

2006 ◽  
Vol 47 (11) ◽  
pp. 5017 ◽  
Author(s):  
Bo Chang ◽  
Mark S. Dacey ◽  
Norm L. Hawes ◽  
Peter F. Hitchcock ◽  
Ann H. Milam ◽  
...  
Keyword(s):  
Mouse Model ◽  
Cone Photoreceptor ◽  
Function Loss

scholarly journals The cGMP-Dependent Protein Kinase 2 Contributes to Cone Photoreceptor Degeneration in the Cnga3-Deficient Mouse Model of Achromatopsia

2020 ◽  
Vol 22 (1) ◽  
pp. 52
Author(s):  
Mirja Koch ◽  
Constanze Scheel ◽  
Hongwei Ma ◽  
Fan Yang ◽  
Michael Stadlmeier ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mouse Model ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Cone Photoreceptor ◽  
Photoreceptor Degeneration ◽  
Dependent Protein Kinase ◽  
Genetic Ablation ◽  
Cgmp Dependent Protein Kinase ◽  
Dependent Protein

Mutations in the CNGA3 gene, which encodes the A subunit of the cyclic guanosine monophosphate (cGMP)-gated cation channel in cone photoreceptor outer segments, cause total colour blindness, also referred to as achromatopsia. Cones lacking this channel protein are non-functional, accumulate high levels of the second messenger cGMP and degenerate over time after induction of ER stress. The cell death mechanisms that lead to loss of affected cones are only partially understood. Here, we explored the disease mechanisms in the Cnga3 knockout (KO) mouse model of achromatopsia. We found that another important effector of cGMP, the cGMP-dependent protein kinase 2 (Prkg2) is crucially involved in cGMP cytotoxicity of cones in Cnga3 KO mice. Virus-mediated knockdown or genetic ablation of Prkg2 in Cnga3 KO mice counteracted degeneration and preserved the number of cones. Analysis of markers of endoplasmic reticulum stress and unfolded protein response confirmed that induction of these processes in Cnga3 KO cones also depends on Prkg2. In conclusion, we identified Prkg2 as a novel key mediator of cone photoreceptor degeneration in achromatopsia. Our data suggest that this cGMP mediator could be a novel pharmacological target for future neuroprotective therapies.

A Mouse Model for Studying Cone Photoreceptor Pathologies

2014 ◽  
Vol 55 (8) ◽  
pp. 5304 ◽  
Author(s):  
Marijana Samardzija ◽  
Christian Caprara ◽  
Severin R. Heynen ◽  
Sarah Willcox DeParis ◽  
Isabelle Meneau ◽  
...  
Keyword(s):  
Mouse Model ◽  
Cone Photoreceptor

scholarly journals Retinoic acid signaling mediates peripheral cone photoreceptor survival in a mouse model of retina degeneration

2021 ◽  
Author(s):  
Ryoji Amamoto ◽  
Grace K Wallick ◽  
Constance Cepko
Keyword(s):  
Retinoic Acid ◽  
Mouse Model ◽  
Color Vision ◽  
Mouse Models ◽  
Night Vision ◽  
Conditional Knockout ◽  
Peripheral Retina ◽  
Rod Photoreceptor ◽  
Cone Photoreceptor

Retinitis Pigmentosa (RP) is a wide array of progressive, debilitating visual disorders caused by mutations in a diverse set of genes. In both human patients and mouse models of RP, rod photoreceptor dysfunction leads to loss of night vision, and is followed by secondary cone photoreceptor dysfunction and degeneration, leading to loss of daylight color vision. A strategy to prevent secondary cone death could provide a generalized RP therapy to preserve daylight color vision regardless of the underlying mutation. In mouse models of RP, cones in the far peripheral retina survive long-term, despite complete rod loss. The mechanism for such peripheral cone survival had not been explored. Here, we found that active retinoic acid (RA) signaling in peripheral Muller glia is both sufficient and necessary for the extended cone survival. RA depletion by conditional knockout of RA synthesis enzymes, or overexpression of an RA degradation enzyme, abrogated peripheral cone survival. Conversely, constitutive activation of RA signaling in the central retina promoted long-term cone survival. These results indicate that RA signaling mediates the prolonged peripheral cone survival in the rd1 mouse model of retinal degeneration, and provide a basis for a generic strategy for cone survival in the many diseases that lead to loss of cone-mediated vision.

scholarly journals Analysis of Early Cone Dysfunction in an In Vivo Model of Rod-Cone Dystrophy

2020 ◽  
Vol 21 (17) ◽  
pp. 6055 ◽  
Author(s):  
Mark Hassall ◽  
Michelle McClements ◽  
Alun Barnard ◽  
Maria Patrício ◽  
Sher Aslam ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Photoreceptor Cells ◽  
Cell Loss ◽  
Cone Dystrophy ◽  
Cone Photoreceptor ◽  
Cone Cell ◽  
Secondary Degeneration ◽  
Cone Dysfunction ◽  
Cone Function

Retinitis pigmentosa (RP) is a generic term for a group of genetic diseases characterized by loss of rod and cone photoreceptor cells. Although the genetic causes of RP frequently only affect the rod photoreceptor cells, cone photoreceptors become stressed in the absence of rods and undergo a secondary degeneration. Changes in the gene expression profile of cone photoreceptor cells are likely to occur prior to observable physiological changes. To this end, we sought to achieve greater understanding of the changes in cone photoreceptor cells early in the degeneration process of the Rho−/− mouse model. To account for gene expression changes attributed to loss of cone photoreceptor cells, we normalized PCR in the remaining number of cones to a cone cell reporter (OPN1-GFP). Gene expression profiles of key components involved in the cone phototransduction cascade were correlated with tests of retinal cone function prior to cell loss. A significant downregulation of the photoreceptor transcription factor Crx was observed, which preceded a significant downregulation in cone opsin transcripts that coincided with declining cone function. Our data add to the growing understanding of molecular changes that occur prior to cone dysfunction in a model of rod-cone dystrophy. It is of interest that gene supplementation of CRX by adeno-associated viral vector delivery prior to cone cell loss did not prevent cone photoreceptor degeneration in this mouse model.

scholarly journals Therapeutic silencing of SMOC2 prevents kidney function loss in mouse model of chronic kidney disease

iScience ◽  
2021 ◽  
pp. 103193
Author(s):  
Cuiyan Xin ◽  
Jiahui Lei ◽  
Qian Wang ◽  
Yixia Yin ◽  
Xiaoqian Yang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Mouse Model ◽  
Kidney Function ◽  
Function Loss

scholarly journals DNA-Encoded Library-Derived DDR1 Inhibitor Prevents Fibrosis and Renal Function Loss in a Genetic Mouse Model of Alport Syndrome

2018 ◽  
Vol 14 (1) ◽  
pp. 37-49 ◽  
Author(s):  
Hans Richter ◽  
Alexander L. Satz ◽  
Marc Bedoucha ◽  
Bernd Buettelmann ◽  
Ann C. Petersen ◽  
...  
Keyword(s):  
Renal Function ◽  
Mouse Model ◽  
Alport Syndrome ◽  
Genetic Mouse Model ◽  
Function Loss

scholarly journals C1q enhances cone photoreceptor survival in a mouse model of autosomal recessive retinitis pigmentosa

2011 ◽  
Vol 20 (1) ◽  
pp. 64-68 ◽  
Author(s):  
Marian M Humphries ◽  
Paul F Kenna ◽  
Matthew Campbell ◽  
Lawrence C S Tam ◽  
Anh T H Nguyen ◽  
...  
Keyword(s):  
Mouse Model ◽  
Retinitis Pigmentosa ◽  
Autosomal Recessive ◽  
Cone Photoreceptor

scholarly journals Restoration of Cone Vision in the CNGA3−/− Mouse Model of Congenital Complete Lack of Cone Photoreceptor Function

2010 ◽  
Vol 18 (12) ◽  
pp. 2057-2063 ◽  
Author(s):  
Stylianos Michalakis ◽  
Regine Mühlfriedel ◽  
Naoyuki Tanimoto ◽  
Vidhyasankar Krishnamoorthy ◽  
Susanne Koch ◽  
...  
Keyword(s):  
Mouse Model ◽  
Cone Photoreceptor

scholarly journals Iron-Chelating Drugs Enhance Cone Photoreceptor Survival in a Mouse Model of Retinitis Pigmentosa

2017 ◽  
Vol 58 (12) ◽  
pp. 5287 ◽  
Author(s):  
Ke Wang ◽  
Bo Peng ◽  
Jia Xiao ◽  
Orly Weinreb ◽  
Moussa B. H. Youdim ◽  
...  
Keyword(s):  
Mouse Model ◽  
Retinitis Pigmentosa ◽  
Cone Photoreceptor
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