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

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 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.

In vivo potency testing of subretinal rAAV5.hCNGB1 gene therapy in the Cngb1 knockout mouse model of retinitis pigmentosa

2021 ◽  
Author(s):  
Johanna E Wagner ◽  
Lena Zobel ◽  
Maximilian Joachim Gerhardt ◽  
Catherine R O'Riordan ◽  
Amy Frederick ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Mouse Model ◽  
Retinitis Pigmentosa ◽  
Knockout Mouse ◽  
Knockout Mouse Model

scholarly journals Attenuation of Vision Loss and Delay in Apoptosis of Photoreceptors Induced by Proinsulin in a Mouse Model of Retinitis Pigmentosa

2008 ◽  
Vol 49 (9) ◽  
pp. 4188 ◽  
Author(s):  
Silvia Corrochano ◽  
Rima Barhoum ◽  
Patricia Boya ◽  
Ana I. Arroba ◽  
Natalia Rodri´guez-Muela ◽  
...  
Keyword(s):  
Mouse Model ◽  
Retinitis Pigmentosa ◽  
Vision Loss

Electrostimulation in an autonomous culture lab-on-chip provides neuroprotection of a retinal explant from a retinitis pigmentosa mouse-model

2019 ◽  
Vol 288 ◽  
pp. 337-346 ◽  
Author(s):  
Miguel Cabello ◽  
Marta Mozo ◽  
Berta De la Cerda ◽  
Carmen Aracil ◽  
Francisco J. Diaz-Corrales ◽  
...  
Keyword(s):  
Mouse Model ◽  
Retinitis Pigmentosa ◽  
Lab On Chip ◽  
On Chip

scholarly journals Targeting of the NRL Pathway as a Therapeutic Strategy to Treat Retinitis Pigmentosa

2020 ◽  
Vol 9 (7) ◽  
pp. 2224 ◽  
Author(s):  
Spencer M. Moore ◽  
Dorota Skowronska-Krawczyk ◽  
Daniel L. Chao
Keyword(s):  
Retinitis Pigmentosa ◽  
Autosomal Recessive ◽  
Therapeutic Strategy ◽  
Leucine Zipper ◽  
Retinal Dystrophy ◽  
Rod Photoreceptor ◽  
Cone Photoreceptor ◽  
Future Directions ◽  
Inherited Retinal Dystrophy ◽  
Visual Acuity Loss

Retinitis pigmentosa (RP) is an inherited retinal dystrophy (IRD) with a prevalence of 1:4000, characterized by initial rod photoreceptor loss and subsequent cone photoreceptor loss with accompanying nyctalopia, visual field deficits, and visual acuity loss. A diversity of causative mutations have been described with autosomal dominant, autosomal recessive, and X-linked inheritance and sporadic mutations. The diversity of mutations makes gene therapy challenging, highlighting the need for mutation-agnostic treatments. Neural leucine zipper (NRL) and NR2E3 are factors important for rod photoreceptor cell differentiation and homeostasis. Germline mutations in NRL or NR2E3 leads to a loss of rods and an increased number of cones with short wavelength opsin in both rodents and humans. Multiple groups have demonstrated that inhibition of NRL or NR2E3 activity in the mature retina could endow rods with certain properties of cones, which prevents cell death in multiple rodent RP models with diverse mutations. In this review, we summarize the literature on NRL and NR2E3, therapeutic strategies of NRL/NR2E3 modulation in preclinical RP models, as well as future directions of research. In summary, inhibition of the NRL/NR2E3 pathway represents an intriguing mutation agnostic and disease-modifying target for the treatment of RP.

scholarly journals Mechanisms of Photoreceptor Death in Retinitis Pigmentosa

Genes ◽  
2020 ◽  
Vol 11 (10) ◽  
pp. 1120
Author(s):  
Fay Newton ◽  
Roly Megaw
Keyword(s):  
Retinitis Pigmentosa ◽  
Apoptotic Cell ◽  
Gene Replacement ◽  
Innate Immune ◽  
Cone Photoreceptor ◽  
Cell Death Pathways ◽  
Retinal Photoreceptors ◽  
Photoreceptor Death ◽  
Made In

Retinitis pigmentosa (RP) is the most common cause of inherited blindness and is characterised by the progressive loss of retinal photoreceptors. However, RP is a highly heterogeneous disease and, while much progress has been made in developing gene replacement and gene editing treatments for RP, it is also necessary to develop treatments that are applicable to all causative mutations. Further understanding of the mechanisms leading to photoreceptor death is essential for the development of these treatments. Recent work has therefore focused on the role of apoptotic and non-apoptotic cell death pathways in RP and the various mechanisms that trigger these pathways in degenerating photoreceptors. In particular, several recent studies have begun to elucidate the role of microglia and innate immune response in the progression of RP. Here, we discuss some of the recent progress in understanding mechanisms of rod and cone photoreceptor death in RP and summarise recent clinical trials targeting these pathways.

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
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