cGMP-dependent cone photoreceptor degeneration in the cpfl1 mouse retina

2010 ◽  
Vol 518 (17) ◽  
pp. 3604-3617 ◽  
Author(s):  
Dragana Trifunović ◽  
Katja Dengler ◽  
Stylianos Michalakis ◽  
Eberhart Zrenner ◽  
Bernd Wissinger ◽  
...  
Keyword(s):  
Mouse Retina ◽  
Cone Photoreceptor ◽  
Photoreceptor Degeneration

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.

scholarly journals A QTL on Chromosome 10 Modulates Cone Photoreceptor Number in the Mouse Retina

2011 ◽  
Vol 52 (6) ◽  
pp. 3228 ◽  
Author(s):  
Irene E. Whitney ◽  
Mary A. Raven ◽  
Lu Lu ◽  
Robert W. Williams ◽  
Benjamin E. Reese
Keyword(s):  
Mouse Retina ◽  
Cone Photoreceptor ◽  
Chromosome 10

scholarly journals Disease sequence from mutant rhodopsin allele to rod and cone photoreceptor degeneration in man

1998 ◽  
Vol 95 (12) ◽  
pp. 7103-7108 ◽  
Author(s):  
A. V. Cideciyan ◽  
D. C. Hood ◽  
Y. Huang ◽  
E. Banin ◽  
Z.-Y. Li ◽  
...  
Keyword(s):  
Cone Photoreceptor ◽  
Photoreceptor Degeneration

scholarly journals Berberine protects against light-induced photoreceptor degeneration in the mouse retina

2016 ◽  
Vol 145 ◽  
pp. 1-9 ◽  
Author(s):  
Delu Song ◽  
Jiantao Song ◽  
Chenguang Wang ◽  
Yafeng Li ◽  
Joshua L. Dunaief
Keyword(s):  
Mouse Retina ◽  
Photoreceptor Degeneration

scholarly journals Cone Photoreceptor Degeneration and Neuroinflammation in the Zebrafish Bardet-Biedl Syndrome 2 (bbs2) Mutant Does Not Lead to Retinal Regeneration

2020 ◽  
Vol 8 ◽  
Author(s):  
Ping Song ◽  
Joseph Fogerty ◽  
Lauren T. Cianciolo ◽  
Rachel Stupay ◽  
Brian D. Perkins
Keyword(s):  
Cell Proliferation ◽  
Inflammatory Response ◽  
Retinal Degeneration ◽  
Autosomal Recessive Disorder ◽  
Müller Cell ◽  
Cone Photoreceptor ◽  
Photoreceptor Degeneration ◽  
Retinal Regeneration ◽  
Bardet Biedl Syndrome ◽  
Muller Cell

Bardet-Biedl syndrome (BBS) is a heterogeneous and pleiotropic autosomal recessive disorder characterized by obesity, retinal degeneration, polydactyly, renal dysfunction, and mental retardation. BBS results from defects in primary and sensory cilia. Mutations in 21 genes have been linked to BBS and proteins encoded by 8 of these genes form a multiprotein complex termed the BBSome. Mutations in BBS2, a component of the BBSome, result in BBS as well as non-syndromic retinal degeneration in humans and rod degeneration in mice, but the role of BBS2 in cone photoreceptor survival is not clear. We used zebrafish bbs2–/– mutants to better understand how loss of bbs2 leads to photoreceptor degeneration. Zebrafish bbs2–/– mutants exhibited impaired visual function as larvae and adult zebrafish underwent progressive cone photoreceptor degeneration. Cone degeneration was accompanied by increased numbers of activated microglia, indicating an inflammatory response. Zebrafish exhibit a robust ability to regenerate lost photoreceptors following retinal damage, yet cone degeneration and inflammation was insufficient to trigger robust Müller cell proliferation. In contrast, high intensity light damage stimulated Müller cell proliferation and photoreceptor regeneration in both wild-type and bbs2–/– mutants, although the bbs2–/– mutants could only restore cones to pre-damaged densities. In summary, these findings suggest that cone degeneration leads to an inflammatory response in the retina and that BBS2 is necessary for cone survival. The zebrafish bbs2 mutant also represents an ideal model to identify mechanisms that will enhance retinal regeneration in degenerating diseases.

Role of Heparin-Binding Epidermal Growth Factor–Like Growth Factor in Light-Induced Photoreceptor Degeneration in Mouse Retina

2013 ◽  
Vol 54 (6) ◽  
pp. 3815 ◽  
Author(s):  
Yuki Inoue ◽  
Kazuhiro Tsuruma ◽  
Tomohiro Nakanishi ◽  
Atsushi Oyagi ◽  
Yuta Ohno ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Mouse Retina ◽  
Heparin Binding ◽  
Photoreceptor Degeneration ◽  
Epidermal Growth

Systemic administration of a free radical scavenger, edaravone, protects against light-induced photoreceptor degeneration in the mouse retina

2010 ◽  
Vol 642 (1-3) ◽  
pp. 77-85 ◽  
Author(s):  
Shunsuke Imai ◽  
Yuta Inokuchi ◽  
Shinsuke Nakamura ◽  
Kazuhiro Tsuruma ◽  
Masamitsu Shimazawa ◽  
...  
Keyword(s):  
Free Radical ◽  
Free Radical Scavenger ◽  
Systemic Administration ◽  
Mouse Retina ◽  
Radical Scavenger ◽  
Photoreceptor Degeneration

scholarly journals Local signals in mouse horizontal cell dendrites

2017 ◽  
Author(s):  
Camille A. Chapot ◽  
Christian Behrens ◽  
Luke E. Rogerson ◽  
Tom Baden ◽  
Sinziana Pop ◽  
...  
Keyword(s):  
Glutamate Release ◽  
Horizontal Cell ◽  
Horizontal Cells ◽  
Single Type ◽  
Mouse Retina ◽  
Gabaergic Interneuron ◽  
List Type ◽  
Cone Photoreceptor ◽  
Cone Photoreceptors ◽  
Temporal Properties

SummaryThe mouse retina contains a single type of horizontal cell, a GABAergic interneuron that samples from all cone photoreceptors within reach and modulates their glutamatergic output via parallel feedback mechanisms. Because horizontal cells form an electrically-coupled network, they have been implicated in global signal processing, such as large scale contrast enhancement. Recently, it has been proposed that horizontal cells can also act locally at the level of individual cone photoreceptors. To test this possibility physiologically, we used two-photon microscopy to record light stimulus-evoked Ca2+signals in cone axon terminals and horizontal cell dendrites as well as glutamate release in the outer plexiform layer. By selectively stimulating the two mouse cone opsins with green and UV light, we assessed whether signals from individual cones remain “isolated” within horizontal cell dendritic tips, or whether they spread across the dendritic arbour. Consistent with the mouse‘s opsin expression gradient, we found that the Ca2+signals recorded from dendrites of dorsal horizontal cells were dominated by M- and those of ventral horizontal cells by S-opsin activation. The signals measured in neighbouring horizontal cell dendritic tips varied markedly in their chromatic preference, arguing against global processing. Rather, our experimental data and results from biophysically realistic modelling support the idea that horizontal cells can process cone input locally, extending the “classical” view of horizontal cells function. Pharmacologically removing horizontal cells from the circuitry reduced the sensitivity of the cone signal to low frequencies, suggesting that local horizontal cell feedback shapes the temporal properties of cone output.HighlightsLight-evoked Ca2+signals in horizontal cell dendrites reflect opsin gradientChromatic preferences in neighbouring dendritic tips vary markedlyMouse horizontal cells process cone photoreceptor input locallyLocal horizontal cell feedback shapes the temporal properties of cone outputeTOC BlurbChapot et al. show that local light responses in mouse horizontal cell dendrites inherit properties, including chromatic preference, from the presynaptic cone photoreceptor, suggesting that their dendrites can provide “private” feedback to cones, for instance, to shape the temporal filtering properties of the cone synapse.

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