Structural and Functional Phenotyping in the Cone-Specific Photoreceptor Function Loss 1 (cpfl1) Mouse Mutant – A Model of Cone Dystrophies

Fischer, Manuel; Tanimoto, Naoyuki; Beck, Susanne; Huber, Günter L.; Schaeferhoff, Karin; Michalakis, Stylianos; Rieß, Olaf; Wissinger, Bernd; Biel, Martin; Bonin, Michael; Seeliger, Mathias W.

doi:10.1007/978-1-4419-1399-9_68

Cited by 8 publications

(5 citation statements)

References 7 publications

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“…RCD is especially debilitating to vision in human patients. However, there are few animal models of cone dystrophy [9–11]. Our laboratory has discovered and bred CSNB and RCD rat models to prove X-linked recessive inheritance.…”

Section: Introductionmentioning

confidence: 99%

Properties of Flicker ERGs in Rat Models with Retinal Degeneration

Guo

et al. 2012

ISRN Ophthalmology

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Purpose. To describe the characteristics of rod and cone functions in rat models for congenital stationary night blindness (CSNB) and retinal cone dysfunction (RCD). Methods. Rod and cone function were isolated by recording the rod-/cone-driven flicker and blue light flicker electroretinograms (ERGs). Results. During dark adaptation, the amplitudes of flicker ERGs in CSNB rats were lower than those in control rats; the responses of RCD rats were similar to control rats. During light adaptation, the amplitudes of flicker ERGs in CSNB rats were reduced; whereas the responses of RCD rats were not detected. Blue flicker ERGs were not observed in CSNB rats at lower frequencies. The cone driven critical flicker frequencies (CFFs) in control rats were 62 Hz. The rod driven CFF of RCD rats was 20 Hz; whereas the rod-/cone-driven CFF of CSNB rats both were about 25 Hz. Conclusions. The function of the rod system was damaged completely, the cones were the source of vision in CSNB rats. Rod system function is excellent in RCD rat. The rods of albinism rats are sensitive to frequencies less than 20 Hz; whereas the cones are sensitive to frequencies up to 62 Hz.

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Section: Introductionmentioning

confidence: 99%

Properties of Flicker ERGs in Rat Models with Retinal Degeneration

Guo

et al. 2012

ISRN Ophthalmology

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“…Comparative analysis of three ACHM mouse models shows that they have a similar progression of cone death, with a sharp peak at roughly the same time around postnatal day 24 (P24) (Michalakis et al 2005;Ding et al 2009;Trifunovic et al 2010), but a continual degeneration was also reported in both the cpfl1 (Fischer et al 2010) and Cnga3…”

Section: Pde6 Deficiency and Cone Cell Death Mechanismsmentioning

confidence: 93%

“…Despite the controversy surrounding cone fate in human patients, in the last few years several ACHM animal models have been described and shown to have active cone degeneration: the Cnga3 naturally-occurring mutant (Pang et al 2010) and knockout mouse models ( Cnga3 -/-) (Biel et al 1999), the Pde6c-deficient cpfl1 mouse and zebrafish models (Stearns et al 2007;Chang et al 2009) and the dog and mouse model of Cngb3 deficiency (Sidjanin et al 2002;Ding et al 2009). Even though the progressive loss of cone photoreceptors was established in several of these models (Michalakis et al 2005;Ding et al 2009;Fischer et al 2010;Trifunovic et al 2010;Xu et al 2011), the precise kinetics of the degeneration has not yet been fully elucidated.…”

Section: Primary Cone Loss In Achromatopsiamentioning

confidence: 98%

Understanding Cone Photoreceptor Cell Death in Achromatopsia

Carvalho

Vandenberghe

2015

Retinal Degenerative Diseases

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Colour vision is only achieved in the presence of healthy and functional cone photoreceptors found in the retina. It is an essential component of human vision and usually the first complaint patients undergoing vision degeneration have is the loss of daylight colour vision. Therefore, an understanding of the biology and basic mechanisms behind cone death under the degenerative state of retinal dystrophies and how the activation of the apoptotic pathway is triggered will provide valuable knowledge. It will also have broader applications for a spectrum of visual disorders and will be critical for future advances in translational research.

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“…The Cpfl1 [cone photoreceptor function loss (1)] mouse harbors a 116-bp insertion between exon 4 and 5, as well as an additional 1-bp deletion in exon 7 in the Pde6c gene, leading to an in-frame shift, introducing premature termination codons, the loss of activity of the enzyme, and the accumulation of cGMP [49,88,98]. Cpfl1 mice display the early-onset, rapid/severe cone degeneration phenotype, including the loss of cone function and death of cones [88,[98][99][100].…”

Section: Deficiency Of Pde6mentioning

confidence: 99%

cGMP Signaling in Photoreceptor Degeneration

Yang

et al. 2023

IJMS

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Photoreceptors in the retina are highly specialized neurons with photosensitive molecules in the outer segment that transform light into chemical and electrical signals, and these signals are ultimately relayed to the visual cortex in the brain to form vision. Photoreceptors are composed of rods and cones. Rods are responsible for dim light vision, whereas cones are responsible for bright light, color vision, and visual acuity. Photoreceptors undergo progressive degeneration over time in many hereditary and age-related retinal diseases. Despite the remarkable heterogeneity of disease-causing genes, environmental factors, and pathogenesis, the progressive death of rod and cone photoreceptors ultimately leads to loss of vision/blindness. There are currently no treatments available for retinal degeneration. Cyclic guanosine 3′, 5′-monophosphate (cGMP) plays a pivotal role in phototransduction. cGMP governs the cyclic nucleotide-gated (CNG) channels on the plasma membrane of the photoreceptor outer segments, thereby regulating membrane potential and signal transmission. By gating the CNG channels, cGMP regulates cellular Ca2+ homeostasis and signal transduction. As a second messenger, cGMP activates the cGMP-dependent protein kinase G (PKG), which regulates numerous targets/cellular events. The dysregulation of cGMP signaling is observed in varieties of photoreceptor/retinal degenerative diseases. Abnormally elevated cGMP signaling interferes with various cellular events, which ultimately leads to photoreceptor degeneration. In line with this, strategies to reduce cellular cGMP signaling result in photoreceptor protection in mouse models of retinal degeneration. The potential mechanisms underlying cGMP signaling-induced photoreceptor degeneration involve the activation of PKG and impaired Ca2+ homeostasis/Ca2+ overload, resulting from overactivation of the CNG channels, as well as the subsequent activation of the downstream cellular stress/death pathways. Thus, targeting the cellular cGMP/PKG signaling and the Ca2+-regulating pathways represents a significant strategy for photoreceptor protection in retinal degenerative diseases.

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Structural and Functional Phenotyping in the Cone-Specific Photoreceptor Function Loss 1 (cpfl1) Mouse Mutant – A Model of Cone Dystrophies

Cited by 8 publications

References 7 publications

Properties of Flicker ERGs in Rat Models with Retinal Degeneration

Properties of Flicker ERGs in Rat Models with Retinal Degeneration

Understanding Cone Photoreceptor Cell Death in Achromatopsia

cGMP Signaling in Photoreceptor Degeneration

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