Naturally-occurring myopia and loss of cone function in a sheep model of achromatopsia

Ross, Maya; Ofri, Ron; Aizenberg, Itzhak; Abu-Siam, Mazen; Pe’er, Oren; Arad, Dikla; Rosov, Alexander; Gootwine, E.; Dvir, Hay; Honig, Hen; Obolensky, Alexey; Averbukh, Edward; Banin, Eyal; Gantz, Liat

doi:10.1038/s41598-020-76205-z

Cited by 13 publications

(8 citation statements)

References 79 publications

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“…Cases of cone dystrophy, cone-rod dystrophy and color vision defect caused by OPN1LW/OPN1MW mutation could had different levels of myopia manifestation [23]. Ross et al demonstrated that loss of cone function causes naturally-occurring myopia in sheep [24] and on this basis we hypothesize that ARR3 cause myopia through functional changes in cones.…”

Section: Discussionmentioning

confidence: 71%

The causal mutation in ARR3 gene for high myopia and progressive color vision defect

Cong

Ning

et al. 2022

Preprint

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The ARR3 gene, also known as cone arrestin, belongs to the arrestin family and is expressed in cone cells, inactivating phosphorated-opsins and preventing cone signals. Variants of ARR3 reportedly cause X-linked dominant female-limited early-onset (age < 7 years old) high myopia (<-6D). Here, we reveal a new mutation (c.228T>A, p.Tyr76*) in ARR3 gene that can cause early-onset high myopia (eoHM) limited in female carriers, and protan/deutan color vision defect affecting both genders. Using ten years of clinical follow-up data, we identified gradually worsen cone dysfunction/color vision as a key feature among affected individuals. We present a hypothesis of unbalanced color-vision signal output that had lowered blue color contribution from cone cells could potentially explain the etiology of this disease.

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Section: Discussionmentioning

confidence: 71%

The causal mutation in ARR3 gene for high myopia and progressive color vision defect

Cong

Ning

et al. 2022

Preprint

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“…In domestic animals, to this point in sheep [11][12][13] and dogs [19][20][21][22] (previously reported as cone degeneration and canine hemeralopia), the underlying genetics of different forms of achromatopsia are reported. Cones alone are affected in Alaskan Malamute (OMIA 001365-9615) and the German shorthaired pointers (OMIA 001676-9615) because of breed specific mutations in CNGB3, a cone-specific gene.…”

Section: Discussionmentioning

confidence: 93%

“…In sheep, a form of CNGA3-related achromatopsia has been characterized (OMIA 001481-9940) [11]. This ovine condition was intensively used for functional restoration of cone function [12], highlighting the biomedical value of such large animal models [13,14] in addition to the direct benefits for animal breeding and animal health.…”

Section: Introductionmentioning

confidence: 99%

CNGB3 Missense Variant Causes Recessive Achromatopsia in Original Braunvieh Cattle

Häfliger

Marchionatti

Michele

et al. 2021

IJMS

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Sporadic occurrence of inherited eye disorders has been reported in cattle but so far pathogenic variants were found only for rare forms of cataract but not for retinopathies. The aim of this study was to characterize the phenotype and the genetic aetiology of a recessive form of congenital day-blindness observed in several cases of purebred Original Braunvieh cattle. Electroretinography in an affected calf revealed absent cone-mediated function, whereas the rods continue to function normally. Brain areas involved in vision were morphologically normal. When targeting cones by immunofluorescence, a decrease in cone number and an accumulation of beta subunits of cone cyclic-nucleotide gated channel (CNGB3) in the outer plexiform layer of affected animals was obvious. Achromatopsia is a monogenic Mendelian disease characterized by the loss of cone photoreceptor function resulting in day-blindness, total color-blindness, and decreased central visual acuity. After SNP genotyping and subsequent homozygosity mapping with twelve affected cattle, we performed whole-genome sequencing and variant calling of three cases. We identified a single missense variant in the bovine CNGB3 gene situated in a ~2.5 Mb homozygous genome region on chromosome 14 shared between all cases. All affected cattle were homozygous carriers of the p.Asp251Asn mutation that was predicted to be deleterious, affecting an evolutionary conserved residue. In conclusion, we have evidence for the occurrence of a breed-specific novel CNGB3-related form of recessively inherited achromatopsia in Original Braunvieh cattle which we have designated OH1 showing an allele frequency of the deleterious allele of ~8%. The identification of carriers will enable selection against this inherited disorder. The studied cattle might serve as an animal model to further elucidate the function of CNGB3 in mammals.

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“…Achromatopsia is an inherited retinal disease characterized by early loss of cone photoreceptors and later rod photoreceptor loss 31 , 138 , 139 . In a zebrafish model of human achromatopsia ( pde6c w59 ), cone photoreceptors expressed high levels of RIPK1/3, whereas rod photoreceptors were immunopositive for caspase-3, indicating activation of apoptosis 31 .…”

Section: Necroptosis Drives Death Of Retinal Cells In Retinal Disease...mentioning

confidence: 99%

Targeting Necroptosis: A Novel Therapeutic Option for Retinal Degenerative Diseases

Zhang¹,

Hu²,

Zhao³

et al. 2023

Int. J. Biol. Sci.

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The discovery of the necroptosis, a form of regulated necrosis that is mediated by receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed-lineage kinase domain-like pseudokinase (MLKL), represents a major breakthrough that has dramatically altered the conception of necrosis -traditionally thought of as uncontrolled cell death -in various human diseases. Retinal cell death is a leading cause of blindness and has been identified in most retinal diseases, e.g., age-related macular degeneration, glaucoma, retinal detachment, retinitis pigmentosa, etc. Increasing evidence demonstrates that retinal degenerative diseases also share a common mechanism in necroptosis. Exacerbated necroptotic cell death hinders the treatment for retinal degenerative diseases. In this review, we highlight recent advances in identifying retinal necroptosis, summarize the underlying mechanisms of necroptosis in retinal degenerative diseases, and discuss potential anti-necroptosis strategies, such as selective inhibitors and chemical agents, for treating retinal degenerative diseases.

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Naturally-occurring myopia and loss of cone function in a sheep model of achromatopsia

Cited by 13 publications

References 79 publications

The causal mutation in ARR3 gene for high myopia and progressive color vision defect

The causal mutation in ARR3 gene for high myopia and progressive color vision defect

CNGB3 Missense Variant Causes Recessive Achromatopsia in Original Braunvieh Cattle

Targeting Necroptosis: A Novel Therapeutic Option for Retinal Degenerative Diseases

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