A New<i>Fgf10</i>Mutation in the Mouse Leads to Atrophy of the Harderian Gland and Slit-Eye Phenotype in Heterozygotes: A Novel Model for Dry-Eye Disease?

Puk, Oliver; Espósito, Irene; Söker, Torben; Löster, Jana; Budde, Birgit; Nürnberg, Peter; Michel-Soewarto, Dian; Fuchs, Helmut; Wolf, Eckhard; Angelis, Martin Hrabé de; Graw, Jochen

doi:10.1167/iovs.09-3451

Cited by 14 publications

(11 citation statements)

References 32 publications

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“…Furthermore, defect in FGF10 leads to the development and differentiation of several ocular tissues. [26][27][28] In our previous study of microRNA-328, retinoic acid, and TGF-b were shown to be involved in the same network regulation leading to the development of myopia.29 A recent study indicated that retinoic acid could regulate the TGFb pathway in the control of FGF10 expression.30 Therefore, the present study focuses on the involvement of FGF10 in the development of myopia.The present study aims to discover the role of FGF10 in myopia by the following methods: (1) measuring the FGF10 expression during the development of myopia in mice, (2) testing for the association between single nucleotide polymorphisms (SNPs) of FGF10 and high myopia in a Chinese cohort residing in Taiwan, and (3) evaluating the possible biologic consequence of the associated SNP. …”

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confidence: 99%

A Functional Polymorphism at the FGF10 Gene Is Associated With Extreme Myopia

Hsi

Chen

Chang

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Fibroblast growth factor-10 (FGF10) can modulate extracellular matrix associated genes and, therefore, it could be a myopia susceptibility gene. This study used an animal model, single nucleotide polymorphisms (SNPs) association, and genetic functional assay to evaluate FGF10 gene for myopia. METHODS.The expression levels of FGF10 gene were compared among the form deprivation myopic (FDM) eyes, the fellow eyes of the FDM group, and the healthy eyes of experimental mice. In the present study 1020 cases ( À6.0 diopters [D]) and 960 controls ( ‡À1.5 D) were enrolled from a Chinese population. Eight tagging SNPs were genotyped to test for an association between genotypes and myopia. The luciferase reporter assay was conducted for the particular SNP to assess the allelic effect on gene expression. RESULTS.The sclera of FDM eyes had a 2.57-fold higher level of FGF10 mRNA (P ¼ 0.018) than the fellow eyes. Although no SNP was associated with high myopia, SNP rs339501 was significantly associated with extreme myopia ( À10 D, P ¼ 0.008) and the odds ratio (OR) was 1.58 for G allele carriers. The luciferase assay showed that the risk G allele significantly caused a higher expression level than the A allele (P ¼ 0.011).CONCLUSIONS. The evidence suggested FGF10 to be a risk factor for myopia. The sclera of myopic eyes had higher FGF10 levels. The risk G allele of SNP rs339501 was associated with extreme myopia in human and caused a higher gene expression in the luciferase assay. It is concluded that the FGF10 could have been involved in the development of myopia.Keywords: FDM, myopia, FGF10 M yopia is a common eye condition worldwide, and its prevalence varies widely among populations and ages and between the sexes.1-3 When the definition of less than À6 diopters (D) was used, the prevalence of high myopia was found to be 18% among young Taiwanese men and 24% among young Taiwanese women 1 ; both of which are higher than the 13.1% reported among young men in Singapore.2 Furthermore, an increased frequency of high myopia (<À6.0 D) was found in young Taiwanese people: 10.9% in 1983 and 21% in 2000. 4 Myopia progresses quickly in childhood, especially around the teenage years. By early adulthood, the rate of change in ocular refraction tends to decline and the prevalence of myopia stabilizes. 5 Several studies have also shown the family history of myopia to be a significant risk factor. 6,7 Recently, genetic association studies including genome-wide association studies (GWAS) have reported several susceptibility genes to nonsyndromic myopia. 8-17Scleral remodeling is one of the important mechanisms for the development of myopia, 18 Several genes are associated with the scleral remodeling including sulfated glycosaminoglycans (GAGs), 19 matrix metalloproteinases (MMPs), 20 tissue inhibitors of metalloproteinases (TIMPs), 20 and TGF-b. 21 The expression of fibroblast growth factor 10 (FGF10) has been shown to be abundant in the murine retina and sclera. 22,23 FGF10 plays a pivotal role in controlling elongation of lacrima...

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confidence: 99%

A Functional Polymorphism at the FGF10 Gene Is Associated With Extreme Myopia

Hsi

Chen

Chang

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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“…32 Such traits as eyeball volume recovered by the proposed method can also help researchers and clinicians better understand eye growth patterns under certain disease conditions, [47][48][49][50] the mechanisms vision systems follow to maintain visual clarity, 51,52 and key genes affecting visual pathways. [53][54][55][56][57][58] Although the proposed method enables estimation of a 3D eyeball structure from the corresponding 2D flatmount image, it can be further improved in the following ways in the future. (1) The dissection process might be improved by etching or partially eroding the sclera to relax the tissue to reduce wrinkling or bulging.…”

Section: Discussionmentioning

confidence: 99%

Computational Model-Based Estimation of Mouse Eyeball Structure From Two-Dimensional Flatmount Microscopy Images

Kim

et al. 2021

Trans. Vis. Sci. Tech.

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“…There are few reports about eyelid function and eye accessory organs in adult EOB mice, because many studies have been focused on eyelid development at various embryonic stages. A previous study reported that shrinkage of the harderian gland in Fgf10 mutant mice could lead to corneal disease, due to defects in eyeball wetting (Puk et al, 2009). In conclusion, studies on eyelid function in EOB models would promote early diagnosis, prevention, and therapy for human heredity congenital eye disease, and development of relevant drugs.…”

Section: Gene Namementioning

confidence: 99%

Defective eyelid leading edge cell migration in C57BL/6-corneal opacity mice with an “eye open at birth” phenotype

Liu

Jiang

et al. 2016

Genet. Mol. Res.

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A NewFgf10Mutation in the Mouse Leads to Atrophy of the Harderian Gland and Slit-Eye Phenotype in Heterozygotes: A Novel Model for Dry-Eye Disease?

Abstract: The mutation in the Fgf10 gene leads to a dominant slit-eye phenotype caused by atrophy of the Harderian gland.

Cited by 14 publications

References 32 publications

A Functional Polymorphism at the FGF10 Gene Is Associated With Extreme Myopia

A Functional Polymorphism at the FGF10 Gene Is Associated With Extreme Myopia

Computational Model-Based Estimation of Mouse Eyeball Structure From Two-Dimensional Flatmount Microscopy Images

Defective eyelid leading edge cell migration in C57BL/6-corneal opacity mice with an “eye open at birth” phenotype

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