Christina Zeitz , Jérome E. Roger , Isabelle Audo , Christelle Michiels , Nuria Sánchez-Farías , Juliette Varin , Helen Frederiksen , Baptiste Wilmet , Jacques Callebert , Marie-Laure Gimenez , Nassima Bouzidi , Frederic Blond , Xavier Guilllonneau , Stéphane Fouquet , Thierry Léveillard , Vasily Smirnov , Ajoy Vincent , Elise Héon , José-Alain Sahel , Barbara Kloeckener-Gruissem , Serge Picaud
{"title":"Shedding light on myopia by studying complete congenital stationary night blindness","authors":"Christina Zeitz , Jérome E. Roger , Isabelle Audo , Christelle Michiels , Nuria Sánchez-Farías , Juliette Varin , Helen Frederiksen , Baptiste Wilmet , Jacques Callebert , Marie-Laure Gimenez , Nassima Bouzidi , Frederic Blond , Xavier Guilllonneau , Stéphane Fouquet , Thierry Léveillard , Vasily Smirnov , Ajoy Vincent , Elise Héon , José-Alain Sahel , Barbara Kloeckener-Gruissem , Serge Picaud","doi":"10.1016/j.preteyeres.2022.101155","DOIUrl":null,"url":null,"abstract":"<div><p><span><span><span>Myopia is the most common eye disorder, caused by heterogeneous genetic and </span>environmental factors<span><span><span>. Rare progressive and stationary inherited retinal disorders are often associated with high myopia. Genes implicated in myopia encode proteins involved in a variety of </span>biological processes<span> including eye morphogenesis, </span></span>extracellular matrix organization, visual perception, circadian rhythms, and retinal signaling. Differentially expressed genes (DEGs) identified in animal models mimicking myopia are helpful in suggesting candidate genes implicated in human myopia. Complete </span></span>congenital stationary night blindness<span><span> (cCSNB) in humans and animal models represents an ON-bipolar cell signal transmission defect and is also associated with high myopia. Thus, it represents also an interesting model to identify myopia-related genes, as well as disease mechanisms. While the origin of </span>night blindness<span> is molecularly well established, further research is needed to elucidate the mechanisms of myopia development in subjects with cCSNB. Using whole transcriptome analysis on three different mouse models of cCSNB (in </span></span></span><em>Gpr179</em><sup>−/−</sup>, <em>Lrit3</em><sup>−/−</sup> and <em>Grm6</em><sup>−/−</sup><span>), we identified novel actors of the retinal signaling cascade, which are also novel candidate genes for myopia. Meta-analysis of our transcriptomic<span> data with published transcriptomic databases and genome-wide association studies from myopia cases led us to propose new biological/cellular processes/mechanisms potentially at the origin of myopia in cCSNB subjects. The results provide a foundation to guide the development of pharmacological myopia therapies.</span></span></p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":null,"pages":null},"PeriodicalIF":18.6000,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Progress in Retinal and Eye Research","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S135094622200115X","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Myopia is the most common eye disorder, caused by heterogeneous genetic and environmental factors. Rare progressive and stationary inherited retinal disorders are often associated with high myopia. Genes implicated in myopia encode proteins involved in a variety of biological processes including eye morphogenesis, extracellular matrix organization, visual perception, circadian rhythms, and retinal signaling. Differentially expressed genes (DEGs) identified in animal models mimicking myopia are helpful in suggesting candidate genes implicated in human myopia. Complete congenital stationary night blindness (cCSNB) in humans and animal models represents an ON-bipolar cell signal transmission defect and is also associated with high myopia. Thus, it represents also an interesting model to identify myopia-related genes, as well as disease mechanisms. While the origin of night blindness is molecularly well established, further research is needed to elucidate the mechanisms of myopia development in subjects with cCSNB. Using whole transcriptome analysis on three different mouse models of cCSNB (in Gpr179−/−, Lrit3−/− and Grm6−/−), we identified novel actors of the retinal signaling cascade, which are also novel candidate genes for myopia. Meta-analysis of our transcriptomic data with published transcriptomic databases and genome-wide association studies from myopia cases led us to propose new biological/cellular processes/mechanisms potentially at the origin of myopia in cCSNB subjects. The results provide a foundation to guide the development of pharmacological myopia therapies.
期刊介绍:
Progress in Retinal and Eye Research is a Reviews-only journal. By invitation, leading experts write on basic and clinical aspects of the eye in a style appealing to molecular biologists, neuroscientists and physiologists, as well as to vision researchers and ophthalmologists.
The journal covers all aspects of eye research, including topics pertaining to the retina and pigment epithelial layer, cornea, tears, lacrimal glands, aqueous humour, iris, ciliary body, trabeculum, lens, vitreous humour and diseases such as dry-eye, inflammation, keratoconus, corneal dystrophy, glaucoma and cataract.