Shedding light on myopia by studying complete congenital stationary night blindness. (March 2023)

• Record Type: Journal Article
• Authors: Zeitz, Christina; Roger, Jérome E.; Audo, Isabelle; Michiels, Christelle; Sánchez-Farías, Nuria; Varin, Juliette; Frederiksen, Helen; Wilmet, Baptiste; Callebert, Jacques; Gimenez, Marie-Laure; Bouzidi, Nassima; Blond, Frederic; Guilllonneau, Xavier; Fouquet, Stéphane; Léveillard, Thierry; Smirnov, Vasily; Vincent, Ajoy; Héon, Elise; Sahel, José-Alain; Kloeckener-Gruissem, Barbara; Sennlaub, Florian; Morgans, Catherine W.; Duvoisin, Robert M.; Tkatchenko, Andrei V.; Picaud, Serge
• Is Part Of: Progress in retinal and eye research. Volume 93(2023)
• Publication Date: 2023-03
• Subjects: Congenital stationary night blindness -- Myopia -- Retina -- Transcriptome sequencing -- meta-Analysis; Retina -- Periodicals; Retina -- Research -- Methodology -- Periodicals; Eye -- Diseases -- Periodicals; Eye -- Periodicals; Eye Diseases -- Periodicals; Retina -- Periodicals; Rétine -- Périodiques; Rétine -- Recherche -- Méthodologie -- Périodiques; 617.7005
• DOI: 10.1016/j.preteyeres.2022.101155
• Languages: English
• ISSNs: 1350-9462

Abstract

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. Highlights: Understanding the mechanisms of CSNB-related myopia. Implication of the ON-bipolar cell pathway in the development of myopia. RNA-Seq on cCSNB to identify candidates of retinal signaling and myopia. Meta-analysis comparing DEGs with transcriptomic, pathway and myopia databases. Half of the differentially expressed genes in cCSNB are known myopia-related genes.