June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Complete congenital stationary night blindness as a tool to study myopia
Author Affiliations & Notes
  • Wilmet Baptiste
    Genetics, Sorbonne Universite, Paris, Île-de-France, France
  • Jérome Roger
    Universite Paris-Saclay, Saclay, Île-de-France, France
  • Christelle Michiels
    Genetics, Sorbonne Universite, Paris, Île-de-France, France
  • Jacques Callebert
    Service of Biochemistry and Molecular Biology, Hopital Lariboisiere, Paris, Île-de-France, France
  • Robert Duvoisin
    Oregon Health & Science University, Portland, Oregon, United States
  • Juliette Varin
    Genetics, Sorbonne Universite, Paris, Île-de-France, France
  • Nuria Sánchez-Farías
    Genetics, Sorbonne Universite, Paris, Île-de-France, France
  • Frank Schaeffel
    Institute of Molecular and Clinical Ophthalmology Basel, Basel, Basel-Stadt, Switzerland
  • José-Alain Sahel
    Department of Ophtalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
    Sorbonne Universite, Paris, Île-de-France, France
  • Isabelle S Audo
    Genetics, Sorbonne Universite, Paris, Île-de-France, France
  • Christina Zeitz
    Genetics, Sorbonne Universite, Paris, Île-de-France, France
  • Footnotes
    Commercial Relationships   Wilmet Baptiste None; Jérome Roger None; Christelle Michiels None; Jacques Callebert None; Robert Duvoisin None; Juliette Varin None; Nuria Sánchez-Farías None; Frank Schaeffel None; José-Alain Sahel None; Isabelle Audo None; Christina Zeitz None
  • Footnotes
    Support  This work was supported by Agence Nationale de la Recherche (ANR-12-BSVS1–001201_GPR179 and ANR-22-CHIN-0006); Institut Clinique de la Souris-ICS, Illkirch, France; Retina France; Valentin Haüy and AFM; IRP-INSERM; Dalloz—Institut de France; Fondation Voir et Entendre; Fondation de l’œil—Fondation de France, Ville de Paris and Region Ile de France; Labex Lifesenses (reference ANR-10-LABX-65), supported by French state funds managed by the ANR within the Investissements d’Avenir programme (ANR-11-IDEX-0004-0); the Programme Investissements d’Avenir IHU FOReSIGHT (ANR-18-IAHU-01); NIH grant EY029985; Essilor, The Fondation pour la Recherche Medicale (FRM) in partnership with the Fondation Roland Bailly, Ile de Paris and Region Ile de France, UNADEV-Aviesan call 2015, SENSGENE and ERN-EYE.
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 5235. doi:
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      Wilmet Baptiste, Jérome Roger, Christelle Michiels, Jacques Callebert, Robert Duvoisin, Juliette Varin, Nuria Sánchez-Farías, Frank Schaeffel, José-Alain Sahel, Isabelle S Audo, Christina Zeitz; Complete congenital stationary night blindness as a tool to study myopia. Invest. Ophthalmol. Vis. Sci. 2023;64(8):5235.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : Myopia is a multifactorial eye disorder caused by genetic and environmental factors and inhibited by light exposure. Complete congenital stationary night blindness (cCSNB) is a retinal disorder associated with high myopia in patients and caused by a signal transmission defect between photoreceptors and ON-bipolar cells. Our project aims to shed light on mechanisms implicated in myopia using cCSNB mouse models. We hypothesized that the cCSNB-related disruption of retinal signaling has the same effect as the absence of light which may lead to altered expression of myopia-related genes.

Methods : To investigate the molecular basis of myopia in cCSNB and to identify novel proteins involved in the retinal signaling cascade, we performed whole transcriptome sequencing (RNA-Seq) in three different mouse models of cCSNB (Gpr179-/-, Lrit3-/- and Grm6-/-) and their wild-type littermates. To validate that cCSNB mouse models develop myopia, retinal levels of dopamine (DA) and its metabolite 3,4 dihydroxyphenylacetic acid (DOPAC) were measured using ultra performance liquid chromatography. The induction of myopia was performed using a lens-induced myopia (LIM) protocol and the myopic shift was measured using an infrared photorefractometer. Differentially expressed genes (DEGs) were investigated, according to their expression in specific retinal cell types, their association with the term “myopia” in public databases and validated on RNA and protein levels.

Results : RNA-Seq data obtained from cCSNB mouse models revealed DEGs expressed in different retinal cells and implicated in the mitogen-activated protein kinase, synaptic signaling, G protein-coupled receptor ligand binding pathways, and proteins implicated in tissue development (fold change ≥1.2, p-value ≤0.01). Half of the DEGs have been already associated with myopia. The retinal levels of both DA and DOPAC were drastically decreased in cCSNB mouse models, indicating a disruption of the dopaminergic pathway which can lead to myopia. After 3 weeks of LIM, Gpr179−/− mice were more myopic than Gpr179+/+ (p-value=0.0033). Preliminary data obtained in Lrit3-/- also showed a higher myopic shift compared to Lrit3+/+.

Conclusions : We show that cCSNB is a good model to study myopia. We identified cellular pathways involved in the onset of myopia occurring in cCSNB. This study provides the first steps to study myopia in cCSNB and for the guidance of pharmacological myopia therapies.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.


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