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Publications

Journal Article Epublish

PubMed: 40553567 DOI: 10.1172/jci.insight.192929

LRP2 is a potential molecular target for nonsyndromic pathological myopia.

JCI Insight 10(15)

Authors: Kimberley Delaunay, Emilie Picard, Patricia Lassiaz, Laurent Jonet, Vidjea Cannaya, José Maria Ruiz-Moreno, Kentaro Kojima, Henrik Vorum, Bent Honoré, Jorge Ruiz-Medrano, Lasse Jørgensen Cehofski, Eric Pussard, Renata Kozyraki, Alicia Torriglia, Olivier Cases, Francine Behar-Cohen

Affiliations

  • Centre de Recherche des Cordeliers, Sorbonne Université, INSERM, Université de Paris Cité, Paris F-75006, France.
  • Servicio de Oftalmologia, Hospital universitario Puerta de Hierro-Majahonda, Universidad Castilla La Mancha, Albacete, Spain.
  • Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • Department of Ophthalmology, and.
  • Department of Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark.
  • Department of Biomedicine, Aarhus University, Aarhus, Denmark.
  • Department of Genetic and Hormonology, Assistance Publique-Hôpitaux de Paris, Hôpital du Kremlin Bicêtre, Université de Paris-Saclay, Kremlin-Bicetre F-94270, France.
  • INSERM U1096, Faculty of Health, University of Rouen, Rouen F-76000, France.
  • Assistance Publique-Hôpitaux de Paris, Hôpital Cochin Ophtalmopole, Paris F-75014, France.
  • Hôpital Foch, Department of Ophthalmology, Suresnes, France.

Abstract

High myopia (HM) and posterior staphyloma (PS) are major causes of vision loss worldwide. Genetic and environmental factors, especially light exposure, influence myopia. This study shows that low-density lipoprotein-related receptor type 2 (LRP2) levels are decreased in the vitreous of patients with HM and PS, and that in human donor eyes affected by PS, LRP2 expression was reduced in the neural retina and retinal pigment epithelium (RPE), with morphologic changes similar to those observed in the Foxg1-Cre-Lrp2fl/fl mouse that also develops PS. In human induced pluripotent stem cell-derived RPE cells, LRP2 silencing regulated genes involved in eye and neuronal development, visual perception, tissue remodeling, hormone metabolism, and RPE structure. Its expression increased under light exposure, particularly red light, but was downregulated by cortisol. These findings establish a link between LRP2, myopization, and environmental factors, highlighting its crucial role in nonsyndromic HM and PS. LRP2 appears to be a promising therapeutic target for HM treatment.

MeSH

Eye, Cells, Retina, Biomedical Research, Therapeutics, Myopia, Myopia, Degenerative