LRP2 is a potential molecular target for nonsyndromic pathological myopia
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.
Authors
- Kimberley Delaunay (ORCID: https://orcid.org/0000-0003-2960-4345)
- Francine Béhar‐Cohen (ORCID: https://orcid.org/0000-0001-8571-9513)
- Vidjea Cannaya
- Lasse Jørgensen Cehofski (ORCID: https://orcid.org/0000-0002-2150-7754)
- Renata Kozyraki (ORCID: https://orcid.org/0000-0001-9779-5898)
- Jorge Ruiz‐Medrano (ORCID: https://orcid.org/0000-0002-1105-9265)
- Alicia Torriglia (ORCID: https://orcid.org/0000-0003-1181-6710)
- José M. Ruiz‐Moreno (ORCID: https://orcid.org/0000-0001-9636-0788)
- Laurent Jonet (ORCID: https://orcid.org/0000-0003-4485-2582)
- Olivier Cases (ORCID: https://orcid.org/0000-0002-5678-7362)
- Bent Honoré (ORCID: https://orcid.org/0000-0002-3459-7429)
- Henrik Vorum (ORCID: https://orcid.org/0000-0002-7600-0731)
- Kentaro Kojima (ORCID: https://orcid.org/0000-0003-2347-4789)
- Émilie Picard (ORCID: https://orcid.org/0000-0002-2689-0510)
- Patricia Lassiaz (ORCID: https://orcid.org/0000-0002-4417-6177)
- Eric Pussard (ORCID: https://orcid.org/0000-0003-4532-6488)
Institutions
- Inserm (FR)
- Aarhus University (DK)
- Université Paris Cité (FR)
- Aalborg University Hospital (DK)
- Sorbonne Université (FR)
- Kyoto Prefectural University of Medicine (JP)
- Centre de Recherche des Cordeliers (FR)
- Hôpital Cochin (FR)
- Hospital Universitario Puerta de Hierro Majadahonda (ES)
- Hôpital Foch (FR)
- Bicêtre Hospital (FR)
- Université de Rouen Normandie (FR)
- University of Castilla-La Mancha (ES)
Publication Details
- Journal
- JCI Insight
- Published
- 2025-06-24
- DOI
- https://doi.org/10.1172/jci.insight.192929
- Citations
- 2
- Primary Topic
- Ophthalmology and Visual Impairment Studies
- Type
- article
- Field-Weighted Citation Impact
- 2.71
Funders
- Fondation de France
- A.P. Møller og Hustru Chastine Mc-Kinney Møllers Fond til almene Formaal