LRP2 A Myopic Hotspot between Environment and Genetics

Abstract

Myopia is typically due to the excessive growth of the eye resulting in blurred vision of distant objects. High myopia (HM) and its associated pathologies, i.e glaucoma, retinal detachments or myopic retinopathy are important causes of vision loss especially in young adults and their incidence is constantly on the rise. The mechanisms that regulate myopic eye growth are poorly understood but inherited, environmental and behavioral factors may contribute to the development of HM. HM is a cardinal feature of the Donnai-Barrow syndrome (DBS), a rare autosomal recessive condition combining facial dysmorphology, sensorineural hearing loss and proteinuria. DBS is caused by mutations in LRP2 encoding the low density lipoprotein receptor-related protein 2 (LRP2), a large endocytic receptor strongly expressed in the ocular epithelia and involved in the handling of various molecules including retinal, transthyretin, leptin or vitamin D. The ocular manifestations of DBS patients or mice lacking LRP2 specifically in the eye include excessively enlarged globes, increased axial length, retinal degeneration and detachments and normal intraocular pressure. Impaired formation of the endocytic apparatus is a common feature in the renal epithelia of DBS patients and the retinal pigment epithelium of the LRP2-deficient eyes suggesting that impaired transport or clearance of LRP2 ligands in the ocular tissues may be involved in myopia induction and progression. In this review we summarize current knowledge on myopia development and propose that modulating endocytosis of LRP2 and its ligands in the ocular tissues may be considered to prevent or control HM and its associated complications.