Delaunay Kimberley, Picard Emilie, Lassiaz Patricia, Jonet Laurent, Cannaya Vidjea, Ruiz-Moreno José Maria, Kojima Kentaro, Vorum Henrik, Honoré Bent, Medrano Jorge R, Cehofski Lasse Jørgensen, Pussard Eric, Kozyraki Renata, Torriglia Alicia, Cases Olivier, Behar-Cohen Francine
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.
JCI Insight. 2025 Jun 24;10(15). doi: 10.1172/jci.insight.192929. eCollection 2025 Aug 8.
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.
高度近视（HM）和后巩膜葡萄肿（PS）是全球视力丧失的主要原因。遗传和环境因素，尤其是光照，会影响近视。本研究表明，HM和PS患者玻璃体中低密度脂蛋白相关受体2（LRP2）水平降低，在受PS影响的人类供体眼中，神经视网膜和视网膜色素上皮（RPE）中的LRP2表达降低，其形态学变化与也发生PS的Foxg1-Cre-Lrp2fl/fl小鼠中观察到的变化相似。在人类诱导多能干细胞衍生的RPE细胞中，LRP2沉默调节参与眼睛和神经元发育、视觉感知、组织重塑、激素代谢和RPE结构的基因。其表达在光照下增加，尤其是红光，但被皮质醇下调。这些发现建立了LRP2、近视形成和环境因素之间的联系，突出了其在非综合征性HM和PS中的关键作用。LRP2似乎是HM治疗的一个有前景的治疗靶点。
