Cases Olivier, Joseph Antoine, Obry Antoine, Santin Mathieu D, Ben-Yacoub Sirine, Pâques Michel, Amsellem-Levera Sabine, Bribian Ana, Simonutti Manuel, Augustin Sébastien, Debeir Thomas, Sahel José Alain, Christ Annabel, de Castro Fernando, Lehéricy Stéphane, Cosette Pascal, Kozyraki Renata
INSERM, U968, Paris, F-75012, France; UPMC Univ Paris 06, UMR_S968, Institut de la Vision, Paris, F-75012, France; CNRS, UMR_7210, Paris, F-75012, France.
CNRS, UMR_6270, PISSARO Proteomics Platform, Institute for Research and Innovation in Biomedicine, Rouen University Hospital, Rouen, F-76821, France; INSERM, U905, PISSARO Proteomics Platform, Institute for Research and Innovation in Biomedicine, Rouen University Hospital, Rouen, F-76821, France.
PLoS One. 2015 Jun 24;10(6):e0129518. doi: 10.1371/journal.pone.0129518. eCollection 2015.
Myopia is a common ocular disorder generally due to increased axial length of the eye-globe. Its extreme form high myopia (HM) is a multifactorial disease leading to retinal and scleral damage, visual impairment or loss and is an important health issue. Mutations in the endocytic receptor LRP2 gene result in Donnai-Barrow (DBS) and Stickler syndromes, both characterized by HM. To clearly establish the link between Lrp2 and congenital HM we inactivated Lrp2 in the mouse forebrain including the neural retina and the retinal and ciliary pigment epithelia. High resolution in vivo MRI imaging and ophthalmological analyses showed that the adult Lrp2-deficient eyes were 40% longer than the control ones mainly due to an excessive elongation of the vitreal chamber. They had an apparently normal intraocular pressure and developed chorioretinal atrophy and posterior scleral staphyloma features reminiscent of human myopic retinopathy. Immunomorphological and ultrastructural analyses showed that increased eye lengthening was first observed by post-natal day 5 (P5) and that it was accompanied by a rapid decrease of the bipolar, photoreceptor and retinal ganglion cells, and eventually the optic nerve axons. It was followed by scleral thinning and collagen fiber disorganization, essentially in the posterior pole. We conclude that the function of LRP2 in the ocular tissues is necessary for normal eye growth and that the Lrp2-deficient eyes provide a unique tool to further study human HM.
近视是一种常见的眼部疾病，通常是由于眼球轴长增加所致。其极端形式的高度近视（HM）是一种多因素疾病，可导致视网膜和巩膜损伤、视力损害或丧失，是一个重要的健康问题。内吞受体LRP2基因的突变会导致多纳伊 - 巴罗（DBS）综合征和斯迪克勒综合征，这两种综合征均以高度近视为特征。为了明确建立Lrp2与先天性高度近视之间的联系，我们在小鼠前脑（包括神经视网膜、视网膜色素上皮和睫状体色素上皮）中使Lrp2失活。高分辨率体内MRI成像和眼科分析表明，成年Lrp2缺陷小鼠的眼睛比对照小鼠长40%，主要是由于玻璃体腔过度伸长。它们的眼压明显正常，并出现脉络膜视网膜萎缩和后巩膜葡萄肿特征，类似于人类近视性视网膜病变。免疫形态学和超微结构分析表明，在出生后第5天（P5）首次观察到眼睛长度增加，同时伴有双极细胞、光感受器和视网膜神经节细胞数量迅速减少，最终视神经轴突也减少。随后出现巩膜变薄和胶原纤维紊乱，主要发生在眼球后极。我们得出结论，LRP2在眼组织中的功能对于正常的眼球生长是必要的，并且Lrp2缺陷小鼠的眼睛为进一步研究人类高度近视提供了一个独特的工具。
