Trabecular Meshwork Abnormalities in a Model of Congenital Glaucoma Due to LTBP2 Mutation.

IF 5 2区 医学 Q1 OPHTHALMOLOGY
Odalys Torné, Kazuya Oikawa, Leandro B C Teixeira, Julie A Kiland, Gillian J McLellan
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Abstract

Purpose: To characterize early trabecular meshwork (TM) morphologic abnormalities in a feline model of human primary congenital glaucoma (PCG) caused by mutation in LTBP2.

Methods: Eyes from 41 cats, including 19 normal and 22 homozygous for LTBP2 mutation, across various postnatal stages (birth, 2 weeks, 5 weeks, and 12 weeks) were paraformaldehyde fixed, anterior segments dissected, post-fixed in glutaraldehyde, osmicated, and processed and sectioned for transmission electron microscopy. Cell morphology, nuclear shape, and intertrabecular space (ITS) were quantitatively assessed, and the structure of the fibrillar extracellular matrix in the TM was systematically evaluated.

Results: The earliest differences in TM morphology between PCG and normal cats were identified at 2 weeks postnatally. Elastic fibers in the TM were discontinuous and disorganized (P = 0.0122), and by 5 weeks of age PCG cats presented significantly less ITS (P = 0.0076) and morphologically rounder TM cells than normal cats (P = 0.0293). By 12 weeks of age, the ITS was further collapsed (P < 0.0001), and the TM cells were morphologically elongated and attenuated in PCG compared to controls (P = 0.0028).

Conclusions: In this feline model of PCG due to LTBP2 mutation, development of ultrastructural TM extracellular matrix abnormalities are first observed by 2 weeks and cellular abnormalities by 5 weeks of age. By 12 weeks of age, when intraocular pressure becomes significantly elevated, the TM morphologic abnormalities are already well established. These findings suggest that the postnatal period between 0 and 5 weeks of age is critical for TM and PCG development and progression in cats.

LTBP2突变导致先天性青光眼模型中的小梁网状结构异常
目的:研究因LTBP2突变导致人类原发性先天性青光眼(PCG)的猫科模型中早期小梁网(TM)形态异常的特征:对41只猫的不同出生后阶段(出生、2周、5周和12周)的眼睛(包括19只正常猫和22只LTBP2基因突变的同源猫)进行多聚甲醛固定,解剖前节,在戊二醛中进行后固定,渗透,处理并切片用于透射电子显微镜观察。对细胞形态、核形状和小梁间隙(ITS)进行了定量评估,并系统评估了TM中纤维细胞外基质的结构:结果:PCG猫与正常猫的TM形态差异最早出现在出生后2周。TM 中的弹性纤维不连续且杂乱无章(P = 0.0122),到 5 周龄时,PCG 猫的 ITS 明显比正常猫少(P = 0.0076),TM 细胞的形态也更圆(P = 0.0293)。到 12 周龄时,与对照组相比,PCG 猫的 ITS 进一步缩小(P < 0.0001),TM 细胞的形态变长和变小(P = 0.0028):结论:在这一LTBP2突变导致的猫PCG模型中,2周龄时首先观察到TM细胞外基质超微结构异常,5周龄时观察到细胞异常。到 12 周龄时,当眼压显著升高时,TM 形态异常已经形成。这些研究结果表明,出生后 0 到 5 周龄是猫 TM 和 PCG 发育和发展的关键时期。
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来源期刊
CiteScore
6.90
自引率
4.50%
发文量
339
审稿时长
1 months
期刊介绍: Investigative Ophthalmology & Visual Science (IOVS), published as ready online, is a peer-reviewed academic journal of the Association for Research in Vision and Ophthalmology (ARVO). IOVS features original research, mostly pertaining to clinical and laboratory ophthalmology and vision research in general.
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