Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States.
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States.
Invest Ophthalmol Vis Sci. 2024 Oct 1;65(12):28. doi: 10.1167/iovs.65.12.28.
To characterize early trabecular meshwork (TM) morphologic abnormalities in a feline model of human primary congenital glaucoma (PCG) caused by mutation in LTBP2.
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.
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).
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.
描述 LTBP2 突变所致人类原发性先天性青光眼（PCG）猫模型中早期小梁网（TM）形态异常的特征。
对 41 只猫的眼睛进行研究，包括 19 只正常猫和 22 只 LTBP2 突变纯合子猫，这些猫处于不同的出生后阶段（出生时、2 周、5 周和 12 周），用多聚甲醛固定，解剖前节，戊二醛后固定，锇酸固定，进行处理和切片，用于透射电镜检查。定量评估细胞形态、核形状和细胞间空间（ITS），并系统评估 TM 中纤维细胞外基质的结构。
在出生后 2 周时，PCG 猫和正常猫 TM 形态之间最早出现差异。TM 中的弹性纤维不连续且紊乱（P = 0.0122），到 5 周龄时，PCG 猫的 ITS 明显减少（P = 0.0076），TM 细胞形态也明显变圆（P = 0.0293）。到 12 周龄时，ITS 进一步塌陷（P < 0.0001），与对照组相比，PCG 猫的 TM 细胞形态拉长且变细（P = 0.0028）。
在 LTBP2 突变所致的这种猫原发性先天性青光眼模型中，最早在 2 周时观察到 TM 细胞外基质超微结构异常，最早在 5 周时观察到细胞异常。到 12 周龄时，眼内压显著升高，TM 形态异常已经确立。这些发现表明，猫的出生后 0 至 5 周龄之间对于 TM 和 PCG 的发育和进展至关重要。
