Madelyn E Erdman, Sanjay Ch, Amer Mohiuddin, Khalid Al-Kirwi, Molly R Rasper, Sibabalo Sokupa, Shermaine W Y Low, Christine M B Skumatz, Vinicius De Stefano, Iris S Kassem, Shyam S Chaurasia
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引用次数: 0
Abstract
Purpose: Fabry disease is an X-linked lysosomal storage disorder that results in multi-systemic renal, cardiovascular, and neuropathological damage, including in the eyes. We evaluated anterior segment ocular abnormalities based on age, sex (male and female), and genotype (wild-type, knockout [KO] male, heterozygous [HET] female, and KO female) in a rat model of Fabry disease.
Methods: The α-Gal A KO and WT rats were divided into young (6-24 weeks), adult (25-60 weeks), and aged (61+ weeks) groups. Intraocular pressure (IOP) was measured. Eyes were clinically scored for corneal and lens opacity as well as evaluated for corneal epithelial integrity and tear break-up time (TBUT). Anterior chamber depth (ACD) and central corneal thickness (CCT) using anterior segment-optical coherence tomography (AS-OCT).
Results: The Fabry rats showed an age-dependent increase in IOP, predominantly in the male genotype. TBUT was decreased in both male and female groups with aging. Epithelial integrity was defective in KO males and HET females with age. However, it was highly compromised in KO females irrespective of age. Corneal and lens opacities were severely affected irrespective of sex or genotype in the aging Fabry rats. AS-OCT quantification of CCT and ACD also demonstrated age-dependent increases but were more pronounced in Fabry versus WT genotypes.
Conclusions: Epithelial integrity, corneal, and lens opacities worsened in Fabry rats, whereas IOP and TBUT changes were age-dependent. Similarly, CCT and ACD were age-related but more pronounced in Fabry rats, providing newer insights into the anterior segment ocular abnormalities with age, sex, and genotype in a rat model of Fabry disease.
目的法布里病是一种 X 连锁溶酶体贮积症，会导致肾脏、心血管和神经等多系统病理损伤，包括眼部损伤。我们根据法布里病大鼠模型的年龄、性别（雄性和雌性）和基因型（野生型、基因敲除[KO]雄性、杂合子[HET]雌性和基因敲除[KO]雌性）对眼前节异常进行了评估：方法：将α-Gal A KO和WT大鼠分为幼年组（6-24周）、成年组（25-60周）和老年组（61周以上）。测量眼压（IOP）。对眼睛的角膜和晶状体混浊进行临床评分，并评估角膜上皮的完整性和泪液破裂时间（TBUT）。使用前段-光学相干断层扫描（AS-OCT）测量前房深度（ACD）和角膜中央厚度（CCT）：结果：法布里大鼠的眼压升高与年龄有关，主要发生在雄性基因型大鼠身上。随着年龄的增长，雄性和雌性组的 TBUT 均有所下降。随着年龄的增长，KO 雄性大鼠和 HET 雌性大鼠的上皮完整性出现缺陷。然而，KO 女性无论年龄大小，上皮完整性都会受到严重影响。无论性别或基因型如何，衰老法布里大鼠的角膜和晶状体不透明都受到严重影响。CCT和ACD的AS-OCT定量也显示出与年龄相关的增加，但在法布里基因型与WT基因型中更为明显：结论：法布里大鼠的上皮完整性、角膜和晶状体不透明恶化，而眼压和TBUT的变化与年龄有关。同样，CCT 和 ACD 也与年龄有关，但在法布里大鼠中更为明显，这为法布里病大鼠模型中眼前段异常与年龄、性别和基因型的关系提供了新的见解。
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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