Maroteaux – Lamy syndrome (mucopolysaccharidosis type VI, MPS VI) is a lysosomal storage disease resulting from insufficient enzymatic activity for degradation of the specific glycosaminoglycans (GAG) chondroitin sulphate (CS) and dermatan sulphate (DS). Among the most pronounced MPS VI clinical manifestations caused by cellular accumulation of excess CS and DS are eye disorders, in particular those that affect the cornea. Ocular manifestations are not treated by the current standard of care, enzyme replacement therapy (ERT), leaving patients with a significant unmet need. Using in vitro and in vivo models, we previously demonstrated the potential of the β-D-xyloside, odiparcil, as an oral GAG clearance therapy for MPS VI. Here, we characterized the eye phenotypes in MPS VI arylsulfatase B deficient mice (Arsb⁻) and studied the effects of odiparcil treatment in early and established disease models. Severe levels of opacification and GAG accumulation were detected in the eyes of MPS VI Arsb⁻ mice. Histological examination of MPS VI Arsb⁻ eyes showed an aggregate of corneal phenotypes, including reduction in the corneal epithelium thickness and number of epithelial cell layers, and morphological malformations in the stroma. In addition, colloidal iron staining showed specifically GAG accumulation in the cornea. Orally administered odiparcil markedly reduced GAG accumulation in the eyes of MPS VI Arsb⁻ mice in both disease models and restored the corneal morphology (epithelial layers and stromal structure). In the early disease model of MPS VI, odiparcil partially reduced corneal opacity area, but did not affect opacity area in the established model. Analysis of GAG types accumulating in the MPS VI Arsb⁻ eyes demonstrated major contribution of DS and CS, with some increase in heparan sulphate (HS) as well and all were reduced with odiparcil treatment. Taken together, we further reveal the potential of odiparcil to be an effective therapy for eye phenotypes associated with MPS VI disease.

Maroteaux – Lamy 综合征（粘多糖贮积症 VI 型，MPS VI）是一种溶酶体贮积病，是由于对特定糖胺聚糖 (GAG) 硫酸软骨素 (CS) 和硫酸皮肤素 (DS) 的降解酶活性不足而导致的。由过量 CS 和 DS 的细胞积累引起的最明显的 MPS VI 临床表现是眼部疾病，特别是那些影响角膜的疾病。目前的护理标准酶替代疗法 (ERT) 无法治疗眼部症状，从而使患者的需求明显未得到满足。在体外和体内使用在模型中，我们之前证明了 β-D-木糖苷 odiparcil 作为 MPS VI 的口服 GAG 清除疗法的潜力。在这里，我们对 MPS VI 芳基硫酸酯酶 B 缺陷小鼠 ( Arsb ^- ) 的眼表型进行了表征，并研究了奥地帕西治疗在早期和已建立的疾病模型中的作用。在 MPS VI Arsb ^-小鼠的眼睛中检测到严重水平的混浊和 GAG 积累。MPS VI Arsb的组织学检查^-眼睛显示出多种角膜表型，包括角膜上皮厚度和上皮细胞层数的减少，以及基质中的形态畸形。此外，胶体铁染色显示角膜中特异性的GAG积累。在两种疾病模型中，口服奥地帕西显着减少了 MPS VI Arsb ^-小鼠眼中的 GAG 积累，并恢复了角膜形态（上皮层和基质结构）。在 MPS VI 的早期疾病模型中，odiparcil 部分减少了角膜混浊区域，但不影响已建立模型中的混浊区域。分析 MPS VI Arsb中累积的 GAG 类型^-眼睛表现出 DS 和 CS 的主要贡献，硫酸乙酰肝素 (HS) 也有所增加，并且所有这些都在 odiparcil 治疗后减少。总之，我们进一步揭示了 odiparcil 作为与 MPS VI 疾病相关的眼表型的有效疗法的潜力。