Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, United States; Vision Science and Investigative Ophthalmology Graduate Program, University of Miami, Miami, FL, United States; Miami Integrative Metabolomics Research Center, University of Miami, Miami, FL, United States.
Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, United States; Miami Integrative Metabolomics Research Center, University of Miami, Miami, FL, United States.
Adv Protein Chem Struct Biol. 2021;127:271-290. doi: 10.1016/bs.apcsb.2021.03.004. Epub 2021 Apr 26.
Pseudoexfoliation syndrome (PEX) is characterized by the production of white extracellular fluffy clumps of microfibrillar material that aggregates in various organs throughout the body but is known to cause disease in the eye. The accumulation of PEX material (PEXM) in the anterior segment ocular structures is believed to cause an increase in intraocular pressure (IOP) resulting in pseudoexfoliation glaucoma (PEXG). The onset of PEXG is often bilateral but asymmetric-one eye often presents with glaucoma prior to the other eye. Proteomics has been used to identify key proteins involved in PEXM formation with the end goal of developing effective treatments for PEX and PEXG which may act through inhibiting the formation of the PEX aggregates. To date, a variety of proteins with various molecular functions have been identified from extracted anterior segment structures and fluids, such as aqueous humor (AH) and blood serum of patients affected by PEX. From past studies, some proteins identified in AH, lens capsule epithelium, iris tissue, and blood serum samples include vitamin D binding protein (GC), apolipoprotein A4 (APOA4), lysyl oxidase like-1 (LOXL1), complement C3, beta-crystalline B1, and B2, and antithrombin-III (SERPINC1). Each of these proteins have been observed in eyes with PEX at varying levels within the different eye structures. In this review, we further examine the anterior segment ocular proteomics of PEXM from past studies to better understand the mechanism of PEX and PEXG development. Both genetic and environmental risk factors have been implicated to be involved in the development of PEX and PEXG. This field is at an early stage of investigation identifying how these factors modify proteins both at the expression and functional level to cause changes leading to the pathophysiology of PEX glaucoma.
假性剥脱综合征（PEX）的特征是产生白色细胞外蓬松状的微纤维物质簇，这些物质在全身各个器官中聚集，但已知会在眼部引起疾病。PEX 物质（PEXM）在前节眼部结构中的积聚被认为会导致眼内压（IOP）升高，从而导致假性剥脱性青光眼（PEXG）。PEXG 的发病通常是双侧的，但不对称——一只眼睛往往在另一只眼睛之前出现青光眼。蛋白质组学已被用于鉴定与 PEXM 形成相关的关键蛋白，最终目标是开发针对 PEX 和 PEXG 的有效治疗方法，这些方法可能通过抑制 PEX 聚集的形成来发挥作用。迄今为止，已经从提取的前节结构和液体（如房水（AH）和受 PEX 影响的患者血清）中鉴定出具有各种分子功能的各种蛋白质。过去的研究表明，在 AH、晶状体囊上皮、虹膜组织和血清样本中鉴定出的一些蛋白质包括维生素 D 结合蛋白（GC）、载脂蛋白 A4（APOA4）、赖氨酰氧化酶样-1（LOXL1）、补体 C3、β-晶体 B1 和 B2 以及抗凝血酶-III（SERPINC1）。在不同的眼部结构中，这些蛋白质在患有 PEX 的眼睛中以不同水平观察到。在这篇综述中，我们进一步检查了过去研究中 PEXM 的前节眼部蛋白质组学，以更好地了解 PEX 和 PEXG 发展的机制。遗传和环境风险因素都被认为与 PEX 和 PEXG 的发展有关。这一领域仍处于早期研究阶段，确定这些因素如何在表达和功能水平上修饰蛋白质，导致导致 PEX 青光眼病理生理学的变化。
