Role of actin-binding proteins in cataract formation.

Christina Karakosta, Martina Samiotaki, George Panayotou, Dimitrios Papakonstantinou, Marilita M Moschos
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Abstract

Introduction: Actin has been implicated in lens opacification; however, the specific actin-related pathways involved in cataracts remain unelucidated. In this study, actin-related proteome changes and signaling pathways involved in the development of cataracts were evaluated.

Methods: The anterior capsule and phacoemulsification (phaco) cassette contents were collected during cataract surgery from 11 patients with diabetic cataract (DC), 12 patients with age-related cataract (ARC), and seven patients with post-vitrectomy cataract (PVC). Untargeted, global identification and quantification of proteins was performed through liquid chromatography-mass spectrometry with the data-independent acquisition (DIA).

Results: In phaco cassette samples, proteins with significantly lower expression in ARC than in DC and PVC were involved in various pathways, including actin binding, actin cytoskeleton reorganization, actin filament capping, cortical actin cytoskeleton organization, and small GTPase-mediated signal transduction pathways. In anterior capsules, proteins with significantly lower expression in ARC than in DC and PVC were involved in actin binding and actin cytoskeleton reorganization pathways.

Conclusion: Actin cytoskeleton and actin-binding proteins are involved in lens fiber elongation and differentiation. Rho GTPases contribute to actin cytoskeletal reorganization, and their inactivation is linked to abnormal lens fiber migration. These findings link actin binding to lens fiber integrity, lens opacification, and cataracts.

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肌动蛋白结合蛋白在白内障形成中的作用
导言:肌动蛋白被认为与晶状体不透明有关;然而,参与白内障的特定肌动蛋白相关通路仍未得到阐明。本研究评估了白内障发生过程中肌动蛋白相关蛋白质组的变化和信号通路:方法:在 11 名糖尿病白内障(DC)患者、12 名年龄相关性白内障(ARC)患者和 7 名玻璃体切除术后白内障(PVC)患者的白内障手术中收集了前囊和超声乳化(phaco)盒内容物。通过液相色谱-质谱联用技术(DIA)对蛋白质进行了非靶向、全面的鉴定和定量:在噬菌体盒样本中,ARC中的蛋白质表达量明显低于DC和PVC,这些蛋白质参与了各种途径,包括肌动蛋白结合、肌动蛋白细胞骨架重组、肌动蛋白丝封盖、皮质肌动蛋白细胞骨架组织和小GTP酶介导的信号转导途径。在前蒴果中,参与肌动蛋白结合和肌动蛋白细胞骨架重组途径的蛋白质在ARC中的表达量明显低于在DC和PVC中的表达量:结论:肌动蛋白细胞骨架和肌动蛋白结合蛋白参与了晶状体纤维的伸长和分化。结论:肌动蛋白细胞骨架和肌动蛋白结合蛋白参与了晶状体纤维的伸长和分化。Rho GTP酶有助于肌动蛋白细胞骨架重组,它们的失活与晶状体纤维的异常迁移有关。这些发现将肌动蛋白结合与晶状体纤维完整性、晶状体不透明和白内障联系起来。
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