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Unravelling the molecular tapestry of pterygium: insights into genes for diagnostic and therapeutic innovations

Abstract

Pterygium, an ocular surface disorder, manifests as a wing-shaped extension from the corneoscleral limbus onto the cornea, impacting vision and causing inflammation. With a global prevalence of 12%, varying by region, the condition is linked to UV exposure, age, gender, and socioeconomic factors. This review focuses on key genes associated with pterygium, shedding light on potential therapeutic targets. Matrix metalloproteinases (MMPs), especially MMP2 and MMP9, contribute to ECM remodelling and angiogenesis in pterygium. Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis and is elevated in pterygium tissues. B-cell lymphoma-2, S100 proteins, DNA repair genes (hOGG1, XRCC1), CYP monooxygenases, p53, and p16 are implicated in pterygium development. A protein-protein interaction network analysis highlighted 28 edges between the aforementioned proteins, except for VEGF, indicating a high level of interaction. Gene ontology, microRNA and pathway analyses revealed the involvement of processes such as base excision repair, IL-17 and p53 signalling, ECM disassembly, oxidative stress, hypoxia, metallopeptidase activity and others that are essential for pterygium development. In addition, miR-29, miR-125, miR-126, miR-143, miR-200, miR-429, and miR-451a microRNAs were predicted, which were shown to have a role in pterygium development and disease severity. Identification of these molecular mechanisms provides insights for potential diagnostic and therapeutic strategies for pterygium.

摘要

翼状胬肉是一种眼表疾病, 表现为角膜巩膜缘向角膜延伸的翼状组织, 影响视力并产生炎症。该病的全球患病率为12%, 因地区而异, 与紫外线照射、年龄、性别和社会经济因素有关。本综述重点介绍与翼状胬肉相关的关键基因, 以揭示潜在的治疗靶点。基质金属蛋白酶 (MMPs), 尤其是 MMP2 和 MMP9, 有助于翼状胬肉中 ECM的重塑和血管生成。血管内皮生长因子 (VEGF) 在血管生成中发挥重要作用, 在翼状胬肉组织中含量升高。B 细胞淋巴瘤-2、S100 蛋白、DNA 修复基因 (hOGG1、XRCC1)、CYP 单加氧酶、p53 和 p16 与翼状胬肉的进展有关。蛋白质-蛋白质相互作用网络分析突出了上述蛋白质之间的 28 条边 (VEGF 除外),表明了高度的相互作用水平。基因本体论、microRNA 和通路分析揭示了诸如碱基切除修复、IL-17 和 p53 信号传导、ECM 分解、氧化应激、缺氧、金属肽酶活性等过程的参与, 这些过程对于翼状胬肉的进展至关重要。此外, 我们预测了 miR-29、miR-125、miR-126、miR-143、miR-200、miR-429 和 miR-451a microRNA, 这些 microRNA 被证实在翼状胬肉的进展和疾病严重程度中发挥作用。这些分子机制的识别为翼状胬肉的潜在诊断和治疗策略提供了见解。

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Fig. 1: Protein–protein interaction network.
Fig. 2: KEGG pathway and GO enrichment plots.
Fig. 3: microRNAs prediction analysis results are presented.

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RS, PA and HG conceived the idea. MG, SA, and RS collected the literature. MG performed the in silico analyses. MG, and RS generated the first draft of the manuscript. PA, and HG critically reviewed the manuscript. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Himanshu Gupta or Ruhi Sikka.

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Gupta, M., Arya, S., Agrawal, P. et al. Unravelling the molecular tapestry of pterygium: insights into genes for diagnostic and therapeutic innovations. Eye (2024). https://doi.org/10.1038/s41433-024-03186-y

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  • DOI: https://doi.org/10.1038/s41433-024-03186-y

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