EN / 中文
您的位置： 首页 > 2025年2月 第40卷 第2期 > 文字全文
2023年7月 第38卷 第7期11
目录

新生血管性年龄相关性黄斑变性的分子组学研究进展

Research progress in molecular omics of neovascular age-related macular degeneration

来源期刊： 眼科学报 | 2025年2月 第40卷 第2期： 215-222 发布时间：2025-2-28 收稿时间：2025/2/13 15:11:05 阅读量：338
作者：
庄雪楠,
桂弥,
文峰,
关键词：
年龄相关性黄斑变性新生血管性分子组学疾病机制生物标志物
age-related macular degeneration neovascular molecular omics review
DOI：
10.12419/24110302
收稿时间：
2024-11-05 
修订日期：
2024-11-28 
接收日期：
2024-12-25 
年龄相关性黄斑变性(age-related macular degeneration, AMD)是老年人视力丧失的主要原因之一，其中新生血管性AMD (neovascular AMD, nAMD)以其进展迅速、严重损伤视力的特点，成为全球眼科研究的焦点。随着人口老龄化加剧，nAMD的疾病负担日益沉重，对其发病机制的深入研究和有效治疗策略的探 索迫在眉睫。近年来，高通量组学技术的蓬勃发展为解析nAMD复杂的分子病理机制提供了前所未有的机遇。基因组学、转录组学、蛋白质组学、代谢组学以及多组学整合分析，不仅有助于深入挖掘疾病相关的关键分子、通路和网络，也为发现新的生物标志物和潜在治疗靶点提供了新的视角。文章系统综述了近年来分子组学技术在nAMD研究中的最新进展，重点关注不同组学方法在各类生物样本研究中 的发现，分析多组学整合在揭示疾病机制和筛选生物标志物方面的优势，以期为该领域的未来研究提供参考。

Age-related macular degeneration (AMD) is one of the leading causes of vision loss in elderly population. Among its subtypes, neovascular AMD (nAMD) has become a global focus in ophthalmological research due to its rapid progression and severe vision impairment. With the acceleration of population aging, the disease burden of nAMD is increasingly heavy, making it urgent to conduct in-depth research on its pathogenesis and explore effective therapeutic strategies. In recent years, the rapid development of high-throughput omics technologies has provided unprecedented opportunities to decipher the complex molecular pathological mechanisms of nAMD. Genomics, transcriptomics, proteomics, metabolomics, and multi-omics integration analyses have not only helped to deeply explore disease-related key molecules, pathways, and networks but also provided new perspectives for discovering novel biomarkers and potential therapeutic targets. This review systematically summarizes the recent advances in molecular omics technologies in nAMD research, focusing on findings from different omics approaches across various biological samples, and analyzes the advantages of multi-omics integration in revealing disease mechanisms and screening biomarkers, aiming to provide references for future research in this field.

文章亮点

1. 关键发现

•  本综述系统总结了新生血管性AMD (neovascular AMD, nAMD)分子组学研究进展，归纳了多组学技术在血液、房水、玻璃体等样本中发现的关键差异分子（包 括基因多态性、ncRNAs、蛋白质和代谢物等），为深入理解疾病机制提供新视角。

2. 已知与发现

•   梳理了从单一组学到多组学整合的研究演进过程，深入分析了基因、转录、蛋白和代谢等多层次分子网络的研究现状， 揭示了 nAMD 发病机制研究的新方向。

3. 意义与改变

•   通过系统总结多组学研究进展，为未来 nAMD 的精准医疗研究提供了理论依据，对生物标志物的筛选和个体化治疗方 案的制定具有重要的指导意义。

       年龄相关性黄斑变性(age-related macular degeneration, AMD)是全球范围内老年人视力丧失的主要原因之 一，其患病率随着人口老龄化而不断攀升，给社会带 来沉重的医疗负担。据统计，2020年全球AMD患者约1.96亿，预计到2040年将增至2.88亿[1]。在中国，AMD 的患病率也呈上升趋势，从2010年的5.16%上升至2015 年的5.24%，预计2050年将达到7.64%，患者人数将达到约5 519万人[2-3] 。AMD主要分为非新生血管性AMD 与新生血管性AMD(neovascular AMD, nAMD) ，nAMD 虽然仅占AMD总病例的15%～20%，但由于其进展迅速，可在短期内导致严重的视力损害，已成为眼科领域的重大挑战，并显著影响患者的日常生活能力和心 理健康，严重降低生活质量[4] 。nAMD的发生、发展是一个复杂的多因素过程，涉及视网膜色素上皮细胞(retinal pigment epithelium, RPE)和感光细胞代谢异常、 氧化应激反应、慢性炎症以及异常血管生成等多个 环节的相互作用[5-7]。在低氧微环境下，缺氧诱导因子1-α(hypoxia-inducible factor 1-α, HIF-1 α)上调血管内 皮生长因子(vascular endothelial growth factor, VEGF)的表达，激活下游信号通路，促进新生血管的形成[8]。同时，代谢产物的异常累积会导致活性氧(reactive oxygen species, ROS)的过度产生，引发炎症反应，并通过补体系统的激活形成恶性循环，进一步加剧疾病进展[9]。
       尽管既往研究已初步揭示nAMD的部分关键病理环节，但其复杂的分子网络和调控机制仍有待深入探索。近年来，以基因组学、转录组学、蛋白质组学和代谢组学为代表的组学技术蓬勃发展，为nAMD的研究提供了新的契机，极大地拓展了研究的深度和广度[10-13] 。这些组学技术的应用，特别是对遗传变异的分析(基因组学)，对非编码RNA表达谱的分析(转录组学)，对蛋白质表达、修饰和相互作用的分析(蛋白质组学)以及对生物化学反应产物的分析(代谢组学)， 不仅有助于发现新的生物标志物，也为探索潜在的治 疗靶点提供了新的思路[12, 14-15] 。而分子多组学整合分 析能够从系统生物学的角度，更全面地揭示疾病发生 发展的分子网络，为个体化精准治疗方案的制定提供科学依据。本文将系统综述近年来分子组学技术在 nAMD研究中的最新进展，重点关注不同组学方法在 不同生物样本中的研究结果，分析多组学整合在揭示疾病机制和寻找生物标志物方面的优势，以期为未来的研究方向提供参考。

1 基因组学研究进展

       基因组学研究在nAMD领域取得了显著进展，揭示了该病显著的遗传异质性，为风险评估和个体化医疗策略的发展奠定了重要基础。遗传因素在AMD的发生发展中贡献度高达46%～71%，其中包含复杂的基因-基因和基因-环境相互作用[16] 。目前已知的AMD相关基因包括补体因子H(complement factor H, CFH)、年龄相关性黄斑变性易感性2/丝氨酸蛋白酶A1(age-related maculopathy susceptibility 2/high-temperature requirement factor A1, ARMS2/HTRA1)、肝脂肪酶(hepatic lipase, LIPC)、胆固醇酯转运蛋白(cholesterylester transfer protein, CETP) 、ATP结合盒转运体A1(ATP-binding cassette transporter A1, ABCA1)、基质金属蛋白酶组织抑制剂 3(tissue inhibitor of metalloproteinases 3, TIMP3)、X型胶原蛋白α1链(collagen type X alpha 1 chain, COL10A1)、VIII型 胶原蛋白α1链(collagen type VIII alpha 1 chain, COL8A1)、 血管内皮生长因子A(vascular endothelial growth factor A, VEGFA)和转化生长因子β受体1(transforming growth factor beta receptor 1, TGFBR1)等，这些基因参与了补体 系统、脂质代谢、细胞外基质重塑和血管生成等多个关键生物学过程[17-25]。现有研究已鉴定出34个与AMD 相关的易感基因位点，共同构成了nAMD的遗传风险图谱。其中， CFH和ARMS2基因是nAMD遗传易感性 的两大“基石”，贡献率高达20%[16] 。CFH基因的变异，尤其是Y402H多态性，可导致补体系统过度激活，引发慢性炎症和RPE损伤。ARMS2基因的多态性则可能通过影响血管生成、细胞外基质矿化和TGF-β 信号通路等过程，增加nAMD的风险。除了常见变异外，罕见变异，例如CFH基因中的R1210C突变，也与 AMD的早期发病和疾病进展显著相关[26]。尽管罕见变 异频率较低，但其高外显子变异频率对疾病风险的影响不容忽视，未来研究中需要加强对其关注。Cascella 等[27] 的研究不仅发现了CFH 、ARMS2和IL-8等基因的 多态性与nAMD风险显著相关，还揭示了一些基因-基因和基因-表型之间的相互作用，例如VEGFA基因与1 型脉络膜新生血管(choroidal neovascularization,CNV)之间的关联，提示不同人群的遗传背景和环境因素可能存 在差异。罕见变异，例如CFH基因中的R1210C突变， 对AMD的早期发病和疾病进展具有重要影响，是未来 研究的重点方向[26]。这些基因组学研究结果与其他组学，例如蛋白组学和代谢组学的研究结果相互印证，共同揭示了nAMD复杂的病理机制。不同种族人群的遗传背景差异，可能导致nAMD的易感性和临床表型也存在差异，因此需要针对不同人群制定相应的预防和治疗策略[27]。

2 转录组学研究进展

       转录组学研究通过高通量测序技术揭示了nAMD 发病过程中复杂的基因表达调控网络。芬兰湿性AMD患者血清中发现多个与氧化应激和炎症相关的mRNA 显著上调，包括氧化低密度脂蛋白受体1 (oxidized low density lipoprotein receptor 1, OLR1)、盐诱导激酶 1(salt-inducible kinase 1, SIK1)和凝血因子III(coagulation factor III, F3)等[28] 。在对RPE/脉络膜复合体的深入研究中， COL10A1则被鉴定为另一个重要的CNV发展因子。该基因在CNV模型中显著上调，实验证实抑制COL10A1可有效降低内皮细胞的增殖和管形成能 力，并导致其下游基因Snail家族转录抑制因子1(Snail family transcriptional repressor 1, SNAIL1)和血管生成素 2(angiopoietin-2, ANGPT2)在缺氧条件下表达降低[29] 。 进一步研究发现，流星素(meteorin，MTRN)在CNV发展过程中也扮演关键角色，其通过调控血管生成、 氧化应激和神经保护相关的通路发挥作用[30]。另一项研究在nAMD患者视网膜脉络膜组织中发现，表皮 生长因子样原纤维蛋白样细胞外基质蛋白1(epidermal growth factor-containing fibrillin-like extracellular matrix protein 1, EFEMP1)表达水平升高，功能研究表明其可通过调 节VEGF的表达来促进血管内皮细胞的血管形成和增殖[31]。而单细胞转录组测序为我们提供了更高分辨率 的视角，揭示了CNV发生过程中的细胞异质性和复杂 的细胞间相互作用网络。研究显示内皮细胞、成纤 维细胞和巨噬细胞等多种细胞亚群共同参与CNV的形成[32]。其中， CD11c+ 巨噬细胞表现出显著的促血管 生成特征，可通过VEGF信号通路、内皮细胞出芽、 细胞因子信号和纤维化等多个途径推动CNV的发 展[33] 。而在炎症信号网络中，分泌磷蛋白1(secreted phosphoprotein 1, SPP1)通路的激活与巨噬细胞的促炎症表型和吞噬活性密切相关，这一通路在晚期干性 和湿性AMD患者的黄斑神经视网膜中呈现显著的高 表达[34]。
       非编码RNA研究则为nAMD的分子机制探索提供 了新的视角。研究发现多个微RNA(microRNA, miRNA) 在nAMD患者血液和眼部组织中存在差异表达，如 miR-199a-3p 、miR-195-5p和miR-185-5p在泪液中上调表达，而miR-200b-3p则下调表达。这些miRNA可能作为潜在的生物标志物用于nAMD的早期诊断和治疗反应监测[35] 。miR-126在nAMD患者外周血和血清中表达显著升高，可能通过调控VEGF信号通路中的Sprouty 相关含EVH1结构域蛋白1(sprouty related EVH1 domain containing 1, SPRED1)和磷脂酰肌醇3-激酶调节亚基 2(phosphoinositide-3-kinase regulatory subunit 2, PIK3R2)等负调节因子，促进血管生成[36-38] 。miR-146a可能通过干扰白细胞介素1受体相关激酶1(interleukin 1 receptor associated kinase 1, IRAK1)和肿瘤坏死因子受体相关因子 6(TNF receptor associated factor 6, TRAF-6)的表达，调节 炎症反应和补体系统的活化[39-41]。此外，转运RNA-谷 氨酸-CTC片段(transfer RNA fragment-glutamic acid-CTC, tRF-Glu-CTC)作为一种新型转移RNA衍生的小RNA分子，可通过抑制vasohibin 1 触发内皮细胞管形成、迁移和炎症因子分泌[42] 。长链非编码RNA方面，ZNF503-AS1和LINC00167可以抑制视网膜色素上皮细胞的应激去分化，而PWRN2的过表达则加重了氧化应激诱导的RPE细胞凋亡和线粒体功能障碍[43]。然而，由于ncRNA表达的组织特异性，以及不同研究间样本来源 和检测方法的差异，目前的研究结果仍存在一定的不一致性，未来需要更多高质量的研究来进一步验证和完善[44-46]。

3 蛋白质组学研究进展

       nAMD的蛋白质组学研究涵盖了血液、房水、玻璃体、泪液以及Bruch膜/脉络膜复合体等多种生物样本，为我们从不同角度理解疾病的分子机制提供了重要信息。尽管样本来源各异，但不同研究间的结果呈现出一定的交叉和联系，提示nAMD的病理过程不仅 局限于眼部局部，还涉及全身性的改变。例如，氧化应激和炎症反应这两个在nAMD发病机制中扮演关键 角色的生物学过程，在几乎所有样本类型的蛋白质组 学研究中都有所体现。血清和Bruch膜/脉络膜复合体中均发现了与氧化应激相关的蛋白质表达上调[47-48]； 炎症相关蛋白的上调则在房水、玻璃体和泪液中得到了证实[49-51]。这表明氧化应激和炎症反应贯穿于nAMD的始终，并在局部和全身水平发挥作用。这种系统性 的病理改变也体现在脂质代谢紊乱上。血清和房水蛋白质组学研究均发现了脂质代谢相关蛋白的表达异 常，提示脂质代谢紊乱可能是nAMD发生、发展的关键因素，并可能与氧化应激和炎症反应存在复杂的相互作用[47, 49]。此外，细胞转运异常在血清和泪液中也有 所发现，提示细胞功能障碍在nAMD的发生发展中也起着重要作用[47, 51]。
       当然，现有蛋白质组学研究结果之间也存在一些差异，如某些蛋白质在不同研究中的表达变化方向不一致，这可能是由于样本类型、疾病阶段、治疗情况以及研究方法等多种因素造成的。例如， Coronado 等[49]发现载脂蛋白A-I和A-IV在对抗VEGF治疗反应不 良的nAMD患者房水中表达上调，而Kim等[52]则发现载 脂蛋白A-Ⅳ在地理性萎缩(geographic atrophy, GA)患者血 浆中表达下调。这种差异可能反映了nAMD不同亚型 或疾病阶段之间存在不同的脂质代谢模式。对于这些差异，需要进行深入的分析和探讨，并结合临床表型和影像学特征，才能更全面地理解nAMD的复杂分子机制，而不能简单地将某个蛋白的表达变化与nAMD的发生、发展直接关联。更重要的是，我们需要关注不同蛋白质之间、不同通路之间的相互作用。蛋白质组学研究也为寻找nAMD的生物标志物和治疗靶点提 供了重要线索。一些在多项研究中均发现差异表达的蛋白质，例如凝聚素、视蛋白、 PEDF 、RBP4、醛缩酶C、组织蛋白酶D、细胞角蛋白8、α-防御素和半乳凝素-3等，有望成为nAMD的生物标志物，用于疾病的早期诊断、风险评估、疾病分型以及治疗反应监 测[47-48, 50, 53-55] 。一些参与关键生物学通路的蛋白质，例如Hsp90、膜联蛋白A1、α-烯醇化酶、炎症诱导因子 1(allograft inflammatory factor 1, AIF-1)和ATP结合盒转运体 B1(ATP-binding cassette subfamily B member 1, ABCB1)等， 则可能成为nAMD治疗的潜在靶点[51, 56]。当然，要将这些潜在的生物标志物和治疗靶点真正应用于临床，还需要进行更大规模、更严格设计的临床研究来验证其有效性和安全性。

4 代谢组学研究进展

       代谢组学通过对生物化学反应中间及终末产物的分析，为了解nAMD的代谢异常提供了直接的证据[57]。目前的研究主要集中在血浆、血清、房水和粪便样本，研究结果显示nAMD患者的代谢紊乱涉及脂质代谢、能量代谢、氨基酸代谢和嘌呤代谢等多个层面。其中，脂质代谢紊乱尤为突出。Zhao等[58]通过对 nAMD患者血浆样本的代谢组学分析，构建了nAMD的全局代谢网络，并强调了甘油磷脂和鞘脂代谢通路的关键作用。他们发现，磷脂酰胆碱(phosphatidylcholine, PC)、神经酰胺(ceramide, Cer)、鞘磷脂(sphingomyelin, SM)和甘油三酯(triglyceride, TG)等脂质在nAMD患者血浆中存在显著差异表达，并利用机器学习方法构建了一个包含16种代谢物和脂质的判别生物标志物组，其中排名前三位的生物标志物均为脂质，进一步凸显了 脂质代谢通路在nAMD诊断中的潜力[58] 。Wei等[59]则关注于房水代谢组学的变化，发现心磷脂(cardiolipin, CL)、甘油二酯(diacylglycerol, DG)和TG等脂质在湿性 AMD患者的房水中表达上调，而Cer、单半乳糖基甘油二酯(monogalactosyldiacylglycerol, MGDG)和鞘氨醇 (sphingosine, SPH)等则表达下调，提示房水代谢组学也蕴藏着丰富的nAMD生物标志物信息。这些研究结果与Coronado等[49]在房水蛋白质组学中的发现相互呼应，其研究也发现了与脂质代谢相关的蛋白表达异常，提示nAMD相关的脂质代谢紊乱可能不仅体现在 代谢物水平，也体现在蛋白质调控层面。Yuan等[60]对 粪便和血清样本的代谢组学分析则提供了另一个视角，发现nAMD患者粪便中神经保护性代谢物(如棕榈酰乙醇酰胺)水平降低，而血清中不饱和脂肪酸(如肾上腺酸)和嘌呤代谢产物水平升高，提示肠道菌群失调 介导的代谢紊乱可能参与了nAMD的发生、发展。这 种系统性的代谢改变也体现在能量代谢的紊乱上。多项研究发现了与糖酵解和三羧酸循环相关的代谢物水 平发生改变，提示nAMD患者的能量代谢可能存在异常[60]。此外，Shen等[61] 的研究关注了血清代谢组与抗VEGF治疗反应之间的关系，发现LPC 18 ∶ 0可能是预测康柏西普治疗效果的潜在生物标志物。这为基于代谢组学的个体化治疗提供了新的思路，也提示我们未来可以进一步探索其他抗VEGF药物与代谢组学之间的 关联。nAMD的代谢异常是一个涉及多通路、多器官的复杂过程，其中脂质代谢紊乱尤为突出，并可能与 氧化应激、炎症反应、细胞功能障碍以及肠道菌群失 调等多种因素存在复杂的相互作用。

5 多组学整合分析

       nAMD的分子机制复杂，单一组学技术难以完整 描绘其全貌。多组学整合分析，通过结合不同组学的数据，例如基因组学、转录组学、蛋白质组学和代谢组学等，能够更全面地解析nAMD的分子网络，并有望发现新的生物标志物和治疗靶点。我们一项近期开展的研究，尝试将纵向三维病灶分析、蛋白质组学和代谢组学相结合，研究抗VEGF治疗对nAMD的分子响应，并取得了一些初步的成果[62]。该研究鉴定了房水中受抗VEGF治疗影响的蛋白质和代谢物，并分析了这些分子变化与nAMD病灶改变之间的相关性。其中， 我们发现纤维蛋白原α链(fibrinogen alpha chain, FGA)、 转醛醇酶1(transaldolase 1, TALDO1)和天门冬氨酸β-羟化酶(aspartate beta-hydroxylase, ASPH)的减少与病灶消退相关，而YIPF3的减少却与病灶消退不良相关[62]。该研 究尝试从更全面的角度去理解nAMD抗VEGF治疗的分子机制，并为解释治疗反应的个体差异提供了一些新的线索[62]。因此，整合多组学数据，或结合临床影像 学数据，能够为我们提供更深入、更精细的nAMD病理生理学信息。

6 小结与展望

       随着组学技术的快速发展，nAMD的研究已经进入了一个新的时代。分子组学技术的应用，为我们深入理解nAMD的分子机制、寻找新的生物标志物和治疗靶点提供了强大的工具。多组学整合分析通过整合不同层面的生物学信息，能够更全面地解析nAMD的 分子网络，并有望揭示疾病发生、发展的关键节点。 展望未来，nAMD的研究将更加注重通过大规模的纵向队列研究，收集不同疾病阶段、不同治疗方案下患者的多组学数据，并结合临床表型和影像学特征进行深入分析，以揭示nAMD进展的动态分子机制；利用人工智能和机器学习等先进技术，分析海量的组学数据，构建更精准的疾病预测模型和个体化治疗方案； 基于多组学研究成果，鉴定新的治疗靶点，并开发更 有效、更安全的nAMD治疗药物；以及基于患者的基因型、分子表型和临床特征，制定个体化的精准医疗方案，以最大限度地提高治疗效果，并减少不良反应。总之，多组学整合分析，将有助于我们更深入地 理解nAMD的复杂病理过程，并最终为个体化治疗和 新药研发提供更坚实的科学依据。

利益冲突

所有作者均声明不存在利益冲突。

开放获取声明

本文适用于知识共享许可协议 ( Cre at ive Commons)，允许第三方用户按照署名(BY)-非商业性使用(NC)-禁止演绎(ND)(CC BY-NC-ND)的方式共 享，即允许第三方对本刊发表的文章进行复制、发 行、展览、表演、放映、广播或通过信息网络向公众传播，但在这些过程中必须保留作者署名、仅限 于非商业性目的、不得进行演绎创作。

1、 Kor va- Gurung I, Kubin AM, Ohtonen P, et al. Incidence and prevalence of neovascular age-related macular degeneration: 15-year epidemiological study in a population-based cohort in Finland[J]. Ann Med, 2023, 55(1): 2222545. DOI:10.1080/07853890.2023.2222545. Kor va- Gurung I, Kubin AM, Ohtonen P, et al. Incidence and prevalence of neovascular age-related macular degeneration: 15-year epidemiological study in a population-based cohort in Finland[J]. Ann Med, 2023, 55(1): 2222545. DOI:10.1080/07853890.2023.2222545.
2、Song P, Du Y, Chan KY, et al. The national and subnational prevalence and burden of age-related macular degeneration in China[J]. J Glob Health, 2017, 7(2): 020703. DOI:10.7189/jogh.07.020703.Song P, Du Y, Chan KY, et al. The national and subnational prevalence and burden of age-related macular degeneration in China[J]. J Glob Health, 2017, 7(2): 020703. DOI:10.7189/jogh.07.020703.
3、Zhang Y, Chen A, Zou M, et al. Disease burden of age-related macular degeneration in China from 1990 to 2019: findings from the global burden of disease study[J]. J Glob Health, 2021, 11: 08009. DOI:10.7189/jogh.11.08009.Zhang Y, Chen A, Zou M, et al. Disease burden of age-related macular degeneration in China from 1990 to 2019: findings from the global burden of disease study[J]. J Glob Health, 2021, 11: 08009. DOI:10.7189/jogh.11.08009.
4、Man REK, Gan ATL, Fenwick EK, et al. Impact of incident age- related macular degeneration and associated vision loss on vision-related quality of life[J]. Br J Ophthalmol, 2022, 106(8): 1063-1068. DOI:10.1136/bjophthalmol-2020-318269.Man REK, Gan ATL, Fenwick EK, et al. Impact of incident age- related macular degeneration and associated vision loss on vision-related quality of life[J]. Br J Ophthalmol, 2022, 106(8): 1063-1068. DOI:10.1136/bjophthalmol-2020-318269.
5、Ambati J, Atkinson JP, Gelfand BD. Immunology of age-related macular degeneration[J]. Nat Rev Immunol, 2013, 13(6): 438-451. DOI:10.1038/nri3459.Ambati J, Atkinson JP, Gelfand BD. Immunology of age-related macular degeneration[J]. Nat Rev Immunol, 2013, 13(6): 438-451. DOI:10.1038/nri3459.
6、Jorgenson E, Melles RB, Hoffmann TJ, et al. Common coding variants in the HLA-DQB1 region confer susceptibility to age-related macular degeneration[J]. Eur J Hum Genet, 2016, 24(7): 1049-1055. DOI:10.1038/ejhg.2015.247.Jorgenson E, Melles RB, Hoffmann TJ, et al. Common coding variants in the HLA-DQB1 region confer susceptibility to age-related macular degeneration[J]. Eur J Hum Genet, 2016, 24(7): 1049-1055. DOI:10.1038/ejhg.2015.247.
7、Fleckenstein M, Keenan TDL, Guymer RH, et al. Age-related macular degeneration[J]. Nat Rev Dis Primers, 2021, 7(1): 31. DOI:10.1038/ s41572-021-00265-2.Fleckenstein M, Keenan TDL, Guymer RH, et al. Age-related macular degeneration[J]. Nat Rev Dis Primers, 2021, 7(1): 31. DOI:10.1038/ s41572-021-00265-2.
8、Sharma D, Lau E, Qin Y, et al. VEGF inhibition increases expression of HIF-regulated angiogenic genes by the RPE limiting the response of wet AMD eyes to aflibercept[J]. Proc Natl Acad Sci USA, 2024, 121(46): e2322759121. DOI:10.1073/pnas.2322759121.Sharma D, Lau E, Qin Y, et al. VEGF inhibition increases expression of HIF-regulated angiogenic genes by the RPE limiting the response of wet AMD eyes to aflibercept[J]. Proc Natl Acad Sci USA, 2024, 121(46): e2322759121. DOI:10.1073/pnas.2322759121.
9、 Marie M, Bigot K, Angebault C, et al. Light action spectrum on oxidative stress and mitochondrial damage in A2E-loaded retinal pigment epithelium cells[J]. Cell Death Dis, 2018, 9(3): 287. DOI:10.1038/s41419-018-0331-5. Marie M, Bigot K, Angebault C, et al. Light action spectrum on oxidative stress and mitochondrial damage in A2E-loaded retinal pigment epithelium cells[J]. Cell Death Dis, 2018, 9(3): 287. DOI:10.1038/s41419-018-0331-5.
10、Chung RH, Kang CY. A multi-omics data simulator for complex disease studies and its application to evaluate multi-omics data analysis methods for disease classification[J]. Gigascience, 2019, 8(5): giz045. DOI:10.1093/gigascience/giz045.Chung RH, Kang CY. A multi-omics data simulator for complex disease studies and its application to evaluate multi-omics data analysis methods for disease classification[J]. Gigascience, 2019, 8(5): giz045. DOI:10.1093/gigascience/giz045.
11、Hasin Y, Seldin M, Lusis A. Multi-omics approaches to disease[J]. Genome Biol, 2017, 18(1): 83. DOI:10.1186/s13059-017-1215-1.Hasin Y, Seldin M, Lusis A. Multi-omics approaches to disease[J]. Genome Biol, 2017, 18(1): 83. DOI:10.1186/s13059-017-1215-1.
12、Brown CN, Green BD, Thompson RB, et al. Metabolomics and age-related macular degeneration[J]. Metabolites, 2018, 9(1): 4. DOI:10.3390/metabo9010004.Brown CN, Green BD, Thompson RB, et al. Metabolomics and age-related macular degeneration[J]. Metabolites, 2018, 9(1): 4. DOI:10.3390/metabo9010004.
13、Ka arniran ta K, Uusitalo H, Bl asiak J, et al. Mechanisms of mitochondrial dysfunction and their impact on age-related macular degeneration[J]. ProgRetin Eye Res, 2020, 79: 100858. DOI:10.1016/ j.preteyeres.2020.100858.Ka arniran ta K, Uusitalo H, Bl asiak J, et al. Mechanisms of mitochondrial dysfunction and their impact on age-related macular degeneration[J]. ProgRetin Eye Res, 2020, 79: 100858. DOI:10.1016/ j.preteyeres.2020.100858.
14、 Wang Z, Gerstein M, Snyder M. RNA-Seq: a revolutionary tool for transcriptomics[J]. Nat Rev Genet, 2009, 10(1): 57-63. DOI:10.1038/ nrg2484. Wang Z, Gerstein M, Snyder M. RNA-Seq: a revolutionary tool for transcriptomics[J]. Nat Rev Genet, 2009, 10(1): 57-63. DOI:10.1038/ nrg2484.
15、 Moaddel R, Ubaida-Mohien C, Tanaka T, et al. Proteomics in aging research: a roadmap to clinical, translational research[J]. Aging Cell, 2021, 20(4): e13325. DOI:10.1111/acel.13325. Moaddel R, Ubaida-Mohien C, Tanaka T, et al. Proteomics in aging research: a roadmap to clinical, translational research[J]. Aging Cell, 2021, 20(4): e13325. DOI:10.1111/acel.13325.
16、Sobrin L, Seddon JM. Nature and nurture- genes and environment- predict onset and progression of macular degeneration[J]. Prog Retin Eye Res, 2014, 40: 1-15. DOI:10.1016/j.preteyeres.2013.12.004.Sobrin L, Seddon JM. Nature and nurture- genes and environment- predict onset and progression of macular degeneration[J]. Prog Retin Eye Res, 2014, 40: 1-15. DOI:10.1016/j.preteyeres.2013.12.004.
17、Meyers SM, Greene T, Gutman FA. A twin study of age-related macular degeneration[J]. Am J Ophthalmol, 1995, 120(6): 757-766. DOI:10.1016/s0002-9394(14)72729-1. Meyers SM, Greene T, Gutman FA. A twin study of age-related macular degeneration[J]. Am J Ophthalmol, 1995, 120(6): 757-766. DOI:10.1016/s0002-9394(14)72729-1.
18、 Perlee LT, Bansal AT, Gehrs K, et al. Inclusion of genotype with fundus phenotype improves accuracy of predicting choroidal neovascularization and geographic atrophy[J]. Ophthalmology, 2013, 120(9): 1880-1892. DOI:10.1016/j.ophtha.2013.02.007. Perlee LT, Bansal AT, Gehrs K, et al. Inclusion of genotype with fundus phenotype improves accuracy of predicting choroidal neovascularization and geographic atrophy[J]. Ophthalmology, 2013, 120(9): 1880-1892. DOI:10.1016/j.ophtha.2013.02.007.
19、 Poulsen P, Esteller M, Vaag A, et al. The epigenetic basis of twin discordance in age-related diseases[J]. Pediatr Res, 2007, 61(5 Pt 2): 38R-42R. DOI:10.1203/pdr.0b013e31803c7b98. Poulsen P, Esteller M, Vaag A, et al. The epigenetic basis of twin discordance in age-related diseases[J]. Pediatr Res, 2007, 61(5 Pt 2): 38R-42R. DOI:10.1203/pdr.0b013e31803c7b98.
20、Querques G, Benlian P, Chanu B, et al. Nutritional AMD treatment phase I (NAT-1): feasibility of oral DHA supplementation in age- related macular degeneration[J]. Eur J Ophthalmol, 2009, 19(1): 100-106. DOI:10.1177/112067210901900115.Querques G, Benlian P, Chanu B, et al. Nutritional AMD treatment phase I (NAT-1): feasibility of oral DHA supplementation in age- related macular degeneration[J]. Eur J Ophthalmol, 2009, 19(1): 100-106. DOI:10.1177/112067210901900115.
21、Raychaudhuri S, Iartchouk O, Chin K, et al. A rare penetrant mutation in CFH confers high risk of age-related macular degeneration[J]. Nat Genet, 2011, 43(12): 1232-1236. DOI:10.1038/ng.976.Raychaudhuri S, Iartchouk O, Chin K, et al. A rare penetrant mutation in CFH confers high risk of age-related macular degeneration[J]. Nat Genet, 2011, 43(12): 1232-1236. DOI:10.1038/ng.976.
22、Reynolds R, Elizabeth Hartnett M, Atkinson JP, et al. Plasma complement components and activation fragments: associations with age-related macular degeneration genotypes and phenotypes[J]. Invest Ophthalmol Vis Sci, 2009, 50(12): 5818-5827. DOI:10.1167/iovs.09-3928. Reynolds R, Elizabeth Hartnett M, Atkinson JP, et al. Plasma complement components and activation fragments: associations with age-related macular degeneration genotypes and phenotypes[J]. Invest Ophthalmol Vis Sci, 2009, 50(12): 5818-5827. DOI:10.1167/iovs.09-3928.
23、Reynolds R, Rosner B, Seddon JM. Serum lipid biomarkers and hepatic lipase gene associations with age-related macular degeneration[J]. Ophthalmology, 20 10, 1 17 (1 0) : 1 98 9 - 19 95 . DOI: 10 . 1 0 16 / j.ophtha.2010.07.009.Reynolds R, Rosner B, Seddon JM. Serum lipid biomarkers and hepatic lipase gene associations with age-related macular degeneration[J]. Ophthalmology, 20 10, 1 17 (1 0) : 1 98 9 - 19 95 . DOI: 10 . 1 0 16 / j.ophtha.2010.07.009.
24、Reynolds R, Rosner B, Seddon JM. Dietary omega-3 fatty acids, other fat intake, genetic susceptibility, and progression to incident geographic atrophy[J]. Ophthalmology, 2013, 120(5): 1020-1028. DOI:10.1016/ j.ophtha.2012.10.020.Reynolds R, Rosner B, Seddon JM. Dietary omega-3 fatty acids, other fat intake, genetic susceptibility, and progression to incident geographic atrophy[J]. Ophthalmology, 2013, 120(5): 1020-1028. DOI:10.1016/ j.ophtha.2012.10.020.
25、Ridker PM, Rifai N, Stampfer MJ, et al. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men[J]. Circulation, 2000, 101(15): 1767-1772. DOI:10.1161/01.cir.101.15.1767.Ridker PM, Rifai N, Stampfer MJ, et al. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men[J]. Circulation, 2000, 101(15): 1767-1772. DOI:10.1161/01.cir.101.15.1767.
26、Francis PJ, George S, Schultz DW, et al. The LOC387715 gene, smoking, body mass index, environmental associations with advanced age-related macular degeneration[J]. Hum Hered, 2007, 63(3-4): 212- 218. DOI:10.1159/000100046. Francis PJ, George S, Schultz DW, et al. The LOC387715 gene, smoking, body mass index, environmental associations with advanced age-related macular degeneration[J]. Hum Hered, 2007, 63(3-4): 212- 218. DOI:10.1159/000100046.
27、Cascella R, Strafella C, Caputo V, et al. Towards the application of precision medicine in age-related macular degeneration[J]. Prog Retin Eye Res, 2018, 63: 132-146. DOI:10.1016/j.preteyeres.2017.11.004.Cascella R, Strafella C, Caputo V, et al. Towards the application of precision medicine in age-related macular degeneration[J]. Prog Retin Eye Res, 2018, 63: 132-146. DOI:10.1016/j.preteyeres.2017.11.004.
28、Liukkonen%20M%2C%20Heloter%C3%A4%20H%2C%20Siintamo%20L%2C%20et%20al.%20Oxidative%20stress%20and%20inflammation-related%20mRNAs%20are%20elevated%20in%20serum%20of%20a%20Finnish%20wet%20AMD%20cohort%5BJ%5D.%20Invest%20Ophthalmol%20Vis%20Sci%2C%202024%2C%2065(13)%3A%2030.%20DOI%3A10.1167%2Fiovs.65.13.30.Liukkonen%20M%2C%20Heloter%C3%A4%20H%2C%20Siintamo%20L%2C%20et%20al.%20Oxidative%20stress%20and%20inflammation-related%20mRNAs%20are%20elevated%20in%20serum%20of%20a%20Finnish%20wet%20AMD%20cohort%5BJ%5D.%20Invest%20Ophthalmol%20Vis%20Sci%2C%202024%2C%2065(13)%3A%2030.%20DOI%3A10.1167%2Fiovs.65.13.30.
29、Lv D, Chen D, Wang Z, et al. COL10A1 is a novel factor in the development of choroidal neovascularization[J]. Microvasc Res, 2022, 139: 104239. DOI:10.1016/j.mvr.2021.104239.Lv D, Chen D, Wang Z, et al. COL10A1 is a novel factor in the development of choroidal neovascularization[J]. Microvasc Res, 2022, 139: 104239. DOI:10.1016/j.mvr.2021.104239.
30、 Delaunay K, Sellam A, Dinet V, et al. Meteorin is a novel therapeutic target for wet age-related macular degeneration[J]. J Clin Med, 2021, 10(13): 2973. DOI:10.3390/jcm10132973. Delaunay K, Sellam A, Dinet V, et al. Meteorin is a novel therapeutic target for wet age-related macular degeneration[J]. J Clin Med, 2021, 10(13): 2973. DOI:10.3390/jcm10132973.
31、Cheng L, Chen C, Guo W, et al. EFEMP1 overexpression contributes to neovascularization in age-related macular degeneration[J]. Front Pharmacol, 2020, 11: 547436. DOI:10.3389/fphar.2020.547436.Cheng L, Chen C, Guo W, et al. EFEMP1 overexpression contributes to neovascularization in age-related macular degeneration[J]. Front Pharmacol, 2020, 11: 547436. DOI:10.3389/fphar.2020.547436.
32、Tong M, Bai Y, Han X, et al. Single-cell profiling transcriptomic reveals cellular heterogeneity and cellular crosstalk in choroidal neovascularization model[J]. Exp Eye Res, 2024, 242: 109877. DOI:10.1016/j.exer.2024.109877.Tong M, Bai Y, Han X, et al. Single-cell profiling transcriptomic reveals cellular heterogeneity and cellular crosstalk in choroidal neovascularization model[J]. Exp Eye Res, 2024, 242: 109877. DOI:10.1016/j.exer.2024.109877.
33、Droho S, Rajesh A, Cuda CM, et al. CD11c+ macrophages are proang iogenic and necessary for experimental choroidal neo vascular ization[ J ] . JC I Insight, 2023, 8(7): e168142 . DOI:10.1172/jci.insight.168142.Droho S, Rajesh A, Cuda CM, et al. CD11c+ macrophages are proang iogenic and necessary for experimental choroidal neo vascular ization[ J ] . JC I Insight, 2023, 8(7): e168142 . DOI:10.1172/jci.insight.168142.
34、Lei S, Hu M, Wei Z. Single-cell sequencing reveals an important role of SPP1 and microglial activation in age-related macular degeneration[J]. Front Cell Neurosci, 2023, 17: 1322451. DOI:10 . 3389/ fncel.2023.1322451. Lei S, Hu M, Wei Z. Single-cell sequencing reveals an important role of SPP1 and microglial activation in age-related macular degeneration[J]. Front Cell Neurosci, 2023, 17: 1322451. DOI:10 . 3389/ fncel.2023.1322451.
35、Yen CY, Chiu CM, Fang IM. microRNA expression profiling in tears and blood as predictive biomarkers for anti-VEGF treatment response in wet age-related macular degeneration[J]. Graefe’s Arch Clin Exp Ophthalmol, 2024, 262(9): 2875-2884. DOI:10.1007/s00417-024- 06478-x.Yen CY, Chiu CM, Fang IM. microRNA expression profiling in tears and blood as predictive biomarkers for anti-VEGF treatment response in wet age-related macular degeneration[J]. Graefe’s Arch Clin Exp Ophthalmol, 2024, 262(9): 2875-2884. DOI:10.1007/s00417-024- 06478-x.
36、Fish JE, Santoro MM, Morton SU, et al. miR-126 regulatesangiogenic signaling and vascular integrity[J]. Dev Cell, 2008, 15(2): 272-284. DOI:10.1016/j.devcel.2008.07.008.Fish JE, Santoro MM, Morton SU, et al. miR-126 regulatesangiogenic signaling and vascular integrity[J]. Dev Cell, 2008, 15(2): 272-284. DOI:10.1016/j.devcel.2008.07.008.
37、Guenther%20SPW%2C%20Schrepfer%20S.%20miR-126%3A%20a%20potential%20new%20key%20player%20in%20hypoxia%20and%20reperfusion%3F%5BJ%5D.%20Ann%20Transl%20Med%2C%202016%2C%204(19)%3A%20377.%20DOI%3A10.21037%2Fatm.2016.08.22.Guenther%20SPW%2C%20Schrepfer%20S.%20miR-126%3A%20a%20potential%20new%20key%20player%20in%20hypoxia%20and%20reperfusion%3F%5BJ%5D.%20Ann%20Transl%20Med%2C%202016%2C%204(19)%3A%20377.%20DOI%3A10.21037%2Fatm.2016.08.22.
38、Wang S, Olson EN. AngiomiRs: key regulators of angiogenesis[J]. Curr Opin Genet Dev, 2009, 19(3): 205-211. DOI:10.1016/ j.gde.2009.04.002.Wang S, Olson EN. AngiomiRs: key regulators of angiogenesis[J]. Curr Opin Genet Dev, 2009, 19(3): 205-211. DOI:10.1016/ j.gde.2009.04.002.
39、Taganov KD, Boldin MP, Chang KJ, et al. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses[J]. Proc Natl Acad Sci USA, 2006, 103(33): 12481-12486. DOI:10.1073/pnas.0605298103.Taganov KD, Boldin MP, Chang KJ, et al. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses[J]. Proc Natl Acad Sci USA, 2006, 103(33): 12481-12486. DOI:10.1073/pnas.0605298103.
40、 Iyer A, Zurolo E, Prabowo A, et al. microRNA-146a: a key regulator of astrocyte-mediated inflammatory response[J]. PLoS One, 2012, 7(9): e44789. DOI:10.1371/journal.pone.0044789. Iyer A, Zurolo E, Prabowo A, et al. microRNA-146a: a key regulator of astrocyte-mediated inflammatory response[J]. PLoS One, 2012, 7(9): e44789. DOI:10.1371/journal.pone.0044789.
41、Bhaumik D, Scott GK, Schokrpur S, et al. microRNAs miR-146a/b negatively modulate thesenescence-associated inflammatory mediators IL -6 and IL -8[J]. Aging, 2009, 1(4): 402-411. DOI:10.18632/ aging.100042.Bhaumik D, Scott GK, Schokrpur S, et al. microRNAs miR-146a/b negatively modulate thesenescence-associated inflammatory mediators IL -6 and IL -8[J]. Aging, 2009, 1(4): 402-411. DOI:10.18632/ aging.100042.
42、Liang Y, Kong L, Zhang Y, et al. Transfer RNA derived fragment, tRF- Glu-CTC, aggravates the development of neovascular age-related macular degeneration[J]. Theranostics, 2024, 14(4): 1500-1516. DOI:10.7150/thno.92943.Liang Y, Kong L, Zhang Y, et al. Transfer RNA derived fragment, tRF- Glu-CTC, aggravates the development of neovascular age-related macular degeneration[J]. Theranostics, 2024, 14(4): 1500-1516. DOI:10.7150/thno.92943.
43、BlasiakJ, Hyttinen JMT, SzczepanskaJ, et al. Potential of long non- coding RNAs in age-related macular degeneration[J]. Int J Mol Sci, 2021, 22(17): 9178. DOI:10.3390/ijms22179178.BlasiakJ, Hyttinen JMT, SzczepanskaJ, et al. Potential of long non- coding RNAs in age-related macular degeneration[J]. Int J Mol Sci, 2021, 22(17): 9178. DOI:10.3390/ijms22179178.
44、Handa JT, Bowes Rickman C, Dick AD, et al. A systems biology approach towards understanding and treating non-neovascular age- related macular degeneration[J]. Nat Commun, 2019, 10(1): 3347. DOI:10.1038/s41467-019-11262-1.Handa JT, Bowes Rickman C, Dick AD, et al. A systems biology approach towards understanding and treating non-neovascular age- related macular degeneration[J]. Nat Commun, 2019, 10(1): 3347. DOI:10.1038/s41467-019-11262-1.
45、Ransohoff JD, Wei Y, Khavari PA. The functions and unique features of long intergenic non-coding RNA[J]. Nat Rev Mol Cell Biol, 2018, 19(3): 143-157. DOI:10.1038/nrm.2017.104.Ransohoff JD, Wei Y, Khavari PA. The functions and unique features of long intergenic non-coding RNA[J]. Nat Rev Mol Cell Biol, 2018, 19(3): 143-157. DOI:10.1038/nrm.2017.104.
46、Correia de Sousa M, Gjorgjieva M, Dolicka D, et al. Deciphering miRNAs' action through miRNA editing[J]. Int J Mol Sci, 2019, 20(24): 6249. DOI:10.3390/ijms20246249.Correia de Sousa M, Gjorgjieva M, Dolicka D, et al. Deciphering miRNAs' action through miRNA editing[J]. Int J Mol Sci, 2019, 20(24): 6249. DOI:10.3390/ijms20246249.
47、Winiarczyk M, Thiede B, Utheim TP, et al. Oxidative stress, persistent inflammation and blood coagulation alterations in serum proteome of patients with neovascular age-related macular degeneration[J]. Life, 2024, 14(5): 624. DOI:10.3390/life14050624.Winiarczyk M, Thiede B, Utheim TP, et al. Oxidative stress, persistent inflammation and blood coagulation alterations in serum proteome of patients with neovascular age-related macular degeneration[J]. Life, 2024, 14(5): 624. DOI:10.3390/life14050624.
48、Yuan X, Gu X, CrabbJS, et al. Quantitative proteomics: comparison of the macular Bruch membrane/choroid complex from age-related macular degeneration and normal eyes[J]. Mol Cell Proteomics, 2010, 9(6): 1031-1046. DOI:10.1074/mcp.M900523-MCP200.Yuan X, Gu X, CrabbJS, et al. Quantitative proteomics: comparison of the macular Bruch membrane/choroid complex from age-related macular degeneration and normal eyes[J]. Mol Cell Proteomics, 2010, 9(6): 1031-1046. DOI:10.1074/mcp.M900523-MCP200.
49、Coronado BNL, da Cunha FBS, de Oliveira RM, et al. Novel possible protein targets in neovascular age-related macular degeneration: a pilot study experiment[J]. Front Med (Lausanne), 2021, 8: 692272. DOI:10.3389/fmed.2021.692272.Coronado BNL, da Cunha FBS, de Oliveira RM, et al. Novel possible protein targets in neovascular age-related macular degeneration: a pilot study experiment[J]. Front Med (Lausanne), 2021, 8: 692272. DOI:10.3389/fmed.2021.692272.
50、 Santos FM, Ciordia S, Mesquita J, et al. Proteomics profiling ofvitreous humor reveals complement and coagulation components, adhesion factors, and neurodegeneration markers as discriminatory biomarkers of vitreoretinal eye diseases[J]. Front Immunol, 2023, 14: 1107295. DOI:10.3389/fimmu.2023.1107295. Santos FM, Ciordia S, Mesquita J, et al. Proteomics profiling ofvitreous humor reveals complement and coagulation components, adhesion factors, and neurodegeneration markers as discriminatory biomarkers of vitreoretinal eye diseases[J]. Front Immunol, 2023, 14: 1107295. DOI:10.3389/fimmu.2023.1107295.
51、Winiarczyk M, Winiarczyk D, Michalak K, et al. Dysregulated tear film proteins in macularedema due to the neovascular age-related macular degeneration are involved in the regulation of protein clearance, inflammation, and neovascularization[J]. J Clin Med, 2021, 10(14): 3060. DOI:10.3390/jcm10143060. Winiarczyk M, Winiarczyk D, Michalak K, et al. Dysregulated tear film proteins in macularedema due to the neovascular age-related macular degeneration are involved in the regulation of protein clearance, inflammation, and neovascularization[J]. J Clin Med, 2021, 10(14): 3060. DOI:10.3390/jcm10143060.
52、Lynch AM, Wagner BD, Weiss SJ, et al. Proteomic profiles in advanced age-related macular degeneration using anaptamer-based proteomic technology[J]. Transl Vis Sci Technol, 2019, 8(1): 14. DOI:10.1167/ tvst.8.1.14.Lynch AM, Wagner BD, Weiss SJ, et al. Proteomic profiles in advanced age-related macular degeneration using anaptamer-based proteomic technology[J]. Transl Vis Sci Technol, 2019, 8(1): 14. DOI:10.1167/ tvst.8.1.14.
53、Nobl M, Reich M, Dacheva I, et al. Proteomics of vitreous in neovascular age-related macular degeneration[J]. Exp Eye Res, 2016, 146: 107-117. DOI:10.1016/j.exer.2016.01.001.Nobl M, Reich M, Dacheva I, et al. Proteomics of vitreous in neovascular age-related macular degeneration[J]. Exp Eye Res, 2016, 146: 107-117. DOI:10.1016/j.exer.2016.01.001.
54、Künzel SE, Flesch LTM, Frentzel DP, et al. Systemic blood proteome patterns reflect disease phenotypes in neovascular age-related macular degeneration[J]. IntJ Mol Sci, 2023, 24(12): 10327. DOI:10.3390/ ijms241210327.Künzel SE, Flesch LTM, Frentzel DP, et al. Systemic blood proteome patterns reflect disease phenotypes in neovascular age-related macular degeneration[J]. IntJ Mol Sci, 2023, 24(12): 10327. DOI:10.3390/ ijms241210327.
55、 Kang GY, Bang JY, Choi AJ, et al. Exosomal proteins in the aqueous humor as novel biomarkers in patients with neovascular age-related macular degeneration[J]. J Proteome Res, 2014, 13(2): 581-595. DOI:10.1021/pr400751k. Kang GY, Bang JY, Choi AJ, et al. Exosomal proteins in the aqueous humor as novel biomarkers in patients with neovascular age-related macular degeneration[J]. J Proteome Res, 2014, 13(2): 581-595. DOI:10.1021/pr400751k.
56、Winiarczyk M, Kaarniranta K, Winiarczyk S, et al. Tear film proteome in age-related macular degeneration[J]. Graefes Arch Clin Exp Ophthalmol, 2018, 256(6): 1127-1139. DOI:10.1007/s00417-018- 3984-y.Winiarczyk M, Kaarniranta K, Winiarczyk S, et al. Tear film proteome in age-related macular degeneration[J]. Graefes Arch Clin Exp Ophthalmol, 2018, 256(6): 1127-1139. DOI:10.1007/s00417-018- 3984-y.
57、Hou XW, Wang Y, Ke CF, et al. Metabolomics and biomarkers in retinal and choroidal vascular diseases[J]. Metabolites, 2022, 12(9): 814. DOI:10.3390/metabo12090814.Hou XW, Wang Y, Ke CF, et al. Metabolomics and biomarkers in retinal and choroidal vascular diseases[J]. Metabolites, 2022, 12(9): 814. DOI:10.3390/metabo12090814.
58、Zhao T, Li J, Wang Y, et al. Integrative metabolome and lipidome analyses of plasma in neovascular macular degeneration[J]. Heliyon, 2023, 9(10): e20329. DOI:10.1016/j.heliyon.2023.e20329.Zhao T, Li J, Wang Y, et al. Integrative metabolome and lipidome analyses of plasma in neovascular macular degeneration[J]. Heliyon, 2023, 9(10): e20329. DOI:10.1016/j.heliyon.2023.e20329.
59、Wei Q, Tu X, Qiu Q, et al. Untargeted metabolomic study of patients with wet age-related macular degeneration in aqueous humor[J]. Clin Interv Aging, 2024, 19: 1571-1580. DOI:10.2147/CIA.S475920.Wei Q, Tu X, Qiu Q, et al. Untargeted metabolomic study of patients with wet age-related macular degeneration in aqueous humor[J]. Clin Interv Aging, 2024, 19: 1571-1580. DOI:10.2147/CIA.S475920.
60、 Yuan Q, Zhu S, Yue S, et al. Alterations in faecal and serum metabolic profiles in patients with neovascular age-related macular degeneration[J]. Nutrients, 2023, 15(13): 2984. DOI:10.3390/ nu15132984. Yuan Q, Zhu S, Yue S, et al. Alterations in faecal and serum metabolic profiles in patients with neovascular age-related macular degeneration[J]. Nutrients, 2023, 15(13): 2984. DOI:10.3390/ nu15132984.
61、 Shen Y, Wang H, Xu X, et al. Metabolomics study of treatment response to conbercept of patients with neovascular age-related macular degeneration and polypoidal choroidalvasculopathy[J]. Front Pharmacol, 2022, 13: 991879. DOI:10.3389/fphar.2022.991879. Shen Y, Wang H, Xu X, et al. Metabolomics study of treatment response to conbercept of patients with neovascular age-related macular degeneration and polypoidal choroidalvasculopathy[J]. Front Pharmacol, 2022, 13: 991879. DOI:10.3389/fphar.2022.991879.
62、Zhuang X, Li M, Mi L, et al. Molecular responses of anti-VEGF therapy in neovascular age-related macular degeneration: integrative insights from multi-omics and clinical imaging[J]. Invest Ophthalmol Vis Sci, 2024, 65(10): 24. DOI:10.1167/iovs.65.10.24.Zhuang X, Li M, Mi L, et al. Molecular responses of anti-VEGF therapy in neovascular age-related macular degeneration: integrative insights from multi-omics and clinical imaging[J]. Invest Ophthalmol Vis Sci, 2024, 65(10): 24. DOI:10.1167/iovs.65.10.24.
上一篇
下一篇
作者登录
作者注册
审稿登录
编辑登录
其他期刊

  • 眼科学报

    主管：中华人民共和国教育部
    主办：中山大学
    承办：中山大学中山眼科中心
    主编：林浩添
    主管：中华人民共和国教育部
    主办：中山大学
    浏览

  • Eye Science

    主管：中华人民共和国教育部
    主办：中山大学
    承办：中山大学中山眼科中心
    主编：林浩添
    主管：中华人民共和国教育部
    主办：中山大学
    浏览
最新资讯

一亿年进化出的晶状体有多重要？

How important is the lens evolved in 100 million years?

发布于: 2022-12-01
推荐阅读
出版者信息

中山大学

中山大学中山眼科中心

眼科学术平台公众号
目录
中山大学医学期刊联盟
关注微信公众号
首页   | 关于我们  | 联系我们 粤ICP备11021180
关注微信公众号
粤ICP备11021180