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城市颗粒物与眼表疾病及其潜在致病机制

Urban particulate matter related ocular surface diseases and their potential pathogenic mechanism

来源期刊： 眼科学报 | 2024年12月 第39卷 第12期： 648-656 发布时间：2024-12-28 收稿时间：2024/12/30 15:30:52 阅读量：2682
作者：
涂梦倩,
刘仁,
韩佳栩,
薛建文,
梁凌毅,
关键词：
城市颗粒物 空气污染眼表疾病
urban particulate matter air pollution ocular surface disease
DOI：
10.12419/24071501
收稿时间：
2024-08-08 
修订日期：
2024-08-30 
接收日期：
2024-09-30 
越来越多的证据表明，空气污染可严重损害人体健康，成为全球疾病负担的主要原因。并且污染空气中的主要成分空气颗粒物可渗透到肺部和心血管系统，引起缺血性心脏病、肺炎、慢性阻塞性肺疾病甚至肺癌，导致空气污染相关的发病率和死亡率升高。城市颗粒物作为城市居住人群面临的主要空气污染问题，被证实与多种炎症性眼表疾病密切相关，如过敏性结膜炎、角膜炎、干眼等。高浓度城市颗粒物暴露还会引起睑板腺病理性结构改变和功能异常，诱发炎性睑板腺功能障碍。文章综述了城市颗粒物相关的眼表疾病类型及其致病机制的最新研究，旨在阐明空气污染对于眼表组织的损害和相应的潜在治疗靶点，指导临床上环境相关眼病的诊断与治疗。
More and more evidence indicate that air pollution can seriously damage human health and become a major cause of the global disease burden. The main component of air pollution, particulate matter, can penetrate the lungs and cardiovascular system, causing ischemic heart disease, pneumonia, chronic obstructive pulmonary disease, and even lung cancer, leading to an increase in the incidence and mortality rates related to air pollution. Urban particulate matter, as the main air pollution problem faced by urban residents, has been shown to be closely related to various inflammatory eye diseases, such as allergic conjunctivitis, keratitis, and dry eye. Our research further confirms that exposure to high concentration of urban particulate matter can also cause pathological structural changes and functional abnormalities in the meibomian gland, leading to inflammatory meibomian gland dysfunction. This review comprehensively summarizes the latest research on the eye surface diseases related to urban particulate matter and their pathogenic mechanisms, aims to elucidate the damage of air pollution to eye surface tissues, identify potential therapeutic targets, and guide the diagnosis and treatment of environmentally related eye diseases in clinical practice.

文章亮点

1. 关键发现

通过汇总城市颗粒物与眼表疾病发生发展的相关性，归纳了城市颗粒物诱导眼表疾病的潜在致病机制。

2. 已知与发现

城市颗粒物污染作为城市居住人群面临的主要空气污染问题，被证实可通过激活免疫反应和氧化应激等多种病理信号，从而造成多种炎症性眼表疾病的发生。

3. 意义与改变

未来需关注空气污染严重城市人群的眼部健康，有必要通过筛查和保护措施来预防和治疗城市颗粒物污染诱导的眼表疾病。

       空气污染是一个全球性的公共卫生问题，可对人体健康构成重大威胁[1]。2015年的全球疾病负担、伤害和风险因素研究指出，空气污染是造成全球疾病负担的主要原因，尤其是在低收入和中等收入国家[2]。空气污染可影响人体几乎所有器官，提高多种疾病的发生率和死亡率，缩短预期寿命，因此被认为是迄今为止最重要的环境危险因素[3]。在众多空气污染物中，颗粒物是其重要的组成部分，并于2013年被世界卫生组织下属的国际癌症研究机构列为一类人类致癌物[4]。空气颗粒物主要来自人类的社会活动，例如工业排放、汽车尾气和建筑作业等。随着工业化和城市化进程的推进，城市内部的空气污染持续加重，鉴于城市人口密度较大，城市颗粒物（urban particulate matter, UPM）成为亟需探究和解决的主要问题[5]。
       UPM是一种复杂的混合物，由悬浮在空气中的固体和液体颗粒状物质组成，其粒径大小分布广泛，从纳米级到微米级不等，且粒径越小其穿透性越强[6]。UPM根据空气动力学直径大小和入肺能力，主要分为粗颗粒物（PM10）和细颗粒物（PM2.5）两类[7]。其中，PM10又称为可吸入颗粒物，其空气动力学直径不超过10 μm，可经由人体吸入并沉积于上呼吸道。PM2.5又称为入肺颗粒物，其直径不超过2.5 μm，能够随呼吸深入到细支气管，甚至到达肺泡[7]。因此，UPM与多种呼吸道疾病密切相关。此外，UPM的成分多样，携带多种毒性物质，包括金属、内毒素、氮氧化物和多环芳烃等[8]。研究者发现，UPM不仅具有促炎特性，还具有显著的遗传毒性和致癌性[9]。UPM入肺之后，可通过募集炎症细胞，释放促炎细胞因子和活性氧，引起呼吸道炎症和肺组织损伤[10-11]，从而导致哮喘[12]和慢性阻塞性肺疾病[13-14]进展，增加慢性阻塞性肺疾病的死亡率[15]。UPM还可通过DNA损伤、表观遗传调控等途径，促进肺癌的发生与发展[16]。除呼吸系统外，研究进一步表明，UPM中的细小成分或水溶性物质可穿透肺泡壁，进入血液循环[17]，影响血管张力，引起血压升高，增加心血管疾病的死亡风险[18]，甚至还可穿过血脑屏障，进入大脑，引起神经炎症和神经元突触改变，成为阿尔茨海默病等神经退行性疾病的重要致病因素[19]。由此可见，空气污染所导致的健康问题为社会带来了沉重的医疗负担和经济压力[20]。
       眼睛作为人体中少数直接暴露于外界环境的器官之一，其眼表微环境极易受到空气颗粒物的侵害[21]。流行病学研究表明，在空气污染严重的地区，居民经常出现眼痒、异物感、烧灼感和眼红等眼部不适症状[22-23]。眼科临床观察研究也进一步证实了UPM暴露与多种炎症性眼表疾病（包括过敏性结膜炎[24-25]、角膜炎[26]和干眼[27]等）高发病率之间的密切联系。此外，最近一项前瞻性多中心研究发现，UPM的暴露水平与睑脂的质量下降及睑板腺腺体缺失的发病率呈正相关，这提示UPM可能参与引起睑板腺功能障碍（meibomian gland dysfunction, MGD）相关的病理改变[28]。然而，对于UPM对睑板腺的潜在毒性损伤作用及其致病机制的认识目前仍然有限。需引起注意的是，UPM不仅可以损害眼表组织，还可对眼内组织造成不良危害。流行病学研究结果显示，UPM不仅与人群的高眼压，甚至于青光眼的发病有关[29]，还可引起白内障的发病率及手术事件增加[30]。此外，UPM还可通过破坏视网膜血管内皮细胞，穿透视网膜内屏障[31]，对视网膜微血管系统[32]，以及视网膜色素上皮[33]和神经[34]产生不利影响。
目前国内外对于UPM引起多组织器官损害的致病机制研究发现，UPM可通过激活一氧化氮合酶(nitric oxide synthase 2, NOS2)信号通路[35]、活性氧(reactive oxygen species, ROS)通路[36]、AMP激活蛋白激酶(AMP-activated protein kinase, AMPK)[37]和MyD88[38]介导的通路来诱导自噬的发生，其中多数信号通路与氧化应激和炎症相关。UPM诱导的细胞凋亡涉及人体的各个系统，可通过炎症相关信号通路来诱导，例如β2肾上腺素能受体/磷脂酰肌醇3激酶/蛋白激酶Bβ2AR/PI3K/Akt[39]、caspase3/c-Jun氨基末端激酶(c-Jun N-terminal kinase, JNK)/P53[40]、ROS-JNK/细胞外信号调节激酶(Extracellular signal-regulated kinase , ERK)[41]、丝裂原活化蛋白激酶(Mitogen-activated protein kinase, MAPK)/核因子-κB（nuclear factor kappa-B, NF-кB）/信号转导与转录激活因子1 (signal transducer and activator of transcription 1, STAT1)[42]等。除传统的细胞死亡形式外，UPM还可引发新型的调节性细胞死亡形式，例如细胞焦亡[43]。细胞焦亡又称细胞炎性坏死，是一种程序性细胞死亡，其特征是细胞不断扩增，直至细胞膜破裂，导致细胞内容物释放，从而引起大量炎症因子的流出，进而激活强烈的炎症级联反应[44]。UPM可通过焦亡诱导小鼠心脏结构改变和功能障碍[43]，影响血管形成[45]、神经递质的异常沉积[46]及神经元的损伤[47]，在循环系统、神经系统等多方面造成损害。
       鉴于空气污染物对于眼睛的不利影响，本综述将对有关UPM相关的眼表疾病及其致病机制的最新研究进行综合和总结，以帮助对眼部症状体征的理解和治疗方法的探究。

1 城市颗粒物相关结膜炎及其致病机制

       结膜是一层薄的半透明黏膜，由表面的上皮和其下的疏松结缔组织构成，覆盖在眼球前部，从角膜缘延伸至眼睑穹隆，然后向前至眼睑内侧[48]。结膜上皮由未角化、分层的鳞状上皮和分层柱状上皮以及散布的杯状细胞组成，其中杯状细胞分泌的黏蛋白构成了眼表泪膜的黏蛋白层，维持泪膜的稳态[49]。由于结膜血管化程度高，且经常暴露在外界环境中，容易受到病毒、细菌、过敏原、化学物质等各种有害因素的影响，从而导致结膜炎。结膜炎是由感染性和非感染性因素引起的炎症性疾病，可引起眼睛瘙痒、结膜肿胀、分泌物增多等[50]。严重的结膜炎甚至会使患者出现视力丧失或失明。结膜炎是急诊科最常见的眼病，对公共卫生和社会经济造成了沉重负担[51]。
       前期meta分析发现，空气污染是引发结膜炎的关键原因之一，其中空气中的二氧化氮(nitrogen dioxide, NO₂)、二氧化硫(sulfur dioxide，SO₂) 、臭氧 (ozone, O₃)和PM浓度的增加与非特异性结膜炎的门诊率升高密切相关[25]。结膜在受到空气中高浓度的UPM影响后，还可出现亚临床眼表改变，常表现为严重的眼部不适症状，严重影响人们的日常生活[52]。此外，长期暴露在空气污染中还会诱发细胞变化，例如结膜杯状细胞增生[53]，以及黏蛋白5AC基因表达量升高[54]。
       一项用UPM构建急性过敏性结膜炎小鼠模型的研究表明，在高浓度的UPM滴眼处理18 d后，小鼠出现睑结膜水肿、流泪和搔抓行为等与临床过敏性结膜炎患者相似的症状，提示UPM确实可诱导急性过敏性结膜炎的发生，并且上睑结膜的杯状细胞的密度增加，与既往临床研究一致，以及整个结膜出现了广泛的嗜酸性粒细胞浸润[55]。在另一项针对细颗粒物对小鼠眼表长期影响的体内外研究中，发现随着UPM水平的增加和处理时间的延长，结膜组织中的凋亡细胞随之增多，杯状细胞相应减少，IL-18、IL-22、IL-23 和单核细胞趋化蛋白-1 (monocyte chemotactic protein-1, MCP-1)在结膜组织中的表达量也明显升高[56]。近期一项基于小鼠模型探究UPM对眼表过敏性炎症的研究中，观察到UPM可通过增强淋巴结中T辅助2细胞(T helper 2 cell, Th2)免疫应答，促进树突状细胞的成熟、炎症细胞浸润和炎性因子IL-1β、IL-6、IL-17 和肿瘤坏死因子(tumor necrosis factor, TNF)的表达，以加重过敏性结膜炎[57]。 
       综上所述，UPM对结膜组织的损害主要通过炎症和免疫反应，细胞凋亡在其中也发挥了重要作用。对于既往研究中报道的UPM引起的结膜杯状细胞的改变的差异，可以理解为早期结膜在应对UPM刺激时，由于机体的代偿作用，而出现结膜杯状细胞增多，以维持眼表的稳态，当细胞凋亡到一定程度，使得细胞损害超过了机体的代偿能力，最终体现为杯状细胞的减少。

2 城市颗粒物相关角膜炎及其致病机制

       角膜位于眼球前部的中央，是高度透明的组织，其与乳白色巩膜共同构成了眼球壁的外层。角膜在裂隙灯显微镜下呈稍椭圆形，是屈光系统重要的构成部分。角膜的透明性和曲率可让光线正确聚焦于视网膜上，以产生最佳的视力。角膜的透明性取决于完整的角膜上皮细胞和泪膜、基质层胶原纤维束的规则排列，以及角膜无血管以及内皮细胞的功能[58]。然而，鉴于角膜位于眼表的浅层，其非常容易受到化学物质、空气中颗粒物和病原微生物等环境污染物的影响。当角膜受外界或内源性致病因素侵袭且诱发炎症时，可引起角膜浸润、溃疡，甚至穿孔，病变后期还可出现角膜瘢痕，基质层胶原纤维束排列紊乱，影响角膜的透明性，从而导致不同程度的视力下降，严重者可导致失明，影响患者的日常生活行动[59]。因此，保持角膜上皮的完整状态，对于其发挥屏障保护作用，保护眼内组织免受外界因素的影响，以及保持眼睛的功能和下层组织的完整性来说至关重要。
       根据流行病学研究结果，长时间的UPM暴露已被证实与角膜上皮损伤、破坏角膜上皮的屏障功能有关[60]。长期暴露于UPM的女性，也出现了浅表点状角膜炎和因角膜疾病引起的视力下降[61]。此外，实验室结果也进一步证明UPM不仅可以诱发干燥性角结膜炎，引起明显的角膜上皮损伤和形态不规则[62]，还可影响免疫功能，加速铜绿假单胞菌感染角膜的穿孔结局[63]。在小鼠模型中，也能观察到由于UPM的暴露导致角膜伤口愈合延迟[64]。
       近期一项基于单纯疱疹性角膜炎（herpes simplex keratitis, HSK）小鼠模型的空气污染暴露研究表明，暴露于UPM的HSK小鼠相较于对照组的HSK小鼠而言，拥有更大的病毒载量，并且发生了更严重的角膜混浊和新生血管的形成，促炎因子TNF-α、IL-1β、IFN-γ 的水平升高，趋化因子配体2 (chemokine (C-C motif) ligand 2, CCL2)合成增多，以及相应的角膜组织中CD4+和CD3+T细胞浸润增多，提示UPM的暴露可通过促进T细胞反应，来调节免疫功能，从而增加HSK易感性[26]。除上述的促炎因子外，NF-κB和IL-6也均可受UPM暴露的影响而升高，从而加剧炎症反应[65]。
       此外，角膜上皮细胞的体外实验研究同样为UPM相关角膜损伤的机制探索提供了重要帮助。根据最新发表的一项研究，人角膜上皮细胞在UPM处理后，出现了剂量和时间依赖性的细胞增殖抑制，以及与动物实验结果一致的ROS的生成。过量ROS在人角膜上皮细胞(human corneal epithelial cell, HCEC)中可引起线粒体ROS水平升高，从而导致线粒体膜电位降低，线粒体功能障碍，触发炎症级联反应。这一病理改变可通过Nrf2 过表达和 NF-κB P65 敲低来缓解，提示Nrf2表达抑制和 NF-κB P65 的过度激活在UPM诱导角膜损伤中的重要作用[66]。近年引起研究者关注的细胞焦亡，在UPM的角膜毒性作用中也被证实。在UPM处理过的HCEC中检测到了NLRP3炎症小体介导的焦亡轴相关蛋白NOD样受体热蛋白结构域相关蛋白3 (nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3, NLRP3)、凋亡相关斑点样蛋白(apoptosis-associated speck-like protein containing a caspase recruitment domain, ASC)、气孔蛋白D(gasdermin D, GSDMD)、caspase-1、IL-1β和IL-18表达上调，同时也伴有ROS的生成增多，为UPM诱导的角膜氧化应激损伤机制提供了新的方向[67]。UPM引起角膜上皮损伤的机制还涉及凋亡[56]、自噬[68]和坏死性凋亡[69]。角膜上皮的屏障功能主要依靠角膜上皮细胞间的紧密连接，而UPM的暴露可下调人角膜上皮细胞中的紧密连接和黏蛋白相关基因的表达，使细胞边界闭锁小带蛋白1(Zonula occludens protein 1, ZO-1)免疫反应性丧失，从而破坏角膜上皮的屏障功能[70]。
       如上所述，UPM通过调节细胞免疫功能，促进炎性因子表达，增加角膜炎的易感性，加重角膜炎的病理改变，导致角膜穿孔、混浊和新生血管形成，还可通过氧化应激降低细胞活力，诱导细胞凋亡、焦亡和自噬的发生，促进角膜上皮损伤。同时，也可以通过氧化还原失衡和炎症促进角膜上皮代偿性不规则增生，破坏细胞间的紧密连接，影响角膜的屏障功能。

3 城市颗粒物相关干眼及其致病机制

       干眼被定义为泪液和眼表的多因素疾病，导致不适、视力障碍和泪膜不稳定的症状，并可能对眼表造成损害，因其常伴有泪膜渗透压增加和眼表亚急性炎症[71]。眼表（角膜、结膜、副泪腺）、睑板腺（位于眼睑边缘的特定皮脂腺，产生泪膜的外脂质膜）、主要泪腺以及它们之间的神经支配形成一个功能单元。在干眼症中，这些结构都可能受到影响[72]。环境因素、感染、抗原、遗传因素等作用于眼表均可作为致病机制诱发干眼，与此同时，促炎细胞因子、趋化因子和基质金属蛋白酶会导致自身反应性Th细胞扩增，从而浸润眼表和泪腺组织，形成眼表损伤和炎症的恶性循环[72-73]。干眼可被分为泪液缺乏型干眼和蒸发过强型干眼[71]。最近的一项全球研究指出干眼的患病率约为11.59%，且患病率随年龄增长而显著增加，并且可损害功能性视力，尤其是在阅读、电脑或驾驶时，使得干眼患者的工作效率降低，生活质量下降[74]。干眼还被证实与焦虑症和抑郁症显著相关，因此，干眼所带来的卫生健康负担不容忽视[75-76]。
       在韩国进行的一项前瞻性观察性队列研究表明，较高浓度UPM的暴露与泪液分泌增加、泪膜破裂时间缩短、眼表疾病指数量表的评分升高密切相关，提示UPM的暴露导致了干眼患者的眼表不适症状加重以及泪膜稳定性下降[77]。同样，在我国杭州地区开展的一项时间分层的病例交叉设计研究报道了UPM与干眼患者的门诊就诊次数之间的显著关联，其中最易感的人群是21~40岁的人群（占研究患者总数的49.2%），此外，UPM与干眼门诊就诊次数之间的关联在寒冷季节比在温暖季节更强。研究者认为，UPM可能会通过改变角膜前泪膜结构，从而破坏其稳定性，导致眼部不适症状加重[27]。在我国开展的另一项横断面研究中，也报道了长期（≥143 d）的PM2.5暴露与干眼的诊断率呈正相关(OR = 2.01，95% CI为1.79~2.26)[78]。然而，在上述研究中发现PM10与干眼的诊断率和症状无关。
       对于UPM相关干眼的机制研究主要是通过滴眼方式来构建在体空气污染相关干眼动物模型，或者眼表上皮细胞的UPM处理体外实验。在通过将UPM悬液滴于小鼠眼表以构建的动物模型中观察到角膜出现了散在斑点状的缺损，以及与干眼患者表现一致的泪液分泌量的减少和泪膜破裂时间的缩短。通过对眼表组织进行形态学观察，发现小鼠角膜结膜的结构均发生了明显改变，同时，眼表组织也发生了炎症和氧化应激的激活[56]。在一项用PM2.5诱发小鼠干眼的研究中观察到了NF-κB通路的激活，并且其作为干眼的起始机制，驱动了角膜和泪腺组织的凋亡，眼表上皮细胞的增殖抑制，引起眼表组织发生强烈的炎症反应，从而导致干眼发生[79]。细胞凋亡参与了免疫细胞的发育、免疫调节、免疫作用等诸多生理和病理过程，在干眼这一免疫性疾病的发生、发展中起着重要作用[80]。
       由于使用局部滴眼方式探究UPM的暴露对眼表的影响仍存在局限性，未能反映大气环境中UPM的水平和作用模式，故而有学者设计了一种UPM气溶胶雾化系统，实验动物可以在其中长期生活，从而模拟UPM水平对真实环境中眼表和泪膜稳定性的影响。借助这一系统可建立合适的动物模型，使UPM暴露水平尽可能接近实际大气UPM，这对于研究UPM与人类疾病的关联以及相关的发病机制和临床治疗至关重要[81]。

4 城市颗粒物相关睑板腺功能障碍及其致病机制

       睑板腺是人体最大的皮脂腺，由导管和簇状的腺泡组成，其中央导管开口于睑缘，单个腺体于上下眼睑中平行排列，并垂直于睑缘[82]。睑板腺是一种全分泌型的产脂腺体，由三种上皮细胞组成，包括祖细胞、分化细胞（睑板腺细胞）和导管细胞[83]。成熟的睑板腺细胞的分化过程是细胞内部积累脂滴并细胞逐步解体的过程，最终将细胞内富含脂质的混合物（睑脂）释放于睑板腺中央导管中，进一步被运输到眼表，形成泪膜的脂质层[82]。任何引起睑板腺终末导管阻塞和（或）睑脂质或量变化的危险因素均将诱发MGD[84]。MGD是蒸发过强型干眼的主要原因，可能导致泪膜不稳定、泪液蒸发增加、泪液渗透压升高以及相关的眼部炎症[85]。MGD已成为一种非常普遍的疾病，在世界范围内的患病率约为35.8%。在某些国家，如中国、西班牙和日本，MGD的发病率超过50%[86]。MGD症状包括眼异物感、眼刺激、视觉障碍等，严重影响患者的日常生活和工作[87]。然而，MGD的确切发病机制尚不清楚，研究表明，炎症通过影响睑板腺的结构和功能，在MGD发生、发展中起着至关重要的作用[88]。
       目前关于UPM对睑板腺的毒性作用研究较少，但近期有一项关于长期和短期暴露于高水平UPM与MGD关系的前瞻性多中心研究表明，睑缘新生血管形成、睑脂分泌水平、睑脂质量和睑板腺腺体缺失与长期生活于高水平UPM环境呈中度相关。MGD的人群发病率和症状严重程度也均与UPM长期的暴露浓度呈正相关[28]。进一步的基础动物研究显示小鼠经UPM处理后，出现了明显的睑板腺开口堵塞、腺体缺失以及与既往研究相同的角膜上皮弥漫点状缺损表现。为阐明UPM相关的睑板腺腺体缺失，研究针对睑板腺的增殖潜能和细胞凋亡情况进行了检测，结果显示UPM组小鼠的睑板腺增殖和祖细胞标志物表达减少，凋亡细胞数量增多和细胞凋亡相关蛋白表达量明显上调，提示了UPM可通过抑制细胞增殖和促进细胞凋亡来导致睑板腺的腺体缺失。此外，睑板腺开口堵塞是MGD的另一重要的病理改变，其主要病因包括睑脂分泌量过多或成分异常导致其流动性下降，中央导管终末段过度角化，以及导管周边炎症细胞浸润。在UPM组小鼠中，均观察到了上述病理改变。研究结果还显示，细胞焦亡在UPM诱导MGD的病理过程中发挥重要作用，无论是腺泡细胞还是导管上皮，均发生了明显的焦亡，诱导了促炎细胞因子的大量释放，引起炎症级联反应，最终导致MGD，此外NF-κB和p38 MAPK的磷酸化水平明显上调。基于既往研究提出的NF-κB和p38 MAPK信号通路激活对于细胞焦亡诱导的重要作用，推测NF-κB和p38 MAPK信号通路在UPM诱导的MGD的发病过程中起着重要的驱动作用。

5 结论

        UPM与眼表疾病密切相关。长期暴露于高水平UPM会增加眼表疾病的发病率，随着暴露时间的延长和UPM水平的升高，眼表疾病的发生、发展会受到明显的影响，疾病的症状和严重程度也会加重，影响人群的生活质量。目前的研究表明，UPM可能是通过调节免疫反应、激活炎症、诱发氧化应激，同时促进细胞凋亡、细胞自噬、坏死性凋亡和焦亡，来诱导眼表损伤，最终导致结膜炎、角膜炎、干眼和MGD的发生和发展。当前，仍然需要通过细胞或动物模型的进一步实验研究以及临床研究，充分阐明UPM诱发眼表疾病的潜在机制，并指导环境相关眼病的治疗。同时，在空气污染严重的城市，尤其是UPM水平过高的地区，尤其要关注易感人群的眼表健康，通过筛查和保护措施来预防和治疗UPM诱导的眼表疾病。

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1、国家自然科学基金(82371021,82070922),广东省 自然科学基金(2023A1515012336)。
This work was supported by the National Natural Science Foundation of China (82371021, 82070922), the Science Foundation of Guangdong Province (2023A1515012336).This work was supported by the National Natural Science Foundation of China (82371021, 82070922), the Science Foundation of Guangdong Province (2023A1515012336). ( )
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