PI3K/AKT信号通路在眼科疾病中的研究进展
Research Progress of the PI3K/AKT Signaling Pathway in Ophthalmic Diseases
DOI: 10.12677/jcpm.2025.42177, PDF,   
作者: 王佳乐：内蒙古医科大学内蒙古临床医学院，内蒙古 呼和浩特；格日勒图*：内蒙古自治区人民医院眼科，内蒙古 呼和浩特
关键词: PI3K/AKT信号通路；眼科疾病；调控作用；PI3K/AKT Signaling Pathway； Ophthalmic Diseases； Regulatory Role
摘要: 磷脂酰肌-3-激酶(PI3K)/丝氨酸–苏氨酸激酶(AKT)信号通路是细胞内重要的信号转导通路之一，PI3K/AKT通过影响下游的多种效应因子，形成不同的细胞通路从而参与细胞的各项调节，其在细胞增殖，迁移、分化和凋亡以及葡萄糖转运的过程中具有重要的作用，同时在眼科疾病的发生、发展过程起重要的调节作用。因此，通过对PI3K/Akt信号通路的研究有望寻求眼科疾病治疗的新靶点。本文将以PI3K/AKT信号通路的组成及其与眼科疾病的关系进行简要综述。
Abstract: Phosphatidylmuscle-3-kinase (PI3K)/serine-threonine kinase (AKT) signaling pathway is one of the important signal transduction pathways. PI3K/AKT forms different effectors of the downstream pathways to participate in the regulation of cell, including cell proliferation, migration, differentiation, apoptosis, and glucose transport, and in the occurrence and development of eye diseases. Therefore, research of the PI3K/Akt signaling pathway is expected to seek new targets for the treatment of ophthalmic diseases. A brief review will be conducted on the composition of the PI3K/AKT signaling pathway and its relationship to ophthalmic diseases.
文章引用：王佳乐, 格日勒图. PI3K/AKT信号通路在眼科疾病中的研究进展[J]. 临床个性化医学, 2025, 4(2): 294-302. https://doi.org/10.12677/jcpm.2025.42177

参考文献

[1] Yang, J., Nie, J., Ma, X., Wei, Y., Peng, Y. and Wei, X. (2019) Targeting PI3K in Cancer: Mechanisms and Advances in Clinical Trials. Molecular Cancer, 18, Article No. 26. [Google Scholar] [CrossRef] [PubMed]
[2] Engelman, J.A., Luo, J. and Cantley, L.C. (2006) The Evolution of Phosphatidylinositol 3-Kinases as Regulators of Growth and Metabolism. Nature Reviews Genetics, 7, 606-619. [Google Scholar] [CrossRef] [PubMed]
[3] Toren, P. and Zoubeidi, A. (2014) Targeting the PI3K/Akt Pathway in Prostate Cancer: Challenges and Opportunities (Review). International Journal of Oncology, 45, 1793-1801. [Google Scholar] [CrossRef] [PubMed]
[4] Bohdanowicz, M., Cosío, G., Backer, J.M. and Grinstein, S. (2010) Class I and Class III Phosphoinositide 3-Kinases Are Required for Actin Polymerization That Propels Phagosomes. Journal of Cell Biology, 191, 999-1012. [Google Scholar] [CrossRef] [PubMed]
[5] Xu, Z., Xia, Z., Wang, A., Wang, W., Liu, Z., Chen, L., et al. (2013) Activation of the PI3K/AKT/mTOR Pathway in Diffuse Large B Cell Lymphoma: Clinical Significance and Inhibitory Effect of Rituximab. Annals of Hematology, 92, 1351-1358. [Google Scholar] [CrossRef] [PubMed]
[6] Xu, F., Na, L., Li, Y. and Chen, L. (2021) Retraction Note To: Roles of the PI3K/AKT/mTOR Signalling Pathways in Neurodegenerative Diseases and Tumours. Cell & Bioscience, 11, Article No. 157. [Google Scholar] [CrossRef] [PubMed]
[7] Xie, Y., Shi, X., Sheng, K., Han, G., Li, W., Zhao, Q., et al. (2018) PI3K/AKT Signaling Transduction Pathway, Erythropoiesis and Glycolysis in Hypoxia (Review). Molecular Medicine Reports, 19, 783-791. Https://Doi.Org/10.3892/Mmr.2018.9713
[8] Hemmings, B.A. and Restuccia, D.F. (2015) The PI3K-PKB/Akt Pathway. Cold Spring Harbor Perspectives in Biology, 7, a026609. [Google Scholar] [CrossRef] [PubMed]
[9] Rajeeve, V., Pearce, W., Cascante, M., Vanhaesebroeck, B. and Cutillas, P.R. (2013) Polyamine Production Is Downstream and Upstream of Oncogenic PI3K Signalling and Contributes to Tumour Cell Growth. Biochemical Journal, 450, 619-628. [Google Scholar] [CrossRef] [PubMed]
[10] Cheng, H., Shcherba, M., Pendurti, G., Liang, Y., Piperdi, B. and Perez-Soler, R. (2014) Targeting the PI3K/AKT/mTOR Pathway: Potential for Lung Cancer Treatment. Lung Cancer Management, 3, 67-75. [Google Scholar] [CrossRef] [PubMed]
[11] Huang, W., Huang, G., Wang, D., Yin, Q., Foster, P.J. and He, M. (2011) Outcomes of Cataract Surgery in Urban Southern China: The Liwan Eye Study. Investigative Opthalmology & Visual Science, 52, 16-20. [Google Scholar] [CrossRef] [PubMed]
[12] Liegl, R., Wertheimer, C., Kernt, M., Docheva, D., Kampik, A. and Eibl-Lindner, K.H. (2013) Attenuation of Human Lens Epithelial Cell Spreading, Migration and Contraction via Downregulation of the PI3K/AKT Pathway. Graefe’s Archive for Clinical and Experimental Ophthalmology, 252, 285-292. [Google Scholar] [CrossRef] [PubMed]
[13] 蒲雅迪. miRNA-124通过PI3K/AKT/mTOR信号通路调控晶状体上皮细胞增殖、迁移及凋亡的机制研究[D]: [硕士学位论文]. 青岛: 青岛大学, 2021.
[14] Guo, R., Meng, Q., Guo, H., Xiao, L., Yang, X., Cui, Y., et al. (2015) TGF-β2 Induces Epithelial-Mesenchymal Transition in Cultured Human Lens Epithelial Cells through Activation of the PI3K/AKT/mTOR Signaling Pathway. Molecular Medicine Reports, 13, 1105-1110. [Google Scholar] [CrossRef] [PubMed]
[15] Xiong, W., Cheng, B., Jia, S. and Tang, L. (2010) Involvement of the PI3K/AKT Signaling Pathway in Platelet-Derived Growth Factor-Induced Migration of Human Lens Epithelial Cells. Current Eye Research, 35, 389-401. [Google Scholar] [CrossRef] [PubMed]
[16] 陶津华, 安小玲, 孔郡, 等. EGF体外对人晶状体上皮细胞迁移的影响[J]. 国际眼科杂志, 2006, 6(1): 68-71.
[17] Kayastha, F., Madhu, H., Vasavada, A. and Johar, K. (2014) Andrographolide Reduces Proliferation and Migration of Lens Epithelial Cells by Modulating PI3K/AKT Pathway. Experimental Eye Research, 128, 23-26. [Google Scholar] [CrossRef] [PubMed]
[18] Yao, L. and Yan, H. (2020) MiR-182 Inhibits Oxidative Stress and Epithelial Cell Apoptosis in Lens of Cataract Rats through PI3K/Akt Signaling Pathway. European Review for Medical and Pharmacological Sciences, 24, 12001-12008.
[19] 杨培增, 刘奕志. 眼科学[M]. 北京: 人民卫生出版社, 2017: 238-264.
[20] 王婧, 张楠, 余烁, 等. 内毒素耐受对内毒素诱导的葡萄膜炎炎症程度及虹膜睫状体中PI3K/AKT信号通路的影响[J]. 眼科, 2020, 29(1): 50-54.
[21] 张城. 鱼腥草水提取物治疗内毒素-诱导的葡萄膜炎(EIU)大鼠模型的疗效评价及其抗炎分子机制研究[D]: [硕士学位论文]. 杭州: 浙江中医药大学, 2023.
[22] Virgili, G., Gatta, G., Ciccolallo, L., Capocaccia, R., Biggeri, A., Crocetti, E., et al. (2007) Incidence of Uveal Melanoma in Europe. Ophthalmology, 114, 2309-2315.e2. [Google Scholar] [CrossRef] [PubMed]
[23] Grønborg, M., Kristiansen, T.Z., Iwahori, A., Chang, R., Reddy, R., Sato, N., et al. (2006) Biomarker Discovery from Pancreatic Cancer Secretome Using a Differential Proteomic Approach. Molecular & Cellular Proteomics, 5, 157-171. [Google Scholar] [CrossRef] [PubMed]
[24] 程英. MicroRNA-222介导PI3K/Akt/MMP-9信号通路参与调控HMGA1对葡萄膜黑色素瘤生物学功能的影响[D]: [博士学位论文]. 济南: 山东大学, 2020.
[25] 吴以加, 房燕, 沈菲洋, 等. FBXO38通过PI3K-Akt信号通路调控眼部黑色素瘤增殖[J]. 上海交通大学学报(医学版), 2023, 43(12): 1470-1479.
[26] 牟莹莹. Cx43、E-cadherin、PI3K及CTGF蛋白在脉络膜黑色素瘤中表达的研究[D]: [硕士学位论文]. 青岛: 青岛大学, 2011.
[27] 冯宇梁, 李杰, 刘巾男, 等. 视网膜脉络膜新生血管性疾病机制及治疗研究进展[J]. 西部医学, 2016, 28(9): 1328-1333.
[28] 艾明, 陈彬, 贺涛, 等. COX-2通过PI3K/Akt通路调节氧诱导视网膜病变模型中视网膜新生血管的形成[J]. 华中科技大学学报(医学版), 2009, 38(5): 655-659.
[29] 张月露. 网格蛋白4B对糖尿病视网膜病变新生血管的作用研究[D]: [博士学位论文]. 上海: 上海交通大学, 2018.
[30] 庄博, 张健, 孙铁权, 等. 阿柏西普减轻高糖诱导的视网膜色素上皮细胞损伤和PI3K/AKT信号通路活化[J]. 中国组织化学与细胞化学杂志, 2021, 30(3): 235-239.
[31] Stitt, A.W., Curtis, T.M., Chen, M., Medina, R.J., McKay, G.J., Jenkins, A., et al. (2016) The Progress in Understanding and Treatment of Diabetic Retinopathy. Progress in Retinal and Eye Research, 51, 156-186. [Google Scholar] [CrossRef] [PubMed]
[32] 陈飞. 硫化氢对高糖诱导的人视网膜色素上皮细胞氧化应激和炎症的影响[D]: [硕士学位论文]. 重庆: 重庆医科大学, 2018.
[33] 刘文强, 冯闯, 左中夫, 等. PI3K/Akt信号通路对高糖状态下视网膜Müller细胞的影响[J]. 眼科新进展, 2020, 40(11): 1024-1028.
[34] 唐德荣, 杨雨雯, 石蕊, 等. miR-26a-5p调控PTEN/PI3K/Akt信号通路对高糖诱导视网膜Müller细胞活化及凋亡的影响[J]. 西安交通大学学报(医学版), 2024, 45(5): 705-711.
[35] Li, J., Chen, K., Li, X., Zhang, X., Zhang, L., Yang, Q., et al. (2023) Mechanistic Insights into the Alterations and Regulation of the AKT Signaling Pathway in Diabetic Retinopathy. Cell Death Discovery, 9, Article No. 418. [Google Scholar] [CrossRef] [PubMed]
[36] 祝莹. BET抑制剂JQ1通过PI3K/AKT通路保护DR大鼠视网膜作用机制研究[D]: [博士学位论文]. 沈阳: 中国医科大学, 2021.
[37] 才娜. PI3K/AKT/mTOR信号通路抑制剂在视网膜色素上皮细胞增殖机制中的作用研究[D]: [博士学位论文]. 沈阳: 中国医科大学, 2018.
[38] Wang, P., Tian, X., Rong, J., Liu, D., Yi, G. and Tan, Q. (2011) Protein Kinase B (AKT) Promotes Pathological Angiogenesis in Murine Model of Oxygen-Induced Retinopathy. Acta Histochemica et Cytochemica, 44, 103-111. [Google Scholar] [CrossRef] [PubMed]
[39] Su, S., Zou, P., Yang, G., Wang, Y., Liu, L., Liu, Y., et al. (2022) Propranolol Ameliorates Retinopathy of Prematurity in Mice by Downregulating Hif-1α via the PI3K/AKT/ERK Pathway. Pediatric Research, 93, 1250-1257. [Google Scholar] [CrossRef] [PubMed]
[40] Hanus, J., Anderson, C. and Wang, S. (2015) RPE Necroptosis in Response to Oxidative Stress and in AMD. Ageing Research Reviews, 24, 286-298. [Google Scholar] [CrossRef] [PubMed]
[41] 张馨方, 盛迅伦. 视网膜色素变性的相关基因研究进展[J]. 国际眼科杂志, 2006, 6(3): 654-657.
[42] 杨梓超, 王育良, 左晶. 蒲黄提取物对糖尿病视网膜病变大鼠的保护作用[J]. 国际眼科杂志 2021, 21(3): 406-410.
[43] 傅文垚, 罗建平, 刘长虹. PI3K/AKT信号通路在常见神经退行性疾病中的机制研究进展[J]. 生物技术通讯, 2017, 28(6): 853-859.
[44] 王辉, 沈玲, 姬翔. DHA玻璃体注射对ARMD大鼠模型光感受器细胞凋亡和PI3K/Akt通路的影响[J]. 国际眼科杂志, 2019, 19(12): 2012-2016.
[45] 马明明. 间充质干细胞来源的外泌体对视网膜脱离的治疗作用[D]: [硕士学位论文]. 天津: 天津医科大学, 2019.
[46] 洪博, 崔蓓, 王凤翔, 等. 间充质干细胞来源外泌体对视网膜光感受器细胞PI3K/AKT通路及Ang-1蛋白水平作用的研究[J]. 转化医学杂志, 2022, 11(2): 70-75.
[47] 陆烨, 童剑萍. 视网膜母细胞瘤的发生机制及诊断和治疗进展[J]. 现代肿瘤医学, 2016, 24(6): 1007-1014.
[48] 杨夏, 吴涛. miR-130b在人视网膜母细胞瘤中的表达及促癌机制研究[J]. 国际眼科杂志, 2019, 19(2): 214-220.
[49] 安美霞, 张效房, 张金嵩. 挫伤性视网膜病变中光感受器细胞凋亡与氧化损伤的实验研究[J]. 中华眼科杂志, 2004, 40(2): 49-52.
[50] 王博. 颅脑爆震冲击波对视网膜损伤和PI3K/Akt通路及相关凋亡蛋白表达情况的研究[D]: [硕士学位论文]. 大连: 大连医科大学, 2021.
[51] 曹雪霞. 罂粟碱对SD大鼠原代视网膜神经节细胞轴突再生的影响及其作用机制的研究[D]: [硕士学位论文]. 郑州: 郑州大学, 2021.
[52] Williams, P.A., Marsh-Armstrong, N., Howell, G.R., Bosco, A., Danias, J., Simon, J., et al. (2017) Neuroinflammation in Glaucoma: A New Opportunity. Experimental Eye Research, 157, 20-27. [Google Scholar] [CrossRef] [PubMed]
[53] Weinreb, R.N., Aung, T. and Medeiros, F.A. (2014) The Pathophysiology and Treatment of Glaucoma. JAMA, 311, 1901-1911. [Google Scholar] [CrossRef] [PubMed]
[54] Jayaram, H., Kolko, M., Friedman, D.S. and Gazzard, G. (2023) Glaucoma: Now and Beyond. The Lancet, 402, 1788-1801. [Google Scholar] [CrossRef] [PubMed]
[55] 李雪如. S58通过激活PI3k/Akt/Nrf2信号通路抑制兔青光眼滤过性手术术后纤维化[D]: [硕士学位论文]. 重庆: 重庆医科大学, 2020.
[56] Zhao, N., Shi, J., Xu, H., Luo, Q., Li, Q. and Liu, M. (2021) Baicalin Suppresses Glaucoma Pathogenesis by Regulating the PI3K/AKT Signaling in Vitro and in Vivo. Bioengineered, 12, 10187-10198. [Google Scholar] [CrossRef] [PubMed]
[57] Craig, J.P., Nichols, K.K., Akpek, E.K., Caffery, B., Dua, H.S., Joo, C., et al. (2017) TFOS DEWS II Definition and Classification Report. The Ocular Surface, 15, 276-283. [Google Scholar] [CrossRef] [PubMed]
[58] Wu, C., Mao, J., Zhu, J., Xie, C., Yao, J., Yang, X., et al. (2023) DZ2002 Alleviates Corneal Angiogenesis and Inflammation in Rodent Models of Dry Eye Disease via Regulating STAT3-PI3K-AKT-NF-κB Pathway. Acta Pharmacologica Sinica, 45, 166-179. [Google Scholar] [CrossRef] [PubMed]
[59] Han, Y., Guo, S., Li, Y., Li, J., Zhu, L., Liu, Y., et al. (2023) Berberine Ameliorate Inflammation and Apoptosis via Modulating PI3K/AKT/NFκB and MAPK Pathway on Dry Eye. Phytomedicine, 121, Article ID: 155081. [Google Scholar] [CrossRef] [PubMed]
[60] 朱婷婷, 孙松. 翼状胬肉手术治疗方法研究进展[J]. 眼科新进展, 2011, 31(3): 293-296.
[61] 姚亮, 柏凌, 何娜, 等. PI3K/Akt/Bcl-2信号通路在原发性翼状胬肉中的机制研究[J]. 山西医科大学学报, 2017, 48(5): 441-444.
[62] Verma, S., Singh, A., Varshney, A., Chandru, R.A., Acharya, M., Rajput, J., et al. (2021) Infectious Keratitis: An Update on Role of Epigenetics. Frontiers in Immunology, 12, Article 765890. [Google Scholar] [CrossRef] [PubMed]
[63] 周洪伟. P物质在小鼠单纯疱疹病毒性角膜炎复发中的作用研究[D]: [博士学位论文]. 武汉: 武汉大学, 2016.
[64] 蒋浩. FGF5通过PI3K-AKT信号通路促进角膜上皮损伤修复机制研究[D]: [博士学位论文]. 贵州: 贵州医科大学, 2023.
[65] 丁辉, 胡施思, 杨镇朵, 等. 丁香酚通过PI3K/AKT信号通路减轻镰刀菌诱导的角膜炎症[J]. 国际眼科杂志, 2024, 24(8): 1194-1199.
[66] Chen, K., Li, Y., Zhang, X., Ullah, R., Tong, J. and Shen, Y. (2022) The Role of the PI3K/AKT Signalling Pathway in the Corneal Epithelium: Recent Updates. Cell Death & Disease, 13, Article No. 513. [Google Scholar] [CrossRef] [PubMed]
[67] Garrity, J.A. and Bahn, R.S. (2006) Pathogenesis of Graves Ophthalmopathy: Implications for Prediction, Prevention, and Treatment. American Journal of Ophthalmology, 142, 147-153.e2. [Google Scholar] [CrossRef] [PubMed]
[68] Zhang, Y., Li, X., Guo, C., Dong, J. and Liao, L. (2020) Mechanisms of Spica Prunellae against Thyroid-Associated Ophthalmopathy Based on Network Pharmacology and Molecular Docking. BMC Complementary Medicine and Therapies, 20, Article No. 229. [Google Scholar] [CrossRef] [PubMed]
[69] Woeller, C.F., Roztocil, E., Hammond, C. and Feldon, S.E. (2019) TSHR Signaling Stimulates Proliferation through PI3K/Akt and Induction of Mir-146a and Mir-155 in Thyroid Eye Disease Orbital Fibroblasts. Investigative Opthalmology & Visual Science, 60, 4336-4345. [Google Scholar] [CrossRef] [PubMed]
[70] 马飞. 视网膜Sonic hedgehog信号介导PI3K/AKT通路在豚鼠形觉剥夺性近视模型中的作用及机制研究[D]: [博士学位论文]. 上海: 复旦大学, 2014.