Research status of mTORC1 pathway involved in the progression of myopia

doi:10.3877/cma.j.issn.2095-2007.2022.04.011

Abstract

Abstract:

In recent years, the incidence rate of myopia has increased significantly, especially the development of myopia diopter and the occurrence and development of its complications have aroused widespread concern in the industry and society. To explore the pathophysiological mechanism of myopia has become the focus, and also is the key breakthrough point in its prevention and control. The existing literature show that the progress of myopia involves multiple pathways. Rapamycin target protein complex 1 (mTORC1) plays an important role in regulating the growth and metabolism of eukaryotic cells. Relevant studies have found that mTORC1 is involved in regulating the progress of myopia. In this article, the research status of mTORC1 pathway in the development of myopia were reviewed.

Key words: Myopia, Epidermal growth factor receptor, Mechanistic target of rapamycin complex1

Ruiheng Zhang, Li Dong, Wenbin Wei. Research status of mTORC1 pathway involved in the progression of myopia[J]. Chinese Journal of Ophthalmologic Medicine(Electronic Edition), 2022, 12(04): 247-251.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhykyxzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-2007.2022.04.011

https://zhykyxzz.cma-cmc.com.cn/EN/Y2022/V12/I04/247

References 56

[1]	Xu L, Wang Y, Li Y, et al. Causes of blindness and visual impairment in urban and rural areas in Beijing: the Beijing Eye Study[J]. Ophthalmology, 2006, 113(7): e1131－e1134.
[2]	Morgan IG, French AN, Ashby RS, et al. The epidemics of myopia: Aetiology and prevention[J]. Prog Retin Eye Res, 2018, 62: 134－149.
[3]	徐玉珊，张丰菊. 眼部信号转导在近视发病机制中的作用[J]. 国际眼科纵览，2020, 44(5)：318－323.
[4]	Saxton RA, Sabatini DM. mTOR Signaling in Growth, Metabolism, and Disease[J]. Cell, 2017, 168(6): 960－976.
[5]	Qin J, Wang Z, Hoogeveen－Westerveld M, et al. Structural Basis of the Interaction between Tuberous Sclerosis Complex 1 (TSC1) and Tre2－Bub2－Cdc16 Domain Family Member 7 (TBC1D7)[J]. J Biol Chem, 2016, 291(16): 8591－8601.
[6]	Dibble CC, Cantley LC. Regulation of mTORC1 by PI3K signaling[J]. Trends Cell Biol, 2015, 25(9): 545－555.
[7]	Liu P, Gan W, Chin YR, et al. PtdIns(3，4，5)P3－Dependent Activation of the mTORC2 Kinase Complex[J]. Cancer Discov, 2015, 5(11): 1194－1209.
[8]	Henske EP, Jóžwiak S, Kingswood JC, et al. Tuberous sclerosis complex[J]. Nat Rev Dis Primers, 2016, 2(1): 16035.
[9]	Rowley SA, O'callaghan FJ, Osborne JP. Ophthalmic manifestations of tuberous sclerosis: a population based study[J]. Br J Ophthalmol, 2001, 85(4): 420－423.
[10]	Gai Z, Chu W, Deng W, et al. Structure of the TBC1D7－TSC1 complex reveals that TBC1D7 stabilizes dimerization of the TSC1 C－terminal coiled coil region[J]. J Mol Cell Biol, 2016, 8(5): 411－425.
[11]	Dibble CC, Elis W, Menon S, et al. TBC1D7 is a third subunit of the TSC1－TSC2 complex upstream of mTORC1[J]. Mol cell, 2012, 47(4): 535－546.
[12]	Alfaiz AA, Micale L, Mandriani B, et al. TBC1D7 mutations are associated with intellectual disability, macrocrania, patellar dislocation, and celiac disease[J]. Hum Mutat, 2014, 35(4): 447－451.
[13]	Capo－Chichi JM, Tcherkezian J, Hamdan FF, et al. Disruption of TBC1D7, a subunit of the TSC1－TSC2 protein complex, in intellectual disability and megalencephaly[J]. J Med Genet, 2013, 50(11): 740－744.
[14]	Tam V, Patel N, Turcotte M, et al. Benefits and limitations of genome－wide association studies[J]. Nat Rev Genet, 2019, 20(8): 467－484.
[15]	Li X, Long J, Liu Y, et al. Association of MTOR and PDGFRA gene polymorphisms with different degrees of myopia severity[J]. Exp Eye Res, 2022, 217: 108962.
[16]	Yuan XL, Zhang R, Zheng Y, et al. Corneal curvature－associated variant differentiates mild myopia from high myopia in Han Chinese population[J]. Ophthalmic Genet, 2021, 42(4): 446－457.
[17]	Kovacs E, Zorn JA, Huang Y, et al. A structural perspective on the regulation of the epidermal growth factor receptor[J]. Annu Rev Biochem, 2015, 84: 739－764.
[18]	Chen H, Liu B, Neufeld AH. Epidermal growth factor receptor in adult retinal neurons of rat, mouse, and human[J]. J Comp Neurol, 2007, 500(2): 299－310.
[19]	Jonas JB, Dong L, Da Chen S, et al. Intraocular epidermal growth factor concentration, axial length, and high axial myopia[J]. Graefes Arch Clin Exp Ophthalmol, 2021, 259(11): 3229－3234.
[20]	Dong L, Shi XH, Li YF, et al. Blockade of epidermal growth factor and its receptor and axial elongation in experimental myopia[J]. The FASEB J, 2020, 34(10): 13654－13670.
[21]	Fan Q, Verhoeven VJM, Wojciechowski R, et al. Meta－analysis of gene－environment－wide association scans accounting for education level identifies additional loci for refractive error[J]. Nat Commun, 2016, 7: 11008.
[22]	Berasain C, Avila MA. Amphiregulin[J]. Semin Cell Dev Biol, 2014, 28: 31－41.
[23]	Dong L, Shi XH, Kang YK, et al. Amphiregulin and ocular axial length[J]. Acta Ophthalmol, 2019, 97(3): e460－e470.
[24]	Jiang WJ, Song HX, Li SY, et al. Amphiregulin Antibody and Reduction of Axial Elongation in Experimental Myopia[J]. EBioMedicine, 2017, 17: 134－144.
[25]	Wee P, Wang Z. Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways[J]. Cancers, 2017, 9(5): 52.
[26]	Wei CC, Kung YJ, Chen CS, et al. Allergic Conjunctivitis－induced Retinal Inflammation Promotes Myopia Progression[J]. EBioMedicine, 2018, 28: 274－286.
[27]	He M, Xiang F, Zeng Y, et al. Effect of Time Spent Outdoors at School on the Development of Myopia Among Children in China: A Randomized Clinical Trial[J]. JAMA, 2015, 314(11): 1142－1148.
[28]	Mimura T, Yamagami S, Usui T, et al. Relationship between myopia and allergen－specific serum IgE levels in patients with allergic conjunctivitis[J]. Clin Exp Ophthalmol, 2009, 37(7): 670－677.
[29]	Shafer BM, Qiu M, Rapuano CJ, et al. Association Between Hay Fever and High Myopia in United States Adolescents and Adults[J]. Eye Contact Lens, 2017, 43(3): 186－191.
[30]	Xue M, Ke Y, Ren X, et al. Proteomic analysis of aqueous humor in patients with pathologic myopia[J]. J Proteomics, 2021, 234: 104088.
[31]	Zeng L, Li X, Liu J, et al. RNA－Seq Analysis Reveals an Essential Role of the Tyrosine Metabolic Pathway and Inflammation in Myopia－Induced Retinal Degeneration in Guinea Pigs[J]. Int J Mol Sci, 2021, 22(22): 12598.
[32]	Tien PT, Lin CH, Chen CS, et al. Diacerein Inhibits Myopia Progression through Lowering Inflammation in Retinal Pigment Epithelial Cell[J]. Mediators Inflamm, 2021: 6660640.
[33]	Mérida S, Villar V M, Navea A, et al. Imbalance Between Oxidative Stress and Growth Factors in Human High Myopia[J]. Front Physiol, 2020, 11: 463.
[34]	Yu FJ, Lam TC, Sze A YH, et al. Alteration of retinal metabolism and oxidative stress may implicate myopic eye growth: Evidence from discovery and targeted proteomics in an animal model[J]. J Proteomics, 2020, 221: 103684.
[35]	Feng L, Ju M, Lee KYV, et al. A Proinflammatory Function of Toll－Like Receptor 2 in the Retinal Pigment Epithelium as a Novel Target for Reducing Choroidal Neovascularization in Age－Related Macular Degeneration[J]. Am J Pathol, 2017, 187(10): 2208－2221.
[36]	Huang J, Gu S, Chen M, et al. Abnormal mTORC1 signaling leads to retinal pigment epithelium degeneration[J]. Theranostics, 2019, 9(4): 1170－1180.
[37]	Summers JA, Martinez E. Visually induced changes in cytokine production in the chick choroid[J]. eLife, 2021, 10: e70608.
[38]	Wei WB, Xu L, Jonas JB, et al. Subfoveal choroidal thickness: the Beijing Eye Study[J]. Ophthalmology, 2013, 120(1): 175－180.
[39]	Jin P, Zou H, Zhu J, et al. Choroidal and Retinal Thickness in Children With Different Refractive Status Measured by Swept－Source Optical Coherence Tomography[J]. Am J Ophthalmol, 2016, 168: 164－176.
[40]	Wakabayashi T, Ikuno Y. Choroidal filling delay in choroidal neovascularisation due to pathological myopia[J]. Br J Ophthalmol, 2010, 94(5): 611－615.
[41]	Al－Sheikh M, Phasukkijwatana N, Dolz－Marco R, et al. Quantitative OCT Angiography of the Retinal Microvasculature and the Choriocapillaris in Myopic Eyes[J]. Invest Ophthalmol Vis Sci, 2017, 58(4): 2063－2069.
[42]	Wu H, Zhang G, Shen M, et al. Assessment of Choroidal Vascularity and Choriocapillaris Blood Perfusion in Anisomyopic Adults by SS－OCT/OCTA[J]. Invest Ophthalmol Vis Sci, 2021, 62(1): 8.
[43]	Agrawal R, Gupta P, Tan KA, et al. Choroidal vascularity index as a measure of vascular status of the choroid: Measurements in healthy eyes from a population－based study[J]. Sci Rep, 2016, 6: 21090.
[44]	Zhang S, Zhang G, Zhou X, et al. Changes in Choroidal Thickness and Choroidal Blood Perfusion in Guinea Pig Myopia[J]. Invest Ophthalmol Vis Sci, 2019, 60(8): 3074－3083.
[45]	Zhou X, Zhang S, Zhang G, et al. Increased Choroidal Blood Perfusion Can Inhibit Form Deprivation Myopia in Guinea Pigs[J]. Invest Ophthalmol Vis Sci, 2020, 61(13): 25.
[46]	Wei Q, Zhuang X, Fan J, et al. Proinflammatory and angiogenesis－related cytokines in vitreous samples of highly myopic patients[J]. Cytokine, 2021, 137: 155308.
[47]	Zhao F, Zhang D, Zhou Q, et al. Scleral HIF－1α is a prominent regulatory candidate for genetic and environmental interactions in human myopia pathogenesis[J]. EBioMedicine, 2020, 57: 102878.
[48]	Wu H, Chen W, Zhao F, et al. Scleral hypoxia is a target for myopia control[J]. Proc Natl Acad Sci U S A, 2018, 115(30): e7091－e7100.
[49]	Dodd KM, Yang J, Shen MH, et al. mTORC1 drives HIF－1α and VEGF－A signalling via multiple mechanisms involving 4E－BP1, S6K1 and STAT3[J]. Oncogene, 2015, 34(17): 2239－2250.
[50]	Ruiz－Medrano J, Montero JA, Flores－Moreno I, et al. Myopic maculopathy: Current status and proposal for a new classification and grading system (ATN)[J]. Prog Retin Eye Res, 2019, 69: 80－115.
[51]	Harimoto A, Obata R, Yamamoto M, et al. Retinal pigment epithelium melanin distribution estimated by polarisation entropy and its association with retinal sensitivity in patients with high myopia[J]. Br J Ophthalmol, 2022，106(10): 1457－1462.
[52]	Du R, Fang Y, Jonas JB, et al. Clinical features of patchy chorioretinal atrophy In pathologic myopia[J]. Retina (Philadelphia, Pa), 2020, 40(5): 951－959.
[53]	Go YM, Zhang J, Fernandes J, et al. MTOR－initiated metabolic switch and degeneration in the retinal pigment epithelium[J]．FASEB J, 2020, 34(9): 12502－12520.
[54]	He L, Gomes AP, Wang X, et al. mTORC1 Promotes Metabolic Reprogramming by the Suppression of GSK3－Dependent Foxk1 Phosphorylation[J]. Mol cell, 2018, 70(5): 949－960.
[55]	Liu NN, Zhao N, Cai N. Suppression of the proliferation of hypoxia－Induced retinal pigment epithelial cell by rapamycin through the /mTOR/HIF－1α/VEGF/ signaling[J]. IUBMB life, 2015, 67(6): 446－452.
[56]	Wang C, Ma J, Xu M, et al. mTORC1 signaling pathway regulates macrophages in choroidal neovascularization[J]. Mol Immunol, 2020, 121: 72－80.

Please choose a citation manager

Content to export