The Role of EZH2 in Ocular Diseases: A Narrative Review

References

• Varma R , VajaranantTS , BurkemperBet al. Visual impairment and blindness in adults in the United States: demographic and geographic variations from 2015 to 2050. JAMA Ophthalmol.134(7), 802–809 (2016).
   PubMed Web of Science ®Google Scholar
• Wang L , ZhuZ , ScheetzJ , HeM. Visual impairment and ten-year mortality: the Liwan Eye Study. Eye35(8), 2173–2179 (2021).
   PubMed Web of Science ®Google Scholar
• Berger SL , KouzaridesT , ShiekhattarR , ShilatifardA. An operational definition of epigenetics. Genes Dev.23(7), 781–783 (2009).
   PubMed Web of Science ®Google Scholar
• Rodenhiser D , MannM. Epigenetics and human disease: translating basic biology into clinical applications. CMAJ174(3), 341–348 (2006).
   PubMed Web of Science ®Google Scholar
• Vedschmidt SE , StagnerAM , EagleRCJr , HarocoposGJ , DouY , RaoRC. The targetable epigenetic tumor protein EZH2 is enriched in intraocular medulloepithelioma. Invest. Ophthalmol. Vis. Sci.57(14), 6242–6246 (2016).
   PubMed Web of Science ®Google Scholar
• Simon JA , LangeCA. Roles of the EZH2 histone methyltransferase in cancer epigenetics. Mutat. Res.647(1–2), 21–29 (2008).
   PubMed Web of Science ®Google Scholar
• Duan R , DuW , GuoW. EZH2: a novel target for cancer treatment. J. Hematol. Oncol.13(1), 104 (2020).
   PubMed Web of Science ®Google Scholar
• Zhang J , TaylorRJ , LaTorre Aet al. EZH2 maintains retinal progenitor proliferation, transcriptional integrity, and the timing of late differentiation. Dev. Biol.403(2), 128–138 (2015).
   PubMed Web of Science ®Google Scholar
• Jin B , ZhangP , ZouHet al. Verification of EZH2 as a druggable target in metastatic uveal melanoma. Mol. Cancer19(1), 52 (2020).
   PubMed Web of Science ®Google Scholar
• Cao J , PontesKC , HeijkantsRCet al. Overexpression of EZH2 in conjunctival melanoma offers a new therapeutic target. J. Pathol.245(4), 433–444 (2018).
   PubMed Web of Science ®Google Scholar
• Khan M , WaltersLL , LiQet al. Characterization and pharmacologic targeting of EZH2, a fetal retinal protein and epigenetic regulator, in human retinoblastoma. Lab. Invest.95(11), 1278–1290 (2015).
   PubMed Web of Science ®Google Scholar
• Liao K , CuiZ , ZengYet al. Inhibition of enhancer of zeste homolog 2 prevents corneal myofibroblast transformation in vitro. Exp. Eye Res.208, 108611 (2021).
   PubMed Web of Science ®Google Scholar
• Zhang L , WangL , HuXBet al. MYPT1/PP1-mediated EZH2 dephosphorylation at S21 promotes epithelial-mesenchymal transition in fibrosis through control of multiple families of genes. Adv. Sci. (Weinh.)9(14), e2105539 (2022).
   PubMedGoogle Scholar
• Thomas AA , FengB , ChakrabartiS. ANRIL: a regulator of VEGF in diabetic retinopathy. Invest. Ophthalmol. Vis. Sci.58(1), 470–480 (2017).
   PubMed Web of Science ®Google Scholar
• Di S , AnX , PangBet al. Yiqi Tongluo Fang could preventive and delayed development and formation of diabetic retinopathy through antioxidant and anti-inflammatory effects. Biomed. Pharmacother.148, 112254 (2022).
   PubMed Web of Science ®Google Scholar
• Mbefo M , BergerA , SchouweyKet al. Enhancer of zeste homolog 2 (EZH2) contributes to rod photoreceptor death process in several forms of retinal degeneration and its activity can serve as a biomarker for therapy efficacy. Int. J. Mol. Sci.22(17), 9331 (2021).
   PubMed Web of Science ®Google Scholar
• Wen X , DingT , LiFet al. Interruption of aberrant chromatin looping is required for regenerating RB1 function and suppressing tumorigenesis. Commun. Biol.5(1), 1036 (2022).
   PubMed Web of Science ®Google Scholar
• Duraisamy AJ , MishraM , KowluruRA. Crosstalk between histone and DNA methylation in regulation of retinal matrix metalloproteinase-9 in diabetes. Invest. Ophthalmol. Vis. Sci.58(14), 6440–6448 (2017).
   PubMed Web of Science ®Google Scholar
• Zeng J , ZhangJ , SunYet al. Targeting EZH2 for cancer therapy: from current progress to novel strategies. Eur. J. Med. Chem.238, 114419 (2022).
   PubMed Web of Science ®Google Scholar
• Völkel P , DupretB , LeBourhis X , AngrandPO. Diverse involvement of EZH2 in cancer epigenetics. Am. J. Transl. Res.7(2), 175–193 (2015).
   PubMed Web of Science ®Google Scholar
• Yamaguchi H , HungMC. Regulation and role of EZH2 in cancer. Cancer Res. Treat.46(3), 209–222 (2014).
   PubMed Web of Science ®Google Scholar
• Viré E , BrennerC , DeplusRet al. The polycomb group protein EZH2 directly controls DNA methylation. Nature439(7078), 871–874 (2006).
   PubMed Web of Science ®Google Scholar
• Kim E , KimM , WooDHet al. Phosphorylation of EZH2 activates STAT3 signaling via STAT3 methylation and promotes tumorigenicity of glioblastoma stem-like cells. Cancer Cell23(6), 839–852 (2013).
   PubMed Web of Science ®Google Scholar
• Fan T , JiangS , ChungNet al. EZH2-dependent suppression of a cellular senescence phenotype in melanoma cells by inhibition of p21/CDKN1A expression. Mol. Cancer Res.9(4), 418–429 (2011).
   PubMed Web of Science ®Google Scholar
• Hernandez AJ , ZovoilisA , Cifuentes-RojasC , HanL , BujisicB , LeeJT. B2 and ALU retrotransposons are self-cleaving ribozymes whose activity is enhanced by EZH2. Proc. Natl Acad. Sci. USA117(1), 415–425 (2020).
   PubMed Web of Science ®Google Scholar
• Tabbal H , SeptierA , MathieuMet al. EZH2 cooperates with E2F1 to stimulate expression of genes involved in adrenocortical carcinoma aggressiveness. Br. J. Cancer121(5), 384–394 (2019).
   PubMed Web of Science ®Google Scholar
• Rao RC , TchedreKT , MalikMTet al. Dynamic patterns of histone lysine methylation in the developing retina. Invest. Ophthalmol. Vis. Sci.51(12), 6784–6792 (2010).
   PubMed Web of Science ®Google Scholar
• Rapicavoli NA , PothEM , ZhuH , BlackshawS. The long noncoding RNA Six3OS acts in trans to regulate retinal development by modulating Six3 activity. Neural Dev.6, 32 (2011).
   PubMed Web of Science ®Google Scholar
• Aldiri I , MooreKB , HutchesonDA , ZhangJ , VetterML. Polycomb repressive complex PRC2 regulates Xenopus retina development downstream of Wnt/β-catenin signaling. Development140(14), 2867–2878 (2013).
   PubMed Web of Science ®Google Scholar
• Iida A , IwagawaT , KuribayashiHet al. Histone demethylase JMJD3 is required for the development of subsets of retinal bipolar cells. Proc. Natl Acad. Sci. USA111(10), 3751–3756 (2014).
   PubMed Web of Science ®Google Scholar
• Iida A , IwagawaT , BabaYet al. Roles of histone H3K27 trimethylase Ezh2 in retinal proliferation and differentiation. Dev. Neurobiol.75(9), 947–960 (2015).
   PubMed Web of Science ®Google Scholar
• Watanabe S , MurakamiA. Regulation of retinal development via the epigenetic modification of histone H3. Adv. Exp. Med. Biol.854, 635–641 (2016).
   PubMed Web of Science ®Google Scholar
• Fujimura N , KuzelovaA , EbertAet al. Polycomb repression complex 2 is required for the maintenance of retinal progenitor cells and balanced retinal differentiation. Dev. Biol.433(1), 47–60 (2018).
   PubMed Web of Science ®Google Scholar
• Andrews D , OlivieroG , DeChiara Let al. Unravelling the transcriptional responses of TGF-β: Smad3 and EZH2 constitute a regulatory switch that controls neuroretinal epithelial cell fate specification. FASEB J.33(5), 6667–6681 (2019).
   PubMed Web of Science ®Google Scholar
• Ben-Yosef T . Inherited retinal diseases. Int. J. Mol. Sci.23(21), 13467 (2022).
   PubMed Web of Science ®Google Scholar
• Zheng S , XiaoL , LiuYet al. DZNep inhibits H3K27me3 deposition and delays retinal degeneration in the rd1 mice. Cell Death Dis.9(3), 310 (2018).
   PubMedGoogle Scholar
• Ueno K , IwagawaT , KuribayashiHet al. Transition of differential histone H3 methylation in photoreceptors and other retinal cells during retinal differentiation. Sci. Rep.6, 29264 (2016).
   PubMed Web of Science ®Google Scholar
• Yan N , ChengL , ChoKet al. Postnatal onset of retinal degeneration by loss of embryonic Ezh2 repression of Six1. Sci. Rep.6, 33887 (2016).
   PubMed Web of Science ®Google Scholar
• Italiano A , SoriaJC , ToulmondeMet al. Tazemetostat, an EZH2 inhibitor, in relapsed or refractory B-cell non-Hodgkin lymphoma and advanced solid tumours: a first-in-human, open-label, phase 1 study. Lancet Oncol.19(5), 649–659 (2018).
   PubMed Web of Science ®Google Scholar
• Morschhauser F , TillyH , ChaidosAet al. Tazemetostat for patients with relapsed or refractory follicular lymphoma: an open-label, single-arm, multicentre, phase 2 trial. Lancet Oncol.21(11), 1433–1442 (2020).
   PubMed Web of Science ®Google Scholar
• Gounder M , SchöffskiP , JonesRLet al. Tazemetostat in advanced epithelioid sarcoma with loss of INI1/SMARCB1: an international, open-label, phase 2 basket study. Lancet Oncol.21(11), 1423–1432 (2020).
   PubMed Web of Science ®Google Scholar
• Song Y , LiuY , LiZMet al. SHR2554, an EZH2 inhibitor, in relapsed or refractory mature lymphoid neoplasms: a first-in-human, dose-escalation, dose-expansion, and clinical expansion phase 1 trial. Lancet Haematol.9(7), e493–e503 (2022).
   PubMed Web of Science ®Google Scholar
• Izutsu K , AndoK , NishikoriMet al. Phase II study of tazemetostat for relapsed or refractory B-cell non-Hodgkin lymphoma with EZH2 mutation in Japan. Cancer Sci.112(9), 3627–3635 (2021).
   PubMed Web of Science ®Google Scholar
• Vaswani RG , GehlingVS , DakinLAet al. Identification of (R)-N-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1H-indole-3-carboxamide (CPI-1205), a potent and selective inhibitor of histone methyltransferase EZH2, suitable for phase I clinical trials for B-cell lymphomas. J. Med. Chem.59(21), 9928–9941 (2016).
   PubMed Web of Science ®Google Scholar
• Yap TA , WinterJN , Giulino-RothLet al. Phase I study of the novel enhancer of zeste homolog 2 (EZH2) inhibitor GSK2816126 in patients with advanced hematologic and solid tumors. Clin. Cancer Res.25(24), 7331–7339 (2019).
   PubMed Web of Science ®Google Scholar
• Munakata W , ShirasugiY , TobinaiKet al. Phase 1 study of tazemetostat in Japanese patients with relapsed or refractory B-cell lymphoma. Cancer Sci.112(3), 1123–1131 (2021).
   PubMed Web of Science ®Google Scholar
• Zauderer MG , SzlosarekPW , LeMoulec Set al. EZH2 inhibitor tazemetostat in patients with relapsed or refractory, BAP1-inactivated malignant pleural mesothelioma: a multicentre, open-label, phase 2 study. Lancet Oncol.23(6), 758–767 (2022).
   PubMed Web of Science ®Google Scholar
• Lu Q , ZhaoN , ZhaG , WangH , TongQ , XinS. LncRNA HOXA11-AS exerts oncogenic functions by repressing p21 and miR-124 in uveal melanoma. DNA Cell Biol.36(10), 837–844 (2017).
   PubMed Web of Science ®Google Scholar
• Li Y , ZhangM , FengH , MahatiS. The tumorigenic properties of EZH2 are mediated by miR-26a in uveal melanoma. Front. Mol. Biosci.8, 713542 (2021).
   PubMed Web of Science ®Google Scholar
• Zhang J , LiuG , JinHet al. MicroRNA-137 targets EZH2 to exert suppressive functions in uveal melanoma via regulation of Wnt/β-catenin signaling and epithelial-to-mesenchymal transition. J. BUON26(1), 173–181 (2021).
   PubMed Web of Science ®Google Scholar
• Hou C , XiaoL , RenXet al. EZH2-mediated H3K27me3 is a predictive biomarker and therapeutic target in uveal melanoma. Front. Genet.13, 1013475 (2022).
   PubMed Web of Science ®Google Scholar
• Zhao Y , ChengY , QuY. The role of EZH2 as a potential therapeutic target in retinoblastoma. Exp. Eye Res.227, 109389 (2023).
   PubMed Web of Science ®Google Scholar
• Singh AD , TurellME , TophamAK. Uveal melanoma: trends in incidence, treatment, and survival. Ophthalmology118(9), 1881–1885 (2011).
   PubMed Web of Science ®Google Scholar
• Smit KN , JagerMJ , DeKlein A , KiliçE. Uveal melanoma: towards a molecular understanding. Prog. Retin. Eye Res.75, 100800 (2020).
   PubMed Web of Science ®Google Scholar
• Cheng Y , LiY , HuangX , WeiW , QuY. Expression of EZH2 in uveal melanomas patients and associations with prognosis. Oncotarget8(44), 76423–76431 (2017).
   PubMedGoogle Scholar
• Wu X , YuanY , MaR , XuB , ZhangR. lncRNA SNHG7 affects malignant tumor behaviors through downregulation of EZH2 in uveal melanoma cell lines. Oncol. Lett.19(2), 1505–1515 (2020).
   PubMed Web of Science ®Google Scholar
• Chen X , HeD , DongXDet al. MicroRNA-124a is epigenetically regulated and acts as a tumor suppressor by controlling multiple targets in uveal melanoma. Invest. Ophthalmol. Vis. Sci.54(3), 2248–2256 (2013).
   PubMed Web of Science ®Google Scholar
• Rossi E , SchinzariG , MaioranoBAet al. Conjunctival melanoma: genetic and epigenetic insights of a distinct type of melanoma. Int J Mol Sci20(21), 5447 (2019).
   PubMed Web of Science ®Google Scholar
• Mudhar HS , SalviSS , PissalouxD , DeLa Fouchardiere A. Single time frame overview of the genetic changes in conjunctival melanoma from intraepithelial disease to invasive melanoma: a study of 4 exenteration specimens illustrating the potential role of cyclin D1. Ocul. Oncol. Pathol.8(1), 52–63 (2022).
   PubMed Web of Science ®Google Scholar
• Kaewkhaw R , RojanapornD. Retinoblastoma: etiology, modeling, and treatment. Cancers (Basel)12(8), 2304 (2020).
   PubMed Web of Science ®Google Scholar
• Fabian ID , OnadimZ , KaraaEet al. The management of retinoblastoma. Oncogene37(12), 1551–1560 (2018).
   PubMed Web of Science ®Google Scholar
• Dimaras H , CorsonTW , CobrinikDet al. Retinoblastoma. Nat. Rev. Dis. Primers1, 15021 (2015).
   PubMed Web of Science ®Google Scholar
• Ishak CA , MarshallAE , PassosDTet al. An RB–EZH2 complex mediates silencing of repetitive DNA sequences. Mol. Cell64(6), 1074–1087 (2016).
   PubMed Web of Science ®Google Scholar
• Lei Q , ShenF , WuJ , ZhangW , WangJ , ZhangL. MiR-101, downregulated in retinoblastoma, functions as a tumor suppressor in human retinoblastoma cells by targeting EZH2. Oncol. Rep.32(1), 261–269 (2014).
   PubMed Web of Science ®Google Scholar
• Saunders T , MargoCE. Intraocular medulloepithelioma. Arch. Pathol. Lab. Med.136(2), 212–216 (2012).
   PubMed Web of Science ®Google Scholar
• Edward DP , AlkatanH , RafiqQet al. MicroRNA profiling in intraocular medulloepitheliomas. PLOS ONE10(3), e0121706 (2015).
   PubMed Web of Science ®Google Scholar
• Fini ME . Keratocyte and fibroblast phenotypes in the repairing cornea. Prog. Retin. Eye Res.18(4), 529–551 (1999).
   PubMed Web of Science ®Google Scholar
• Wilson SE . Corneal wound healing. Exp. Eye Res.197, 108089 (2020).
   PubMed Web of Science ®Google Scholar
• Ljubimov AV , SaghizadehM. Progress in corneal wound healing. Prog. Retin. Eye Res.49, 17–45 (2015).
   PubMed Web of Science ®Google Scholar
• Kamil S , MohanRR. Corneal stromal wound healing: major regulators and therapeutic targets. Ocul. Surf.19, 290–306 (2021).
   PubMed Web of Science ®Google Scholar
• Zhao X , SongW , ChenY , LiuS , RenL. Collagen-based materials combined with microRNA for repairing cornea wounds and inhibiting scar formation. Biomater. Sci.7(1), 51–62 (2018).
   PubMed Web of Science ®Google Scholar
• Shu DY , LovicuFJ. Myofibroblast transdifferentiation: the dark force in ocular wound healing and fibrosis. Prog. Retin. Eye Res.60, 44–65 (2017).
   PubMed Web of Science ®Google Scholar
• Myrna KE , PotSA , MurphyCJ. Meet the corneal myofibroblast: the role of myofibroblast transformation in corneal wound healing and pathology. Vet. Ophthalmol.12(Suppl. 1), 25–27 (2009).
   PubMedGoogle Scholar
• Wilson SE . Corneal myofibroblasts and fibrosis. Exp. Eye Res.201, 108272 (2020).
   PubMed Web of Science ®Google Scholar
• Wan S-S , PanY-M , YangW-J , RaoZ-Q , YangY-N. Inhibition of EZH2 alleviates angiogenesis in a model of corneal neovascularization by blocking FoxO3a-mediated oxidative stress. FASEB J.34(8), 10168–10181 (2020).
   PubMed Web of Science ®Google Scholar
• Thompson J , LakhaniN. Cataracts. Prim. Care42(3), 409–423 (2015).
   PubMed Web of Science ®Google Scholar
• Liu YC , WilkinsM , KimT , MalyuginB , MehtaJS. Cataracts. Lancet390(10094), 600–612 (2017).
   PubMed Web of Science ®Google Scholar
• Gao M , HuangY , WangLet al. HSF4 regulates lens fiber cell differentiation by activating p53 and its downstream regulators. Cell Death Dis.8(10), e3082 (2017).
   PubMedGoogle Scholar
• Mou L , XuJY , LiWet al. Identification of vimentin as a novel target of HSF4 in lens development and cataract by proteomic analysis. Invest. Ophthalmol. Vis. Sci.51(1), 396–404 (2010).
   PubMed Web of Science ®Google Scholar
• Cui X , DuC , WanSet al. Deficiency of heat shock factor 4 promotes lens epithelial cell senescence through upregulating p21cip1 expression. Biochim. Biophys. Acta Mol. Basis Dis.1867(11), 166233 (2021).
   PubMed Web of Science ®Google Scholar
• Lee CM , AfshariNA. The global state of cataract blindness. Curr. Opin. Ophthalmol.28(1), 98–103 (2017).
   PubMed Web of Science ®Google Scholar
• Wormstone IM , WangL , LiuCS. Posterior capsule opacification. Exp. Eye Res.88(2), 257–269 (2009).
   PubMed Web of Science ®Google Scholar
• Wormstone IM , EldredJA. Experimental models for posterior capsule opacification research. Exp. Eye Res.142, 2–12 (2016).
   PubMed Web of Science ®Google Scholar
• Wormstone IM , WormstoneYM , SmithAJO , EldredJA. Posterior capsule opacification: what’s in the bag?Prog. Retin. Eye Res.82, 100905 (2021).
   PubMed Web of Science ®Google Scholar
• Dong N , XuB , XuJ. EGF-Mediated overexpression of Myc attenuates miR-26b by recruiting HDAC3 to induce epithelial–mesenchymal transition of lens epithelial cells. Biomed. Res. Int.2018, 7148023 (2018).
   PubMed Web of Science ®Google Scholar
• Imaizumi T , KurosakaD , TanakaU , SakaiD , FukudaK , SanbeA. Topical administration of a ROCK inhibitor prevents anterior subcapsular cataract induced by UV-B irradiation. Exp. Eye Res.181, 145–149 (2019).
   PubMed Web of Science ®Google Scholar
• Almasieh M , WilsonAM , MorquetteB , CuevaVargas JL , DiPolo A. The molecular basis of retinal ganglion cell death in glaucoma. Prog. Retin. Eye Res.31(2), 152–181 (2012).
   PubMed Web of Science ®Google Scholar
• Fry LE , FahyE , ChrysostomouVet al. The coma in glaucoma: retinal ganglion cell dysfunction and recovery. Prog. Retin. Eye Res.65, 77–92 (2018).
   PubMed Web of Science ®Google Scholar
• Xiao L , HouC , ChengL , ZhengS , ZhaoL , YanN. DZNep protects against retinal ganglion cell death in an NMDA-induced mouse model of retinal degeneration. Exp. Eye Res.212, 108785 (2021).
   PubMed Web of Science ®Google Scholar
• Cheng L , WongLJ , YanNet al. Ezh2 does not mediate retinal ganglion cell homeostasis or their susceptibility to injury. PLOS ONE13(2), e0191853 (2018).
   PubMed Web of Science ®Google Scholar
• Zhou RR , LiHB , YouQSet al. Silencing of GAS5 alleviates glaucoma in rat models by reducing retinal ganglion cell apoptosis. Hum. Gene Ther.30(12), 1505–1519 (2019).
   PubMed Web of Science ®Google Scholar
• Zhang N , CaoW , HeX , XingY , YangN. Long non-coding RNAs in retinal ganglion cell apoptosis. Cell. Mol. Neurobiol.43(2), 561–574 (2023).
   PubMed Web of Science ®Google Scholar
• Kowluru RA , MohammadG , DosSantos JM , ZhongQ. Abrogation of MMP-9 gene protects against the development of retinopathy in diabetic mice by preventing mitochondrial damage. Diabetes60(11), 3023–3033 (2011).
   PubMed Web of Science ®Google Scholar
• Huang Y , YuSH , ZhenWXet al. Tanshinone I, a new EZH2 inhibitor restricts normal and malignant hematopoiesis through upregulation of MMP9 and ABCG2. Theranostics11(14), 6891–6904 (2021).
   PubMed Web of Science ®Google Scholar
• Delgado-Olguín P , DangLT , HeDet al. Ezh2-mediated repression of a transcriptional pathway upstream of Mmp9 maintains integrity of the developing vasculature. Development141(23), 4610–4617 (2014).
   PubMed Web of Science ®Google Scholar
• Song Z , WuW , ChenMet al. Long noncoding RNA ANRIL supports proliferation of adult T-cell leukemia cells through cooperation with EZH2. J. Virol.92(24), e00909–18 (2018).
   PubMed Web of Science ®Google Scholar
• Yang LH , DuP , LiuWet al. LncRNA ANRIL promotes multiple myeloma progression and bortezomib resistance by EZH2-mediated epigenetically silencing of PTEN. Neoplasma68(4), 788–797 (2021).
   PubMed Web of Science ®Google Scholar
• Witmer AN , VrensenGF , Van NoordenCJ , SchlingemannRO. Vascular endothelial growth factors and angiogenesis in eye disease. Prog. Retin. Eye Res.22(1), 1–29 (2003).
   PubMed Web of Science ®Google Scholar
• Osaadon P , FaganXJ , LifshitzT , LevyJ. A review of anti-VEGF agents for proliferative diabetic retinopathy. Eye28(5), 510–520 (2014).
   PubMed Web of Science ®Google Scholar
• Yang Y , LiuY , LiYet al. MicroRNA-15b targets VEGF and inhibits angiogenesis in proliferative diabetic retinopathy. J. Clin. Endocrinol. Metab.105(11), 3404–3415 (2020).
   PubMed Web of Science ®Google Scholar
• Wong TY , CheungCM , LarsenM , SharmaS , SimóR. Diabetic retinopathy. Nat. Rev. Dis. Primers2, 16012 (2016).
   PubMed Web of Science ®Google Scholar
• Ruiz MA , FengB , ChakrabartiS. Polycomb repressive complex 2 regulates miR-200b in retinal endothelial cells: potential relevance in diabetic retinopathy. PLOS ONE10(4), e0123987 (2015).
   PubMed Web of Science ®Google Scholar
• Biswas S , ThomasAA , FengBet al. MALAT1 and HOTAIR – key epigenetic regulators in diabetic retinopathy. Diabetes67(Suppl. 1), 240-OR (2018).
   Google Scholar
• Di S , AnX , PangBet al. Yiqi Tongluo Fang could preventive and delayed development and formation of diabetic retinopathy through antioxidant and anti-inflammatory effects. Biomed. Pharmacother.148, 112254 (2022).
   PubMed Web of Science ®Google Scholar
• Olivares AM , JelcickAS , ReineckeJet al. Multimodal regulation orchestrates normal and complex disease states in the retina. Sci. Rep.7(1), 690 (2017).
   PubMedGoogle Scholar
• Peng Y , LiaoK , TanFet al. Suppression of EZH2 inhibits TGF-β1-induced EMT in human retinal pigment epithelial cells. Exp. Eye Res.222, 109158 (2022).
   PubMed Web of Science ®Google Scholar
• Lee HE , AyarpadikannanS , KimHS. Role of transposable elements in genomic rearrangement, evolution, gene regulation and epigenetics in primates. Genes Genet. Syst.90(5), 245–257 (2015).
   PubMed Web of Science ®Google Scholar
• Kaneko H , DridiS , TaralloVet al. DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration. Nature471(7338), 325–330 (2011).
   PubMed Web of Science ®Google Scholar
• Tarallo V , HiranoY , GelfandBDet al. DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88. Cell149(4), 847–859 (2012).
   PubMed Web of Science ®Google Scholar
• Gelfand BD , WrightCB , KimYet al. Iron toxicity in the retina requires Alu RNA and the NLRP3 inflammasome. Cell Rep.11(11), 1686–1693 (2015).
   PubMed Web of Science ®Google Scholar
• Zhu S , LiuM , ZhuF , YuX , WenJ , LiC. Targeting EZH2 prevents the occurrence and mitigates the development of Sjögren’s syndrome in mice. Int. Immunopharmacol.110, 109073 (2022).
   PubMed Web of Science ®Google Scholar
• He C , YangY , ChenZet al. EZH2 promotes T follicular helper cell differentiation through enhancing STAT3 phosphorylation in patients with primary Sjögren’s syndrome. Front. Immunol.13, 922871 (2022).
   PubMed Web of Science ®Google Scholar
• Katoh M . Mutation spectra of histone methyltransferases with canonical SET domains and EZH2-targeted therapy. Epigenomics8(2), 285–305 (2016).
   PubMed Web of Science ®Google Scholar