Abstract
The critical role of epigenetic modification of histones in maintaining the normal function of the nervous system has attracted increasing attention. Among these modifications, the level of histone acetylation, modulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), is essential in regulating gene expression. In recent years, the research progress on the function of HDACs in retinal development and disease has advanced remarkably, while that regarding HATs remains to be investigated. Here, we overview the roles of HATs and HDACs in regulating the development of diverse retinal cells, including retinal progenitor cells, photoreceptor cells, bipolar cells, ganglion cells, and Müller glial cells. The effects of HATs and HDACs on the progression of various retinal diseases are also discussed with the highlight of the proof-of-concept research regarding the application of available HDAC inhibitors in treating retinal diseases.
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References
Chen X, Wang S, Xu H, Pereira JD, Hatzistergos KE, Saur D, Seidler B, Hare JM, Perrella MA, Yin ZQ, Liu X (2017) Evidence for a retinal progenitor cell in the postnatal and adult mouse. Stem Cell Res 23:20–32
Iwagawa T, Watanabe S (2019) Molecular mechanisms of H3K27me3 and H3K4me3 in retinal development. Neurosci Res 138:43–48
Masland RH (2012) The neuronal organization of the retina. Neuron 76(2):266–280
Danjo Y, Shinozaki Y, Natsubori A, Kubota Y, Kashiwagi K, Tanaka KF, Koizumi S (2022) The Mlc1 promoter directs Muller cell-specific gene expression in the retina. Transl Vis Sci Technol 11(1):25
Diacou R, Nandigrami P, Fiser A, Liu W, Ashery-Padan R, Cvekl A (2022) Cell fate decisions, transcription factors and signaling during early retinal development. Prog Retin Eye Res 91:101093
O'Hara-Wright M, Gonzalez-Cordero A (2020) Retinal organoids: a window into human retinal development. Development 147(24)
Bassett EA, Wallace VA (2012) Cell fate determination in the vertebrate retina. Trends Neurosci 35(9):565–573
Aldiri I, Xu B, Wang L, Chen X, Hiler D, Griffiths L, Valentine M, Shirinifard A, Thiagarajan S, Sablauer A, Barabas ME, Zhang J, Johnson D, Frase S, Zhou X, Easton J, Zhang J, Mardis ER, Wilson RK et al (2017) The dynamic epigenetic landscape of the retina during development, reprogramming, and tumorigenesis. Neuron 94(3):550–568.e10
Basinski BW, Balikov DA, Aksu M, Li Q, Rao RC (2021) Ubiquitous chromatin modifiers in congenital retinal diseases: implications for disease modeling and regenerative medicine. Trends Mol Med 27(4):365–378
Wu MS, Li XJ, Liu CY, Xu Q, Huang JQ, Gu S, Chen JX (2022) Effects of histone modification in major depressive disorder. Curr Neuropharmacol 20(7):1261–1277
Zentner GE, Henikoff S (2013) Regulation of nucleosome dynamics by histone modifications. Nat Struct Mol Biol 20(3):259–266
Berner AK, Kleinman ME (2016) Therapeutic approaches to histone reprogramming in retinal degeneration. Adv Exp Med Biol 854:39–44
Yu D, Tang Q, Liu L, He D, Wang L, Zhou X (2022) HDAC3 Inhibition alleviates high-glucose-induced retinal ganglion cell death through inhibiting inflammasome activation. Biomed Res Int 2022:4164824
Zhang X, Zhang BW, Xiang L, Wu H, Alexander SUPITAS, Zhou P, Dai MZY, Wang X, Xiong W, Zhang Y, Jin ZB, Deng LW (2022) MLL5 is involved in retinal photoreceptor maturation through facilitating CRX-mediated photoreceptor gene transactivation. iScience 25(4):104058
Gupta S, Sharma P, Chaudhary M, Premraj S, Kaur S, Vijayan V, Arun MG, Prasad NG, Ramachandran R (2023) Pten associates with important gene regulatory network to fine-tune Muller glia-mediated zebrafish retina regeneration. Glia 71:259–283
Barnes CE, English DM, Cowley SM (2019) Acetylation & Co: an expanding repertoire of histone acylations regulates chromatin and transcription. Essays Biochem 63(1):97–107. https://doi.org/10.1042/EBC20180061
Shvedunova M, Akhtar A (2022) Modulation of cellular processes by histone and non-histone protein acetylation. Nat Rev Mol Cell Biol 23(5):329–349
Haberland M, Montgomery RL, Olson EN (2009) The many roles of histone deacetylases in development and physiology: implications for disease and therapy. Nat Rev Genet 10(1):32–42
Yang XJ, Gregoire S (2005) Class II histone deacetylases: from sequence to function, regulation, and clinical implication. Mol Cell Biol 25(8):2873–2884
Park SY, Kim JS (2020) A short guide to histone deacetylases including recent progress on class II enzymes. Exp Mol Med 52(2):204–212
Schlüter A, Aksan B, Fioravanti R, Valente S, Mai A, Mauceri D (2019) Histone deacetylases contribute to excitotoxicity-triggered degeneration of retinal ganglion cells in vivo. Mol Neurobiol 56(12):8018–8034
Anderson KW, Chen J, Wang M, Mast N, Pikuleva IA, Turko IV (2015) Quantification of histone deacetylase isoforms in human frontal cortex, human retina, and mouse brain. PLoS One 10(5):e0126592
Zaidi SAH, Thakore N, Singh S, Guzman W, Mehrotra S, Gangaraju V, Husain S (2020) Histone deacetylases regulation by delta-opioids in human optic nerve head astrocytes. Invest Ophthalmol Vis Sci 61(11):17
Xiao W, Chen X, Liu X, Luo L, Ye S, Liu Y (2014) Trichostatin A, a histone deacetylase inhibitor, suppresses proliferation and epithelial-mesenchymal transition in retinal pigment epithelium cells. J Cell Mol Med 18(4):646–655
Chuang DM, Leng Y, Marinova Z, Kim HJ, Chiu CT (2009) Multiple roles of HDAC inhibition in neurodegenerative conditions. Trends Neurosci 32(11):591–601
Finnin MS, Donigian JR, Cohen A, Richon VM, Rifkind RA, Marks PA, Breslow R, Pavletich NP (1999) Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors. Nature 401(6749):188–193
Shahbazian MD, Grunstein M (2007) Functions of site-specific histone acetylation and deacetylation. Annu Rev Biochem 76:75–100
Martin BJE, Brind’Amour J, Kuzmin A, Jensen KN, Liu ZC, Lorincz M, Howe LAJ (2021) Transcription shapes genome-wide histone acetylation patterns. Nature. Communications 12(1)
Yamaguchi M, Tonou-Fujimori N, Komori A, Maeda R, Nojima Y, Li H, Okamoto H, Masai I (2005) Histone deacetylase 1 regulates retinal neurogenesis in zebrafish by suppressing Wnt and Notch signaling pathways. Development 132(13):3027–3043
Mitra S, Sharma P, Kaur S, Khursheed MA, Gupta S, Chaudhary M, Kurup AJ, Ramachandran R (2019) Dual regulation of lin28a by Myc is necessary during zebrafish retina regeneration. J Cell Biol 218(2):489–507
Popova EY, Imamura Kawasawa Y, Zhang SSM, Barnstable CJ (2021) Inhibition of epigenetic modifiers LSD1 and HDAC1 blocks rod photoreceptor death in mouse models of retinitis pigmentosa. J Neurosci 41(31):6775–6792
Mitra S, Sharma P, Kaur S, Khursheed MA, Gupta S, Ahuja R, Kurup AJ, Chaudhary M, Ramachandran R (2018) Histone deacetylase-mediated Muller glia reprogramming through Her4.1-Lin28a axis is essential for retina regeneration in zebrafish. iScience 7:68–84
Ye F, Chen Y, Hoang TN, Montgomery RL, Zhao XH, Bu H, Hu T, Taketo MM, van Es JH, Clevers H, Hsieh J, Bassel-Duby R, Olson EN, Lu QR (2009) HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the beta-catenin-TCF interaction. Nat Neurosci 12(7):829–838
Lebrun-Julien F, Suter U (2015) Combined HDAC1 and HDAC2 depletion promotes retinal ganglion cell survival after injury through reduction of p53 target gene expression. ASN Neuro 7(3)
Xue H, Liu J, Shi L, Yang H (2020) Overexpressed microRNA-539-5p inhibits inflammatory response of neurons to impede the progression of cerebral ischemic injury by histone deacetylase 1. Am J Physiol Cell Physiol 319(2):C381–C391
Marinova Z, Ren M, Wendland JR, Leng Y, Liang MH, Yasuda S, Leeds P, Chuang DM (2009) Valproic acid induces functional heat-shock protein 70 via class I histone deacetylase inhibition in cortical neurons: a potential role of Sp1 acetylation. J Neurochem 111(4):976–987
Du W, Wang N, Li F, Jia K, An J, Liu Y, Wang Y, Zhu L, Zhao S, Hao J (2019) STAT3 phosphorylation mediates high glucose-impaired cell autophagy in an HDAC1-dependent and -independent manner in Schwann cells of diabetic peripheral neuropathy. FASEB J 33(7):8008–8021
Pita-Thomas W, Mahar M, Joshi A, Gan D, Cavalli V (2019) HDAC5 promotes optic nerve regeneration by activating the mTOR pathway. Exp Neurol 317:271–283
Shi L, Tian Z, Fu Q, Li H, Zhang L, Tian L, Mi W (2020) miR-217-regulated MEF2D-HDAC5/ND6 signaling pathway participates in the oxidative stress and inflammatory response after cerebral ischemia. Brain Res 1739:146835
Cai X, Li J, Wang M, She M, Tang Y, Li J, Li H, Hui H (2017) GLP-1 Treatment improves diabetic retinopathy by alleviating autophagy through GLP-1R-ERK1/2-HDAC6 signaling pathway. Int J Med Sci 14(12):1203–1212
Finsterwald C, Carrard A, Martin JL (2013) Role of salt-inducible kinase 1 in the activation of MEF2-dependent transcription by BDNF. PLoS One 8(1):e54545
Nakagawa Y, Kuwahara K, Harada M, Takahashi N, Yasuno S, Adachi Y, Kawakami R, Nakanishi M, Tanimoto K, Usami S, Kinoshita H, Saito Y, Nakao K (2006) Class II HDACs mediate CaMK-dependent signaling to NRSF in ventricular myocytes. J Mol Cell Cardiol 41(6):1010–1022
Yu M, Zhang L, Sun S, Zhang Z (2021) Gliquidone improves retinal injury to relieve diabetic retinopathy via regulation of SIRT1/Notch1 pathway. BMC Ophthalmol 21(1):451
Zhang TH, Huang CM, Gao X, Wang JW, Hao LL, Ji Q (2018) Gastrodin inhibits high glucose-induced human retinal endothelial cell apoptosis by regulating the SIRT1/TLR4/NFkappaBp65 signaling pathway. Mol Med Rep 17(6):7774–7780
Tong P, Peng QH, Gu LM, Xie WW, Li WJ (2019) LncRNA-MEG3 alleviates high glucose induced inflammation and apoptosis of retina epithelial cells via regulating miR-34a/SIRT1 axis. Exp Mol Pathol 107:102–109
Zheng Z, Chen H, Li J, Li T, Zheng B, Zheng Y, Jin H, He Y, Gu Q, Xu X (2012) Sirtuin 1-mediated cellular metabolic memory of high glucose via the LKB1/AMPK/ROS pathway and therapeutic effects of metformin. Diabetes 61(1):217–228
Wu Y, Pang Y, Wei W, Shao A, Deng C, Li X, Chang H, Hu P, Liu X, Zhang X (2020) Resveratrol protects retinal ganglion cell axons through regulation of the SIRT1-JNK pathway. Exp Eye Res 200:108249
Zhang M, Jiang N, Chu Y, Postnikova O, Varghese R, Horvath A, Cheema AK, Golestaneh N (2020) Dysregulated metabolic pathways in age-related macular degeneration. Sci Rep 10(1):2464
Chou WW, Chen KC, Wang YS, Wang JY, Liang CL, Juo SHH (2013) The role of SIRT1/AKT/ERK pathway in ultraviolet B induced damage on human retinal pigment epithelial cells. Toxicol In Vitro 27(6):1728–1736
Dudakovic A, Camilleri ET, Lewallen EA, McGee-Lawrence ME, Riester SM, Kakar S, Montecino M, Stein GS, Ryoo HM, Dietz AB, Westendorf JJ, van Wijnen AJ (2015) Histone deacetylase inhibition destabilizes the multi-potent state of uncommitted adipose-derived mesenchymal stromal cells. J Cell Physiol 230(1):52–62
Zhao M, Tao Y, Peng GH (2020) The role of histone acetyltransferases and histone deacetylases in photoreceptor differentiation and degeneration. Int J Med Sci 17(10):1307–1314
Remez LA, Onishi A, Menuchin-Lasowski Y, Biran A, Blackshaw S, Wahlin KJ, Zack DJ, Ashery-Padan R (2017) Pax6 is essential for the generation of late-born retinal neurons and for inhibition of photoreceptor-fate during late stages of retinogenesis. Dev Biol 432(1):140–150
Saha A, Tiwari S, Dharmarajan S, Otteson DC, Belecky-Adams TL (2018) Class I histone deacetylases in retinal progenitors and differentiating ganglion cells. Gene Expr Patterns 30:37–48
Ferreira RC, Popova EY, James J, Briones MRS, Zhang SS, Barnstable CJ (2017) Histone deacetylase 1 is essential for rod photoreceptor differentiation by regulating acetylation at histone H3 lysine 9 and histone H4 lysine 12 in the mouse retina. J Biol Chem 292(6):2422–2440
Albadri S, Naso F, Thauvin M, Gauron C, Parolin C, Duroure K, Vougny J, Fiori J, Boga C, Vriz S, Calonghi N, del Bene F (2019) Redox signaling via lipid peroxidation regulates retinal progenitor cell differentiation. Dev Cell 50(1):73–89.e6
Zhao X, Shan Q, Xue HH (2022) TCF1 in T cell immunity: a broadened frontier. Nat Rev Immunol 22(3):147–157
Chen J, Zhao KN, Vitetta L (2019) Effects of intestinal microbial(-)elaborated butyrate on oncogenic signaling pathways. Nutrients 11(5)
Klimova L, Kozmik Z (2014) Stage-dependent requirement of neuroretinal Pax6 for lens and retina development. Development 141(6):1292–1302
Thomas T, Loveland KL, Voss AK (2007) The genes coding for the MYST family histone acetyltransferases, Tip60 and Mof, are expressed at high levels during sperm development. Gene Expression Patterns 7(6):657–665
Kim CH, Kim JW, Jang SM, An JH, Song KH, Choi KH (2012) Transcriptional activity of paired homeobox Pax6 is enhanced by histone acetyltransferase Tip60 during mouse retina development. Biochem Biophys Res Commun 424(3):427–432
Kim C-H, An MJ, Kim DH, Kim JW (2017) Histone deacetylase 1 (HDAC1) regulates retinal development through a PAX6-dependent pathway. Biochem Biophys Res Commun 482(4):735–741
Chen B, Cepko CL (2007) Requirement of histone deacetylase activity for the expression of critical photoreceptor genes. BMC Dev Biol 7:78
Kim J-W, Jang SM, Kim CH, An JH, Choi KH (2012) Transcriptional activity of neural retina leucine zipper (Nrl) is regulated by c-Jun N-terminal kinase and Tip60 during retina development. Mol Cell Biol 32(9):1720–1732
Peng GH, Chen S (2007) Crx activates opsin transcription by recruiting HAT-containing co-activators and promoting histone acetylation. Hum Mol Genet 16(20):2433–2452
Solovei I, Kreysing M, Lanctôt C, Kösem S, Peichl L, Cremer T, Guck J, Joffe B (2009) Nuclear architecture of rod photoreceptor cells adapts to vision in mammalian evolution. Cell 137(2):356–368
Hennig AK, Peng GH, Chen S (2013) Transcription coactivators p300 and CBP are necessary for photoreceptor-specific chromatin organization and gene expression. PLoS One 8(7):e69721
Voyvodic JT, Burne JF, Raff MC (1995) Quantification of normal cell death in the rat retina: implications for clone composition in cell lineage analysis. Eur J Neurosci 7(12):2469–2478
Chen B, Cepko CL (2009) HDAC4 regulates neuronal survival in normal and diseased retinas. Science 323(5911):256–259
Gaub P, Joshi Y, Wuttke A, Naumann U, Schnichels S, Heiduschka P, di Giovanni S (2011) The histone acetyltransferase p300 promotes intrinsic axonal regeneration. Brain 134(7):2134–2148
Schwechter B, Millet LE, Levin LA (2007) Histone deacetylase inhibition-mediated differentiation of RGC-5 cells and interaction with survival. Invest Ophthalmol Vis Sci 48(6):2845–2857
Biermann J, Boyle J, Pielen A, Lagrèze WA (2011) Histone deacetylase inhibitors sodium butyrate and valproic acid delay spontaneous cell death in purified rat retinal ganglion cells. Mol Vis 17:395–403
Narita T, Weinert BT, Choudhary C (2019) Functions and mechanisms of non-histone protein acetylation. Nat Rev Mol Cell Biol 20(3):156–174
Choi HK, Choi Y, Kang HB, Lim EJ, Park SY, Lee HS, Park JM, Moon J, Kim YJ, Choi I, Joe EH, Choi KC, Yoon HG (2015) PINK1 positively regulates HDAC3 to suppress dopaminergic neuronal cell death. Hum Mol Genet 24(4):1127–1141
Demyanenko S, Sharifulina S (2021) The role of post-translational acetylation and deacetylation of signaling proteins and transcription factors after cerebral ischemia: facts and hypotheses. Int J Mol Sci 22(15)
Bringmann A, Pannicke T, Biedermann B, Francke M, Iandiev I, Grosche J, Wiedemann P, Albrecht J, Reichenbach A (2009) Role of retinal glial cells in neurotransmitter uptake and metabolism. Neurochem Int 54(3-4):143–160
Bringmann A, Wiedemann P (2012) Muller glial cells in retinal disease. Ophthalmologica 227(1):1–19
Yang Q, Zhou Y, Sun Y, Luo Y, Shen Y, Shao A (2020) Will sirtuins be promising therapeutic targets for TBI and associated neurodegenerative diseases? Front Neurosci 14:791
Wei W, Hu P, Qin M, Chen G, Wang F, Yao S, Jin M, Xie Z, Zhang X (2022) SIRT4 is highly expressed in retinal Muller glial cells. Front Neurosci 16:840443
Jorstad N, Wilken MS, Grimes WN, Wohl SG, VandenBosch LS, Yoshimatsu T, Wong RO, Rieke F, Reh TA (2017) Stimulation of functional neuronal regeneration from Müller glia in adult mice. Nature 548(7665):103–107
Johnson J, Tian N, Caywood MS, Reimer RJ, Edwards RH, Copenhagen DR (2003) Vesicular neurotransmitter transporter expression in developing postnatal rodent retina: GABA and glycine precede glutamate. J Neurosci 23(2):518–529
Ramírez M, Hernández-Montoya J, Sánchez-Serrano SL, Ordaz B, Ferraro S, Quintero H, Peña-Ortega F, Lamas M (2012) GABA-mediated induction of early neuronal markers expression in postnatal rat progenitor cells in culture. Neuroscience 224:210–222
Hatakeyama D, Sunada H, Totani Y, Watanabe T, Felletár I, Fitchett A, Eravci M, Anagnostopoulou A, Miki R, Okada A, Abe N, Kuzuhara T, Kemenes I, Ito E, Kemenes G (2022) Molecular and functional characterization of an evolutionarily conserved CREB-binding protein in the Lymnaea CNS. FASEB J 36(11):e22593
Campa C, Costagliola C, Incorvaia C, Sheridan C, Semeraro F, de Nadai K, Sebastiani A, Parmeggiani F (2010) Inflammatory mediators and angiogenic factors in choroidal neovascularization: pathogenetic interactions and therapeutic implications. Mediators Inflamm 2010:1–14
Ishida T, Yoshida T, Shinohara K, Cao K, Nakahama KI, Morita I, Ohno-Matsui K (2017) Potential role of sirtuin 1 in Muller glial cells in mice choroidal neovascularization. PLoS One 12(9):e0183775
Zia A, Sahebdel F, Farkhondeh T, Ashrafizadeh M, Zarrabi A, Hushmandi K, Samarghandian S (2021) A review study on the modulation of SIRT1 expression by miRNAs in aging and age-associated diseases. Int J Biol Macromol 188:52–61
Mimura T, Kaji Y, Noma H, Funatsu H, Okamoto S (2013) The role of SIRT1 in ocular aging. Exp Eye Res 116:17–26
Warfvinge K, Kamme C, Englund U, Wictorin K (2001) Retinal integration of grafts of brain-derived precursor cell lines implanted subretinally into adult, normal rats. Exp Neurol 169(1):1–12
Peng CH, Chang YL, Kao CL, Tseng LM, Wu CC, Chen YC, Tsai CY, Woung LC, Liu JH, Chiou SH, Chen SJ (2010) SirT1—a sensor for monitoring self-renewal and aging process in retinal stem cells. Sensors (Basel) 10(6):6172–6194
Ozawa Y, Kubota S, Narimatsu T, Yuki K, Koto T, Sasaki M, Tsubota K (2010) Retinal aging and sirtuins. Ophthalmic Res 44(3):199–203
Satoh A, Stein L, Imai S (2011) The role of mammalian sirtuins in the regulation of metabolism, aging, and longevity. Handb Exp Pharmacol 206:125–162
Ban N, Ozawa Y, Inaba T, Miyake S, Watanabe M, Shinmura K, Tsubota K (2013) Light-dark condition regulates sirtuin mRNA levels in the retina. Exp Gerontol 48(11):1212–1217
Zhong L, D'Urso A, Toiber D, Sebastian C, Henry RE, Vadysirisack DD, Guimaraes A, Marinelli B, Wikstrom JD, Nir T, Clish CB, Vaitheesvaran B, Iliopoulos O, Kurland I, Dor Y, Weissleder R, Shirihai OS, Ellisen LW, Espinosa JM, Mostoslavsky R (2010) The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha. Cell 140(2):280–293
Silberman DM, Ross K, Sande PH, Kubota S, Ramaswamy S, Apte RS, Mostoslavsky R (2014) SIRT6 is required for normal retinal function. PLoS One 9(6):e98831
Feng Y, Liang J, Zhai Y, Sun J, Wang J, She X, Gu Q, Liu Y, Zhu H, Luo X, Sun X (2018) Autophagy activated by SIRT6 regulates Abeta induced inflammatory response in RPEs. Biochem Biophys Res Commun 496(4):1148–1154
Leus NG, Zwinderman MR, Dekker FJ (2016) Histone deacetylase 3 (HDAC 3) as emerging drug target in NF-kappaB-mediated inflammation. Curr Opin Chem Biol 33:160–168
Li P, Ge J, Li H (2020) Lysine acetyltransferases and lysine deacetylases as targets for cardiovascular disease. Nat Rev Cardiol 17(2):96–115
Nishino TG, Miyazaki M, Hoshino H, Miwa Y, Horinouchi S, Yoshida M (2008) 14-3-3 regulates the nuclear import of class IIa histone deacetylases. Biochem Biophys Res Commun 377(3):852–856
Iaconelli J, Lalonde J, Watmuff B, Liu B, Mazitschek R, Haggarty SJ, Karmacharya R (2017) Lysine deacetylation by HDAC6 regulates the kinase activity of AKT in human neural progenitor cells. ACS Chem Biol 12(8):2139–2148
Corso-Díaz X, Jaeger C, Chaitankar V, Swaroop A (2018) Epigenetic control of gene regulation during development and disease: a view from the retina. Prog Retin Eye Res 65:1–27
Sancho-Pelluz J, Alavi MV, Sahaboglu A, Kustermann S, Farinelli P, Azadi S, van Veen T, Romero FJ, Paquet-Durand F, Ekström P (2010) Excessive HDAC activation is critical for neurodegeneration in the rd1 mouse. Cell Death Dis 1:e24
Botto C, Rucli M, Tekinsoy MD, Pulman J, Sahel JA, Dalkara D (2022) Early and late stage gene therapy interventions for inherited retinal degenerations. Prog Retin Eye Res 86:100975
Zhang Q (2016) Retinitis pigmentosa: progress and perspective. Asia Pac J Ophthalmol (Phila) 5(4):265–271
Brunet AA, Harvey AR, Carvalho LS (2022) Primary and secondary cone cell death mechanisms in inherited retinal diseases and potential treatment options. Int J Mol Sci 23(2)
Trifunović D, Petridou E, Comitato A, Marigo V, Ueffing M, Paquet-Durand F (2018) Primary rod and cone degeneration is prevented by HDAC inhibition. Adv Exp Med Biol 1074:367–373
Samardzija M, Corna A, Gomez-Sintes R, Jarboui MA, Armento A, Roger JE, Petridou E, Haq W, Paquet-Durand F, Zrenner E, de la Villa P, Zeck G, Grimm C, Boya P, Ueffing M, Trifunović D (2021) HDAC inhibition ameliorates cone survival in retinitis pigmentosa mice. Cell Death Differ 28(4):1317–1332
Trifunović D, Arango-Gonzalez B, Comitato A, Barth M, del Amo E, Kulkarni M, Sahaboglu A, Hauck SM, Urtti A, Arsenijevic Y, Ueffing M, Marigo V, Paquet-Durand F (2016) HDAC inhibition in the cpfl1 mouse protects degenerating cone photoreceptors in vivo. Hum Mol Genet 25(20):4462–4472
Koriyama Y, Sugitani K, Ogai K, Kato S (2014) Heat shock protein 70 induction by valproic acid delays photoreceptor cell death by N-methyl-N-nitrosourea in mice. J Neurochem 130(5):707–719
Yoshida T, Ozawa Y, Suzuki K, Yuki K, Ohyama M, Akamatsu W, Matsuzaki Y, Shimmura S, Mitani K, Tsubota K, Okano H (2014) The use of induced pluripotent stem cells to reveal pathogenic gene mutations and explore treatments for retinitis pigmentosa. Mol Brain 7:45
Ozawa Y, Toda E, Homma K, Osada H, Nagai N, Tsubota K, Okano H (2022) Effects of epigenetic modification of PGC-1alpha by a chemical chaperon on mitochondria biogenesis and visual function in retinitis pigmentosa. Cells 11(9)
Sundaramurthi H, Roche SL, Grice GL, Moran A, Dillion ET, Campiani G, Nathan JA, Kennedy BN (2020) Selective histone deacetylase 6 inhibitors restore cone photoreceptor vision or outer segment morphology in zebrafish and mouse models of retinal blindness. Front Cell Dev Biol 8:689
Shi K, Zhu X, Wu J, Chen Y, Zhang J, Sun X (2021) Centromere protein E as a novel biomarker and potential therapeutic target for retinoblastoma. Bioengineered 12(1):5950–5970
Rao RC, Dou Y (2015) Hijacked in cancer: the KMT2 (MLL) family of methyltransferases. Nat Rev Cancer 15(6):334–346
Duan S, Gong X, Liu X, Cui W, Chen K, Mao L, Jun S, Zhou R, Sang Y, Huang G (2019) Histone deacetylase inhibitor, AR-42, exerts antitumor effects by inducing apoptosis and cell cycle arrest in Y79 cells. J Cell Physiol 234(12):22411–22423
Liu M, Yao B, Gui T, Guo C, Wu X, Li J, Ma L, Deng Y, Xu P, Wang Y, Yang D, Li Q, Zeng X, Li X, Hu R, Ge J, Yu Z, Chen Y, Chen B et al (2020) PRMT5-dependent transcriptional repression of c-Myc target genes promotes gastric cancer progression. Theranostics 10(10):4437–4452
Okuyama H, Endo H, Akashika T, Kato K, Inoue M (2010) Downregulation of c-MYC protein levels contributes to cancer cell survival under dual deficiency of oxygen and glucose. Cancer Res 70(24):10213–10223
Wang C, Tai Y, Lisanti MP, Liao DJ (2011) c-Myc induction of programmed cell death may contribute to carcinogenesis: a perspective inspired by several concepts of chemical carcinogenesis. Cancer Biol Ther 11(7):615–626
Yu N, Chen P, Wang Q, Liang M, Qiu J, Zhou P, Yang M, Yang P, Wu Y, Han X, Ge J, Zhuang J, Yu K (2020) Histone deacetylase inhibitors differentially regulate c-Myc expression in retinoblastoma cells. Oncol Lett 19(1):460–468
Sanford JD, Yang J, Han J, Tollini LA, Jin A, Zhang Y (2021) MDMX is essential for the regulation of p53 protein levels in the absence of a functional MDM2 C-terminal tail. BMC Mol Cell Biol 22(1):46
Kawano T, Akiyama M, Agawa-Ohta M, Mikami-Terao Y, Iwase S, Yanagisawa T, Ida H, Agata N, Yamada H (2010) Histone deacetylase inhibitors valproic acid and depsipeptide sensitize retinoblastoma cells to radiotherapy by increasing H2AX phosphorylation and p53 acetylation-phosphorylation. Int J Oncol 37(4):787–795
Zhang Y, Wu D, Xia F, Xian H, Zhu X, Cui H, Huang Z (2016) Downregulation of HDAC9 inhibits cell proliferation and tumor formation by inducing cell cycle arrest in retinoblastoma. Biochem Biophys Res Commun 473(2):600–606
Jin Q, He W, Chen L, Yang Y, Shi K, You Z (2018) MicroRNA-101-3p inhibits proliferation in retinoblastoma cells by targeting EZH2 and HDAC9. Exp Ther Med 16(3):1663–1670
Xu L, Li W, Shi Q, Wang M, Li H, Yang X, Zhang J (2020) MicroRNA936 inhibits the malignant phenotype of retinoblastoma by directly targeting HDAC9 and deactivating the PI3K/AKT pathway. Oncol Rep 43(2):635–645
Zhu Y, Hao F (2021) Knockdown of long noncoding RNA HCP5 suppresses the malignant behavior of retinoblastoma by sponging miR36195p to target HDAC9. Int J Mol Med 47(5)
Thomas CJ, Mirza RG, Gill MK (2021) Age-related macular degeneration. Med Clin North Am 105(3):473–491
Nashine S (2021) Potential therapeutic candidates for age-related macular degeneration (AMD). Cells 10(9)
Pennington KL, DeAngelis MM (2015) Epigenetic mechanisms of the aging human retina. J Exp Neurosci 9(Suppl 2):51–79
Peng CH, Cherng JY, Chiou GY, Chen YC, Chien CH, Kao CL, Chang YL, Chien Y, Chen LK, Liu JH, Chen SJ, Chiou SH (2011) Delivery of Oct4 and SirT1 with cationic polyurethanes-short branch PEI to aged retinal pigment epithelium. Biomaterials 32(34):9077–9088
Sharma R, Bose D, Maminishkis A, Bharti K (2020) Retinal pigment epithelium replacement therapy for age-related macular degeneration: are we there yet? Annu Rev Pharmacol Toxicol 60:553–572
Yoshida K, Moein A, Bittner T, Ostrowitzki S, Lin H, Honigberg L, Jin JY, Quartino A (2020) Pharmacokinetics and pharmacodynamic effect of crenezumab on plasma and cerebrospinal fluid beta-amyloid in patients with mild-to-moderate Alzheimer’s disease. Alzheimers Res Ther 12(1):16
Wang S, Tang YJ (2021) Sulforaphane ameliorates amyloid-beta-induced inflammatory injury by suppressing the PARP1/SIRT1 pathway in retinal pigment epithelial cells. Bioengineered 12(1):7079–7089
Hamid MA, Moustafa MT, Nashine S, Costa RD, Schneider K, Atilano SR, Kuppermann BD, Kenney MC (2021) Anti-VEGF drugs influence epigenetic regulation and AMD-specific molecular markers in ARPE-19 cells. Cells 10(4)
Nashine S, Nesburn AB, Kuppermann BD, Kenney MC (2019) Age-related macular degeneration (AMD) mitochondria modulate epigenetic mechanisms in retinal pigment epithelial cells. Exp Eye Res 189:107701
Hsu TJ, Nepali K, Tsai CH, Imtiyaz Z, Lin FL, Hsiao G, Lai MJ, Cheng YW (2021) The HDAC/HSP90 inhibitor G570 attenuated blue light-induced cell migration in RPE cells and neovascularization in mice through decreased VEGF production. Molecules 26(14)
Luu J, Kallestad L, Hoang T, Lewandowski D, Dong Z, Blackshaw S, Palczewski K (2020) Epigenetic hallmarks of age-related macular degeneration are recapitulated in a photosensitive mouse model. Hum Mol Genet 29(15):2611–2624
Pan J, Zhao L (2021) Long non-coding RNA histone deacetylase 4 antisense RNA 1 (HDAC4-AS1) inhibits HDAC4 expression in human ARPE-19 cells with hypoxic stress. Bioengineered 12(1):2228–2237
Wilkinson CP, Ferris FL III, Klein RE, Lee PP, Agardh CD, Davis M, Dills D, Kampik A, Pararajasegaram R, Verdaguer JT (2003) Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology 110(9):1677–1682
Kowluru RA, Kowluru A, Mishra M, Kumar B (2015) Oxidative stress and epigenetic modifications in the pathogenesis of diabetic retinopathy. Prog Retin Eye Res 48:40–61
Kowluru RA, Mishra M (2015) Contribution of epigenetics in diabetic retinopathy. Sci China Life Sci 58(6):556–563
Zhong Q, Kowluru RA (2010) Role of histone acetylation in the development of diabetic retinopathy and the metabolic memory phenomenon. J Cell Biochem 110(6):1306–1313
Taurone S, de Ponte C, Rotili D, de Santis E, Mai A, Fiorentino F, Scarpa S, Artico M, Micera A (2022) Biochemical functions and clinical characterizations of the sirtuins in diabetes-induced retinal pathologies. Int J Mol Sci 23(7)
Zorrilla-Zubilete MA, Yeste A, Quintana FJ, Toiber D, Mostoslavsky R, Silberman DM (2018) Epigenetic control of early neurodegenerative events in diabetic retinopathy by the histone deacetylase SIRT6. J Neurochem 144(2):128–138
Yang JJ, Tao H, Liu LP, Hu W, Deng ZY, Li J (2017) miR-200a controls hepatic stellate cell activation and fibrosis via SIRT1/Notch1 signal pathway. Inflamm Res 66(4):341–352
Tu Y, Zhu M, Wang Z, Wang K, Chen L, Liu W, Shi Q, Zhao Q, Sun Y, Wang X, Song E, Liu X (2020) Melatonin inhibits Muller cell activation and pro-inflammatory cytokine production via upregulating the MEG3/miR-204/Sirt1 axis in experimental diabetic retinopathy. J Cell Physiol 235(11):8724–8735
Tu Y, Song E, Wang Z, Ji N, Zhu L, Wang K, Sun H, Zhang Y, Zhu Q, Liu X, Zhu M (2021) Melatonin attenuates oxidative stress and inflammation of Muller cells in diabetic retinopathy via activating the Sirt1 pathway. Biomed Pharmacother 137:111274
Picconi F, Parravano M, Sciarretta F, Fulci C, Nali M, Frontoni S, Varano M, Caccuri AM (2019) Activation of retinal Muller cells in response to glucose variability. Endocrine 65(3):542–549
Kadiyala CS, Zheng L, Du Y, Yohannes E, Kao HY, Miyagi M, Kern TS (2012) Acetylation of retinal histones in diabetes increases inflammatory proteins: effects of minocycline and manipulation of histone acetyltransferase (HAT) and histone deacetylase (HDAC). J Biol Chem 287(31):25869–25880
Chen E, Looman M, Laouri M, Gallagher M, van Nuys K, Lakdawalla D, Fortuny J (2010) Burden of illness of diabetic macular edema: literature review. Curr Med Res Opin 26(7):1587–1597
Desjardins D, Liu Y, Crosson CE, Ablonczy Z (2016) Histone deacetylase inhibition restores retinal pigment epithelium function in hyperglycemia. PLoS One 11(9):e0162596
Abouhish H, Thounaojam MC, Jadeja RN, Gutsaeva DR, Powell FL, Khriza M, Martin PM, Bartoli M (2020) Inhibition of HDAC6 attenuates diabetes-induced retinal redox imbalance and microangiopathy. Antioxidants (Basel) 9(7)
Che S, Wu S, Yu P (2022) Downregulated HDAC3 or up-regulated microRNA-296-5p alleviates diabetic retinopathy in a mouse model. Regen Ther 21:1–8
Wang W, Wang Q, Wan D, Sun Y, Wang L, Chen H, Liu C, Petersen RB, Li J, Xue W, Zheng L, Huang K (2017) Histone HIST1H1C/H1.2 regulates autophagy in the development of diabetic retinopathy. Autophagy 13(5):941–954
Daniel S, Meyer KJ, Clark AF, Anderson MG, McDowell CM (2019) Effect of ocular hypertension on the pattern of retinal ganglion cell subtype loss in a mouse model of early-onset glaucoma. Exp Eye Res 185:107703
Pelzel HR, Schlamp CL, Waclawski M, Shaw MK, Nickells RW (2012) Silencing of Fem1cR3 gene expression in the DBA/2J mouse precedes retinal ganglion cell death and is associated with histone deacetylase activity. Invest Ophthalmol Vis Sci 53(3):1428–1435
Kimura A, Guo X, Noro T, Harada C, Tanaka K, Namekata K, Harada T (2015) Valproic acid prevents retinal degeneration in a murine model of normal tension glaucoma. Neurosci Lett 588:108–113
Sharma A, Anumanthan G, Reyes M, Chen H, Brubaker JW, Siddiqui S, Gupta S, Rieger FG, Mohan RR (2016) Epigenetic modification prevents excessive wound healing and scar formation after glaucoma filtration surgery. Invest Ophthalmol Vis Sci 57(7):3381–3389
Guo X, Kimura A, Azuchi Y, Akiyama G, Noro T, Harada C, Namekata K, Harada T (2016) Caloric restriction promotes cell survival in a mouse model of normal tension glaucoma. Sci Rep 6:33950
Schmitt HM, Grosser JA, Schlamp CL, Nickells RW (2020) Targeting HDAC3 in the DBA/2J spontaneous mouse model of glaucoma. Exp Eye Res 200:108244
Siwak M, Maślankiewicz M, Nowak-Zduńczyk A, Rozpędek W, Wojtczak R, Szymanek K, Szaflik M, Szaflik J, Szaflik JP, Majsterek I (2018) The relationship between HDAC6, CXCR3, and SIRT1 genes expression levels with progression of primary open-angle glaucoma. Ophthalmic Genet 39(3):325–331
Yang Y, Abdulatef ALSWA, Zhang LS, Jiang H, Zeng Z, Li H, Xia X (2020) Cross-talk between MYOC p. Y437H mutation and TGF-beta2 in the pathology of glaucoma. Int J Med Sci 17(8):1062–1070
Fujimoto T, Inoue-Mochita M, Iraha S, Tanihara H, Inoue T (2021) Suberoylanilide hydroxamic acid (SAHA) inhibits transforming growth factor-beta 2-induced increases in aqueous humor outflow resistance. J Biol Chem 297(3):101070
Zaidi SAH, Guzman W, Singh S, Mehrotra S, Husain S (2020) Changes in class I and IIb HDACs by delta-opioid in chronic rat glaucoma model. Invest Ophthalmol Vis Sci 61(14):4
Bermudez JY, Webber HC, Patel GC, Liu X, Cheng YQ, Clark AF, Mao W (2016) HDAC inhibitor-mediated epigenetic regulation of glaucoma-associated TGFbeta2 in the trabecular meshwork. Invest Ophthalmol Vis Sci 57(8):3698–3707
Fuchshofer R, Tamm ER (2012) The role of TGF-beta in the pathogenesis of primary open-angle glaucoma. Cell Tissue Res 347(1):279–290
Danford ID, Verkuil LD, Choi DJ, Collins DW, Gudiseva HV, Uyhazi KE, Lau MK, Kanu LN, Grant GR, Chavali VRM, O'Brien JM (2017) Characterizing the “POAGome”: a bioinformatics-driven approach to primary open-angle glaucoma. Prog Retin Eye Res 58:89–114
Zhang YE (2009) Non-Smad pathways in TGF-beta signaling. Cell Res 19(1):128–139
Dai C, Webster KA, Bhatt A, Tian H, Su G, Li W (2021) Concurrent physiological and pathological angiogenesis in retinopathy of prematurity and emerging therapies. Int J Mol Sci 22(9)
Iizuka N, Morita A, Kawano C, Mori A, Sakamoto K, Kuroyama M, Ishii K, Nakahara T (2018) Anti-angiogenic effects of valproic acid in a mouse model of oxygen-induced retinopathy. J Pharmacol Sci 138(3):203–208
Bonanni D, Citarella A, Moi D, Pinzi L, Bergamini E, Rastelli G (2022) Dual targeting strategies on histone deacetylase 6 (HDAC6) and heat shock protein 90 (Hsp90). Curr Med Chem 29(9):1474–1502
Wang X, Wang L, Sun Y, Chen B, Xiong L, Chen J, Huang M, Wu J, Tan X, Zheng Y, Huang S, Liu Y (2020) MiR-22-3p inhibits fibrotic cataract through inactivation of HDAC6 and increase of alpha-tubulin acetylation. Cell Prolif 53(11):e12911
Ran J, Liu M, Feng J, Li H, Ma H, Song T, Cao Y, Zhou P, Wu Y, Yang Y, Yang Y, Yu F, Guo H, Zhang L, Xie S, Li D, Gao J, Zhang X, Zhu X, Zhou J (2020) ASK1-mediated phosphorylation blocks HDAC6 ubiquitination and degradation to drive the disassembly of photoreceptor connecting cilia. Dev Cell 53(3):287–299.e5
Ran J, Zhang Y, Zhang S, Li H, Zhang L, Li Q, Qin J, Li D, Sun L, Xie S, Zhang X, Liu L, Liu M, Zhou J (2022) Targeting the HDAC6-cilium axis ameliorates the pathological changes associated with retinopathy of prematurity. Adv Sci (Weinh) 9(21):e2105365
Deng B, Luo Q, Halim A, Liu Q, Zhang B, Song G (2020) The antiangiogenesis role of histone deacetylase inhibitors: their potential application to tumor therapy and tissue repair. DNA Cell Biol 39(2):167–176
Zhao K, Jiang Y, Zhang J, Shi J, Zheng P, Yang C, Chen Y (2022) Celastrol inhibits pathologic neovascularization in oxygen-induced retinopathy by targeting the miR-17-5p/HIF-1alpha/VEGF pathway. Cell Cycle 21(19):2091–2108
Schmitt HM, Schlamp CL, Nickells RW (2016) Role of HDACs in optic nerve damage-induced nuclear atrophy of retinal ganglion cells. Neurosci Lett 625:11–15
Biermann J, Grieshaber P, Goebel U, Martin G, Thanos S, Giovanni SD, Lagrèze WA (2010) Valproic acid-mediated neuroprotection and regeneration in injured retinal ganglion cells. Invest Ophthalmol Vis Sci 51(1):526–534
Pelzel HR, Schlamp CL, Nickells RW (2010) Histone H4 deacetylation plays a critical role in early gene silencing during neuronal apoptosis. BMC Neurosci 11:62
Zhang ZZ, Gong YY, Shi YH, Zhang W, Qin XH, Wu XW (2012) Valproate promotes survival of retinal ganglion cells in a rat model of optic nerve crush. Neuroscience 224:282–293
Schmitt HM, Pelzel HR, Schlamp CL, Nickells RW (2014) Histone deacetylase 3 (HDAC3) plays an important role in retinal ganglion cell death after acute optic nerve injury. Mol Neurodegener 9:39
Schmitt HM, Schlamp CL, Nickells RW (2018) Targeting HDAC3 activity with RGFP966 protects against retinal ganglion cell nuclear atrophy and apoptosis after optic nerve injury. J Ocul Pharmacol Ther 34(3):260–273
Sung MS, Moon MJ, Thomas RG, Kim SY, Lee JS, Jeong YY, Park IK, Park SW (2020) Intravitreal injection of liposomes loaded with a histone deacetylase inhibitor promotes retinal ganglion cell survival in a mouse model of optic nerve crush. Int J Mol Sci 21(23)
Alsarraf O, Fan J, Dahrouj M, Chou CJ, Menick DR, Crosson CE (2014) Acetylation: a lysine modification with neuroprotective effects in ischemic retinal degeneration. Exp Eye Res 127:124–131
Fan J, Alsarraf O, Chou CJ, Yates PW, Goodwin NC, Rice DS, Crosson CE (2016) Ischemic preconditioning, retinal neuroprotection and histone deacetylase activities. Exp Eye Res 146:269–275
Sung MS, Heo H, Eom GH, Kim SY, Piao H, Guo Y, Park SW (2019) HDAC2 regulates glial cell activation in ischemic mouse retina. Int J Mol Sci 20(20)
Crosson CE, Mani SK, Husain S, Alsarraf O, Menick DR (2010) Inhibition of histone deacetylase protects the retina from ischemic injury. Invest Ophthalmol Vis Sci 51(7):3639–3645
Zhang Z, Tong NT, Gong YY, Qiu QH, Yin LL, Lv XH, Wu XW (2011) Valproate protects the retina from endoplasmic reticulum stress-induced apoptosis after ischemia-reperfusion injury. Neurosci Lett 504(2):88–92
Fan J, Alsarraf O, Dahrouj M, Platt KA, Chou CJ, Rice DS, Crosson CE (2013) Inhibition of HDAC2 protects the retina from ischemic injury. Invest Ophthalmol Vis Sci 54(6):4072–4080
Mishra M, Zhong Q, Kowluru RA (2014) Epigenetic modifications of Nrf2-mediated glutamate-cysteine ligase: implications for the development of diabetic retinopathy and the metabolic memory phenomenon associated with its continued progression. Free Radic Biol Med 75:129–139
Yuan H, Li H, Yu P, Fan Q, Zhang X, Huang W, Shen J, Cui Y, Zhou W (2018) Involvement of HDAC6 in ischaemia and reperfusion-induced rat retinal injury. BMC Ophthalmol 18(1):300
Burke TL, Miller JL, Grant PA (2013) Direct inhibition of Gcn5 protein catalytic activity by polyglutamine-expanded ataxin-7. J Biol Chem 288(47):34266–34275
Palhan VB, Chen S, Peng GH, Tjernberg A, Gamper AM, Fan Y, Chait BT, la Spada AR, Roeder RG (2005) Polyglutamine-expanded ataxin-7 inhibits STAGA histone acetyltransferase activity to produce retinal degeneration. Proc Natl Acad Sci U S A 102(24):8472–8477
Helmlinger D, Hardy S, Sasorith S, Klein F, Robert F, Weber C, Miguet L, Potier N, van-Dorsselaer A, Wurtz JM, Mandel JL, Tora L, Devys D (2004) Ataxin-7 is a subunit of GCN5 histone acetyltransferase-containing complexes. Hum Mol Genet 13(12):1257–1265
Helmlinger D, Hardy S, Abou-Sleymane G, Eberlin A, Bowman AB, Gansmüller A, Picaud S, Zoghbi HY, Trottier Y, Tora L, Devys D (2006) Glutamine-expanded ataxin-7 alters TFTC/STAGA recruitment and chromatin structure leading to photoreceptor dysfunction. PLoS Biol 4(3):e67
Chen YC, Gatchel JR, Lewis RW, Mao CA, Grant PA, Zoghbi HY, Dent SYR (2012) Gcn5 loss-of-function accelerates cerebellar and retinal degeneration in a SCA7 mouse model. Hum Mol Genet 21(2):394–405
Kizilyaprak C, Spehner D, Devys D, Schultz P (2011) The linker histone H1C contributes to the SCA7 nuclear phenotype. Nucleus 2(5):444–454
Kaczmarek JV, Bogan CM, Pierce JM, Tao YK, Chen SC, Liu Q, Liu X, Boyd KL, Calcutt MW, Bridges TM, Lindsley CW, Friedman DL, Richmond A, Daniels AB (2021) Intravitreal HDAC inhibitor belinostat effectively eradicates vitreous seeds without retinal toxicity in vivo in a rabbit retinoblastoma model. Invest Ophthalmol Vis Sci 62(14):8
Acknowledgements
We thank members of Yao laboratory for their kind suggestion and technical assistance.
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This work was supported by the National Natural Science Foundation of China (No. 31970930), Hubei Natural Science Foundation (No. 2020CFA069, No. 2018CFB434), and Neuroscience Team Development Project of Wuhan University of Science and Technology (No. 1180002).
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JW and SF: conceptualization, design, writing—original draft, visualization; QZ, HQ, and CX: data curation and review and editing; XF, LY, and YZ: literature search and collection; KY: writing—review and editing, supervision, and funding resources.
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Wang, J., Feng, S., Zhang, Q. et al. Roles of Histone Acetyltransferases and Deacetylases in the Retinal Development and Diseases. Mol Neurobiol 60, 2330–2354 (2023). https://doi.org/10.1007/s12035-023-03213-1
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DOI: https://doi.org/10.1007/s12035-023-03213-1