# Epigenetic Switches in Retinal Homeostasis and Target for Drug Development **Authors:** Kalpana Rajanala, Arun Upadhyay PMC · DOI: 10.3390/ijms25052840 · International Journal of Molecular Sciences · 2024-02-29 ## TL;DR This paper reviews how epigenetic changes help maintain retinal health and could be used to develop new treatments for retinal diseases. ## Contribution The paper compiles current knowledge on epigenetic regulation in retinal homeostasis and identifies potential therapeutic targets. ## Key findings - Epigenetic switches like DNA methylation and non-coding RNAs regulate retinal gene expression. - These epigenetic mechanisms are crucial for retinal development and response to injury. - Understanding these switches could lead to new drug targets for retinal diseases. ## Abstract Retinal homeostasis, a tightly regulated process maintaining the functional integrity of the retina, is vital for visual function. Emerging research has unveiled the critical role of epigenetic regulation in controlling gene expression patterns during retinal development, maintenance, and response to mutational loads and injuries. Epigenetic switches, including DNA methylation, histone modifications, and non-coding RNAs, play pivotal roles in orchestrating retinal gene expression and cellular responses through various intracellular, extracellular, and environmental modulators. This review compiles the current knowledge on epigenetic switches in retinal homeostasis, providing a deeper understanding of their impact on retinal structural integrity and function and using them as potential targets for therapeutic interventions. ## Full-text entities - **Genes:** MIR9-3 (microRNA 9-3) [NCBI Gene 407051] {aka MIRN9-3, hsa-mir-9-3, miRNA9-3, mir-9-3}, Cfh (complement component factor h) [NCBI Gene 12628] {aka Mud-1, NOM, Sas-1, Sas1}, MIR106A (microRNA 106a) [NCBI Gene 406899] {aka MIRN106A, mir-106, mir-106a}, H2AC18 (H2A clustered histone 18) [NCBI Gene 8337] {aka H2A, H2A.2, H2A/O, H2A/q, H2AFO, H2a-615}, Meis2 (Meis homeobox 2) [NCBI Gene 17536] {aka A430109D20Rik, Mrg1, Stra10}, MIR96 (microRNA 96) [NCBI Gene 407053] {aka DFNA50, MIRN96, hsa-mir-96, miR-96, miRNA96}, Nr2e3 (nuclear receptor subfamily 2, group E, member 3) [NCBI Gene 23958] {aka A930035N01Rik, PNR, RNR, rd7}, Hdac1 (histone deacetylase 1) [NCBI Gene 433759] {aka HD1, Hdac1-ps, MommeD5, RPD3}, Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, Vax2os (ventral anterior homeobox 2, opposite strand) [NCBI Gene 574519] {aka Vas2os, Vax2os1, Vax2os2}, MIR204 (microRNA 204) [NCBI Gene 406987] {aka MIRN204, RDICC, miRNA204, mir-204}, Pten (phosphatase and tensin homolog) [NCBI Gene 19211] {aka 2310035O07Rik, A130070J02Rik, B430203M17Rik, MMAC1, PTENbeta, TEP1}, Nodal (nodal growth differentiation factor) [NCBI Gene 18119] {aka Tg.413d}, Ezh2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) [NCBI Gene 14056] {aka Enx-1, Enx1h, KMT6, mKIAA4065}, SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4) [NCBI Gene 395932] {aka BRG, BRG1}, KAT8 (lysine acetyltransferase 8) [NCBI Gene 84148] {aka LIGOWS, MOF, MYST1, ZC2HC8, hMOF}, Hdac6 (histone deacetylase 6) [NCBI Gene 15185] {aka Hd6, Hdac5, Sfc6, mHDA2}, Trp53-ps (transformation related protein 53, pseudogene) [NCBI Gene 22060], NR2E3 (nuclear receptor subfamily 2 group E member 3) [NCBI Gene 10002] {aka ESCS, ESCS1, PNR, RNR, RP37, rd7}, HDAC5 (histone deacetylase 5) [NCBI Gene 10014] {aka HD5, NY-CO-9}, Mir204 (microRNA 204) [NCBI Gene 387200] {aka Mirn204, mir-204, mmu-mir-204}, Mir20a (microRNA 20a) [NCBI Gene 387139] {aka Mir-20, Mirn20, Mirn20a, mir-20a, mmu-mir-20a}, SOCS3 (suppressor of cytokine signaling 3) [NCBI Gene 9021] {aka ATOD4, CIS3, Cish3, SOCS-3, SSI-3, SSI3}, Pou4f2 (POU domain, class 4, transcription factor 2) [NCBI Gene 18997] {aka Brn-3.2, Brn-3b, Brn3b, Pou4f-rs1, mBrn3-3R}, Crx (cone-rod homeobox) [NCBI Gene 12951] {aka Crx1}, Miat (myocardial infarction associated transcript (non-protein coding)) [NCBI Gene 330166] {aka 3632434I06, A230057G18Rik, Rncr2, gomafu}, Mir182 (microRNA 182) [NCBI Gene 387177] {aka Mirn182, mir-182, mmu-mir-182}, Parp1 (poly (ADP-ribose) polymerase family, member 1) [NCBI Gene 11545] {aka 5830444G22Rik, ARTD1, Adprp, Adprt1, PARP, PPOL}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, DNMT1 (DNA methyltransferase 1) [NCBI Gene 396011], Gtf2h4 (general transcription factor II H, polypeptide 4) [NCBI Gene 14885] {aka BTF2 p52, p52}, Dnmt1 (DNA methyltransferase 1) [NCBI Gene 13433] {aka Cxxc9, Dnmt, Dnmt1o, MCMT, MTase, Met-1}, Malat1 (metastasis associated lung adenocarcinoma transcript 1 (non-coding RNA)) [NCBI Gene 72289] {aka 2210401K01Rik, 9430072K23Rik, Neat2}, Neurod4 (neurogenic differentiation 4) [NCBI Gene 11923] {aka ATH-3, Atoh3, MATH-3, Math3, bHLHa4}, HSPA4 (heat shock protein family A (Hsp70) member 4) [NCBI Gene 3308] {aka APG-2, HEL-S-5a, HS24/P52, HSPH2, RY, hsp70}, Trdmt1 (tRNA aspartic acid methyltransferase 1) [NCBI Gene 13434] {aka Dnmt2, Rnmt2, m.MmuIIP, met-2}, Pde4b (phosphodiesterase 4B, cAMP specific) [NCBI Gene 18578] {aka Dpde4, dunce}, Mir18 (microRNA 18) [NCBI Gene 387135] {aka Mirn18, mir-18a, mmu-mir-18, mmu-mir-18a}, RORA (RAR related orphan receptor A) [NCBI Gene 6095] {aka IDDECA, NR1F1, ROR1, ROR2, ROR3, RORa1}, KAT7 (lysine acetyltransferase 7) [NCBI Gene 11143] {aka HBO1, HBOA, MYST2, ZC2HC7}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}, COX2 (cytochrome c oxidase subunit II) [NCBI Gene 17709], IL17F (interleukin 17F) [NCBI Gene 112744] {aka CANDF6, IL-17F, ML-1, ML1}, HPSE2 (heparanase 2 (inactive)) [NCBI Gene 60495] {aka HPA2, HPR2, UFS, UFS1}, POU4F2 (POU class 4 homeobox 2) [NCBI Gene 428735] {aka BRN3.2, BRN3B, Brn-3b, brain-3B}, Rac1 (Rac family small GTPase 1) [NCBI Gene 19353] {aka D5Ertd559e}, Vax2 (ventral anterior homeobox 2) [NCBI Gene 24113] {aka Dres93}, Mir181a-2 (microRNA 181a-2) [NCBI Gene 387176] {aka Mirn181, Mirn181a, Mirn181a-2, miR-181, mir-181a, mir-181a-2}, Hdac4 (histone deacetylase 4) [NCBI Gene 208727] {aka 4932408F19Rik, HD4}, KAT2B (lysine acetyltransferase 2B) [NCBI Gene 8850] {aka CAF, P/CAF, PCAF}, HDAC9 (histone deacetylase 9) [NCBI Gene 9734] {aka HD7, HD7b, HD9, HDAC, HDAC7B, HDAC9B}, SLC2A1 (solute carrier family 2 member 1) [NCBI Gene 6513] {aka CSE, DYT17, DYT18, DYT9, EIG12, GLUT}, Smarca2 (SWI/SNF related BAF chromatin remodeling complex subunit ATPase 2) [NCBI Gene 67155] {aka 2610209L14Rik, SAMRCA2, SNF2alpha, Snf2l2, brahma, brm}, DGCR8 (DGCR8 microprocessor complex subunit) [NCBI Gene 54487] {aka C22orf12, DGCRK6, Gy1, pasha}, Bcl2 (B cell leukemia/lymphoma 2) [NCBI Gene 12043] {aka Bcl-2, C430015F12Rik, D630044D05Rik, D830018M01Rik}, Opn1sw (opsin 1 (cone pigments), short-wave-sensitive (color blindness, tritan)) [NCBI Gene 12057] {aka Bcp}, Pnpla7 (patatin-like phospholipase domain containing 7) [NCBI Gene 241274] {aka E430013P11Rik, Nre}, Abca4 (ATP-binding cassette, sub-family A member 4) [NCBI Gene 11304] {aka Abc10, Abcr, D430003I15Rik, RmP}, RARS1 (arginyl-tRNA synthetase 1) [NCBI Gene 5917] {aka ArgRS, DALRD1, HLD9, RARS}, HDAC7 (histone deacetylase 7) [NCBI Gene 51564] {aka HD7, HD7A, HDAC7A} - **Diseases:** LCA (MESH:D057130), Retinal Disorders (MESH:D012173), RP (MESH:D012174), Inherited retinal degenerative diseases (MESH:D020271), mitochondrial damage (MESH:D028361), drusen (MESH:D015593), AMD (MESH:D008268), retinal degeneration (MESH:D012162), diabetic retinopathy (MESH:D003930), inflammatory degeneration (MESH:D009410), complement factor (CFH) deficiency (MESH:C562875), inherited diseases of the (MESH:D030342), neuroinflammation (MESH:D000090862), inflammation (MESH:D007249), vision loss (MESH:D014786), Retinal Diseases (MESH:D012164), retinoblastoma (MESH:D012175), injury to people or property (MESH:C000719191) - **Chemicals:** cytosine (MESH:D003596), valproic acid (MESH:D014635), 5-methyl cytosine (MESH:D044503), 5-formylcytosine (MESH:C560973), 5-hydroxymethyl cytosine (MESH:C011865), S-adenosyl methionine (MESH:D012436), Tubastatin A (MESH:C553587), vitamin A (MESH:D014801), 5-Aza-2 0-deoxycytidine (-), ATP (MESH:D000255), lipid (MESH:D008055), poly(A) (MESH:D011061), Retinoic acid (MESH:D014212), Zn (MESH:D015032), dinucleotides (MESH:D015226), 5-carboxylcytosine (MESH:C560974), steroid (MESH:D013256), ROS (MESH:D017382), TSA (MESH:C012589), retinoid (MESH:D012176), H2O2 (MESH:D006861), CPG (MESH:C015772), tert-butyl hydroperoxide (MESH:D020122), glucose (MESH:D005947), cholesterol (MESH:D002784) - **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090] - **Mutations:** rs4335725, c.166G>A, rs12900948 - **Cell lines:** retinal — Rattus norvegicus (Rat), Transformed cell line (CVCL_8140), RPE — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_IQ82), ARPE-19 — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_0145) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC10932288/full.md ## Figures 4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC10932288/full.md ## References 103 references — full list in the complete paper: https://tomesphere.com/paper/PMC10932288/full.md --- Source: https://tomesphere.com/paper/PMC10932288