上皮・実質・内皮幹細胞のエピジェネティク分化制御による革新的な三次元的角膜の再生

2013 年度 研究成果報告書

• 研究課題/領域番号: 23689072
• 研究種目: 若手研究(A)
• 配分区分: 補助金
• 研究分野: 眼科学
• 研究機関: 東京女子医科大学 (2012-2013); 東京大学 (2011)
• 研究代表者: 三村 達哉 東京女子医科大学, 医学部, 講師 (70463867)
• 研究期間 (年度): 2011-04-01 – 2014-03-31
• キーワード: 眼発生・再生医学 / エピジェネティクス / 角膜再生

研究概要

老化した細胞や培養細胞ではDNAレベルの変化なしに遺伝子発現が変化するエピジェネティクス化が生じることが近年明らかになっているが角膜疾患については、まだ解明されていない。本研究では角膜組織幹細胞とエピジェネティクス変化を調べた。研究用ヒトドナー角膜の角膜上皮、実質、内皮の各層より細胞を採取し、培養した。また、選択的に未分化な細胞を採取するために、スフェアー法という方法により、角膜上皮、実質、内皮の各層から組織幹細胞/前駆細胞を採取し、メチル化を調べた所、高齢者のドナー由来の角膜の方が、若年者のドナー角膜と比較してメチル化率が高かった。

研究成果

• [雑誌論文] Specific IgE for wheat in tear fluid of patients with allergic conjunctivitis (2014)
  • 著者名/発表者名: Mimura T, Yamagami S, Noma H, Kamei Y, Goto M, Kondo A, Matsubara M
  • 雑誌名: Cutan Ocul Toxicol
• [雑誌論文] Retinal neuroprotective effect of Sirtuins (2014)
  • 著者名/発表者名: Mimura T, Noma H, Funatsu H, Kondo A, Matsubara M
  • 雑誌名: JSM Ophthalmol 巻: 2(1) ページ: 1016
• [雑誌論文] Relationship between total tear IgE and specific serum IgE in autumnal allergic conjunctivitis (2013)
  • 著者名/発表者名: Mimura T, Usui T, Yamagami S, Miyai T, Amano S
  • 雑誌名: Cornea 巻: 32(1) ページ: 14-9
• [雑誌論文] Bilateral eyelid erythema associated with false eyelash glue (2013)
  • 著者名/発表者名: Mimura T
  • 雑誌名: Cutaneous and Ocular Toxicology 巻: 32(1) ページ: 89-90
• [雑誌論文] Association of inflammatory factors with macular edema in branch retinal vein occlusion (2013)
  • 著者名/発表者名: Noma H, Mimura T, Eguchi S
  • 雑誌名: JAMA Ophthalmol 巻: 131(2) ページ: 160-5
• [雑誌論文] Retinal function and morphology in central retinal vein occlusion with macular oedema (2013)
  • 著者名/発表者名: Noma H, Mimura T, Shimada K
  • 雑誌名: Curr Eye Res 巻: 38(1) ページ: 143-9
• [雑誌論文] Changes of inflammatory factors after intravitreal triamcinolone acetonide for macular edema with central retinal vein occlusion (2013)
  • 著者名/発表者名: Noma H, Funatsu H, Mimura T
  • 雑誌名: J Ocul Pharmacol Ther 巻: 29(3) ページ: 363-5
• [雑誌論文] Visual function after pars plana vitrectomy in macular edema with branch retinal vein occlusion (2013)
  • 著者名/発表者名: Noma H, Shimada K, Mimura T
  • 雑誌名: Int Ophthalmol 巻: 33(3) ページ: 227-36
• [雑誌論文] Corneal Endothelial Regeneration and Tissue Engineering (2013)
  • 著者名/発表者名: Mimura T, Yamagami S, Amano S
  • 雑誌名: Prog Retin Eye Res 巻: 35 ページ: 1-17
• [雑誌論文] Changes of macular sensitivity and morphology after pars plana vitrectomy for macular edema with central retinal vein occlusion : a case series (2013)
  • 著者名/発表者名: Noma H, Mimura T, Shimada K
  • 雑誌名: BMC Ophthalmol 巻: 13(1) ページ: 2
• [雑誌論文] Epigenetic regulation of retinal stem cells (2013)
  • 著者名/発表者名: Mimura T, Noma H, Funatsu H
  • 雑誌名: International Journal of Stem Cell Research and Transplantation (IJST) 巻: 103 ページ: 1-2
• [雑誌論文] Influence of axial length on conjunctivochalasis (2013)
  • 著者名/発表者名: Mimura T, Yamagami S, Kamei Y, Goto M, Matsubara M
  • 雑誌名: Cornea 巻: 32(8) ページ: 1126-30
• [雑誌論文] Influence of pars plana vitrectomy on macular sensitivity and morphology in patients with branch retinal vein occlusion and serous retinal detachment (2013)
  • 著者名/発表者名: Noma H, Funatsu H, Shimada K, Mimura T
  • 雑誌名: Ophthalmic Surg Lasers Imaging Retina 巻: 44(2) ページ: 160-7
• [雑誌論文] Influence of retinal ischemia on macular function after pars plana vitrectomy for macular edema with branch retinal vein occlusion (2013)
  • 著者名/発表者名: Noma H, Shimada K, Mimura T
  • 雑誌名: Int Ophthalmol 巻: (Epub ahead of print)
• [雑誌論文] Unilateral macular edema with central retinal vein occlusion in systemic lupus erythematosus : a case report (2013)
  • 著者名/発表者名: Noma H, Shimizu H, Mimura T
  • 雑誌名: Clin Ophthalmol 巻: 7 ページ: 865-867
• [雑誌論文] Specific IgE in tear fluid and features of allergic conjunctivitis (2013)
  • 著者名/発表者名: Mimura T, Yamagami S, Kamei Y, Goto M, Matsubara M
  • 雑誌名: Curr Eye Res 巻: 38(9) ページ: 917-25
• [雑誌論文] Next-generation sequencers : what can we learn? (2013)
  • 著者名/発表者名: Mimura T, Noma H, Funatsu H, Yamagami S
  • 雑誌名: J Bioanal Biomed 巻: 5(2) ページ: 1-3
• [雑誌論文] The role of SIRT1 in ocular aging (2013)
  • 著者名/発表者名: Mimura T, Kaji Y, Noma H, Funatsu H, Okamoto S
  • 雑誌名: Exp Eye Res 巻: 116C ページ: 17-26
• [雑誌論文] Aqueous soluble vascular endothelial growth factor receptor-2 in macular edema with branch retinal vein occlusion (2013)
  • 著者名/発表者名: Noma H, Mimura T
  • 雑誌名: Curr Eye Res
• [雑誌論文] Aqueous flare and inflammatory factors in macular edema with central retinal vein occlusion : a case series (2013)
  • 著者名/発表者名: Noma H, Mimura T, Tatsugawa M, Shimada K
  • 雑誌名: BMC Ophthalmol 巻: 13(1) ページ: 78
• [雑誌論文] Vascular endothelial growth factor and Interleukin-6 are correlated with serous retinal detachment in central retinal vein occlusion (2012)
  • 著者名/発表者名: Noma H, Funatsu H, Mimura T
  • 雑誌名: Curr Eye Res 巻: 37(1) ページ: 62-7
• [雑誌論文] Vitreous inflammatory factors and macular oedema (2012)
  • 著者名/発表者名: Funatsu H, Noma H, Mimura T, Eguchi S
  • 雑誌名: Br J Ophthalmol 巻: 96(2) ページ: 302-4
• [雑誌論文] Conjunctivochalasis : associations with pinguecula in a hospital-based study (2012)
  • 著者名/発表者名: Mimura T, Mori M, Obata H, Usui T, Yamagami S, Funatsu H, Noma H, Amano S
  • 雑誌名: Acta Ophthalmol 巻: 90(8) ページ: 773-782
• [雑誌論文] Pinguecula and diabetes mellitus (2012)
  • 著者名/発表者名: Mimura T, Obata H, Usui T, Mori M, Yamagami S, Funatsu H, Noma H, Amano S
  • 雑誌名: Cornea 巻: 31(3) ページ: 264-8
• [雑誌論文] Vitreous Inflammatory Factors and Serous Macular Detachment in Branch Retinal Vein Occlusion (2012)
  • 著者名/発表者名: Noma H, Funatsu H, Mimura T, Tatsugawa M, Shimada K, Eguchi S
  • 雑誌名: Retina 巻: 32(1) ページ: 86-91
• [雑誌論文] Inflammatory factors in major and macular branch retinal vein occlusion (2012)
  • 著者名/発表者名: Noma H, Funatsu H, Mimura T, Eguchi S, Shimada K
  • 雑誌名: Ophthalmologica 巻: 227(3) ページ: 146-52
• [雑誌論文] Vascular endothelial growth factor receptor-2 in macular oedema with retinal vein occlusion (2012)
  • 著者名/発表者名: Noma H, Funatsu H, Mimura T, Eguchi S
  • 雑誌名: Ophthalmic Res 巻: 48(1) ページ: 56-58
• [雑誌論文] Bilateral choroidal detachment after cord blood stem cell transplantation in an adult patient with acute myeloid leukemia (2012)
  • 著者名/発表者名: Mimura T, Nakashizuka T, Kami J, Kohmura M, Sato S, Dou K, Mori M
  • 雑誌名: Int Ophthalmol 巻: 32(4) ページ: 379-81
• [雑誌論文] Functional-morphological changes after intravitreal injection of triamcinolone acetonide for macular edema with branch retinal vein occlusion (2012)
  • 著者名/発表者名: Noma H, Funatsu H, Mimura T, Shimada K
  • 雑誌名: J Ocul Pharmacol Ther 巻: 28(3) ページ: 231-6
• [雑誌論文] Relation between Total Tear IgE and Severity of Acute Seasonal Allergic Conjunctivitis (2012)
  • 著者名/発表者名: Mimura T, Usui T, Yamagami S, Miyai T, Amano S
  • 雑誌名: Curr Eye Res 巻: 37(10) ページ: 864-70
• [雑誌論文] Pigment epithelium-derived factor is related to macular microcirculation in patients with macular edema and branch retinal vein occlusion (2012)
  • 著者名/発表者名: Noma H, Funatsu H, Mimura T
  • 雑誌名: Int Ophthalmol 巻: 32(5) ページ: 485-9
• [雑誌論文] Macular sensitivity and morphology after intravitreal injection of triamcinolone acetonide for macular edema with branch retinal vein occlusion (2012)
  • 著者名/発表者名: Noma H, Funatsu H, Mimura T, Shimada K
  • 雑誌名: Retina 巻: 32(9) ページ: 1844-52
• [雑誌論文] Perifoveal Microcirculation in Macular Oedema with Retinal Vein Occlusion (2012)
  • 著者名/発表者名: Noma H, Funatsu H, Mimura T, Shimada K
  • 雑誌名: Open Ophthalmol J 巻: 6 ページ: 63-64
• [雑誌論文] Comparison of the efficacy of intravitreal triamcinolone acetonide for cystoid macular edema with versus without serous retinal detachment in branch retinal vein occlusion : influence on macular sensitivity and morphology (2012)
  • 著者名/発表者名: Noma H, Funatsu H, Mimura T, Shimada K
  • 雑誌名: BMC Ophthalmol 巻: 12(1) ページ: 39
• [雑誌論文] Association of electroretinographic parameters and inflammatory factors in branch retinal vein occlusion with macular oedema (2012)
  • 著者名/発表者名: Noma H, Funatsu H, Mimura T
  • 雑誌名: Br J Ophthalmol 巻: 96(12) ページ: 1489-93
• [雑誌論文] Development of surgical treatment for vitreous disease (2012)
  • 著者名/発表者名: Mimura T, Noma H, Funatsu H
  • 雑誌名: Surgical Science 巻: 3(11) ページ: 507-513
• [雑誌論文] Tissue engineering of corneal endothelium (2012)
  • 著者名/発表者名: Mimura T, Yokoo S, Yamagami S
  • 雑誌名: J. Funct. Biomater 巻: 3(4) ページ: 726-744
• [雑誌論文] Use of the femtosecond laser for cataract surgery with intraocular lens implantation (2012)
  • 著者名/発表者名: Mimura T, Yamazaki K
  • 雑誌名: J Transplant Technol Res 巻: 2 ページ: e116
• [雑誌論文] Macular sensitivity and morphology after intravitreal injection of triamcinolone acetonide for macular edema secondary to central retinal vein occlusion (2012)
  • 著者名/発表者名: Noma H, Mimura T
  • 雑誌名: Clin Ophthalmol 巻: 6 ページ: 1901-6
• [雑誌論文] Foveal Sensitivity and Morphology in Major and Macular Branch Retinal Vein Occlusion (2012)
  • 著者名/発表者名: Noma H, Shimada K, Mimura T
  • 雑誌名: Open Ophthalmol J 巻: 6 ページ: 104-9
• [雑誌論文] Visual Accommodation and Advances in Management of Presbyopia (2012)
  • 著者名/発表者名: Mimura T, Noma H, Yamagami S
  • 雑誌名: Biol Syst 巻: 2 ページ: 107
• [雑誌論文] Visual function and serous retinal detachment in patients with branch retinal vein occlusion and macular edema : a case series (2011)
  • 著者名/発表者名: Noma H, Funatsu H, Mimura T, Shimada K
  • 雑誌名: BMC Ophthalmol 巻: 11(1) ページ: 29
• [雑誌論文] Recent advances and history of vitreous surgery (2011)
  • 著者名/発表者名: Mimura T, Nakashizuka T, Mori M
  • 雑誌名: Journal of Healthcare Engineering 巻: 2(4) ページ: 447–458
• [雑誌論文] Influence of vitreous factors after vitrectomy for macular edema in patients with central retinal vein occlusion (2011)
  • 著者名/発表者名: Noma H, Funatsu H, Mimura T, Eguchi S, Shimada K
  • 雑誌名: Int Ophthalmol 巻: 31(5) ページ: 393-402
• [雑誌論文] Prospects for Descemet stripping automated endothelial keratoplasty using cultured human corneal endothelial cells (2011)
  • 著者名/発表者名: Mimura T, Yamagami S, Yokoo S, Usui T, Amano S
  • 雑誌名: J Transplant Technol Res S2-001
• [雑誌論文] Vitreous inflammatory factors and serous retinal detachment in central retinal vein occlusion : a case control series (2011)
  • 著者名/発表者名: Noma H, Funatsu H, Mimura T, Eguchi S
  • 雑誌名: J Inflamm (Lond) 巻: 8(1) ページ: 38
• [雑誌論文] Laser treatment of giant iris cyst with nanophthalmos (2011)
  • 著者名/発表者名: Honda N, Mimura T, Hotehama A, Usui T, Sugisaki K, Fukuoka S, Amano S
  • 雑誌名: Int Ophthalmol 巻: 31(1) ページ: 17-20
• [雑誌論文] Relationship between total tear and serum IgE in allergic conjunctivitis (2011)
  • 著者名/発表者名: Mimura T, Usui T, Mori M, Funatsu H, Noma H, Yamamoto H, Aixinjueluo W, Amano S
  • 雑誌名: Int Arch Allergy Immunol 巻: 154(4) ページ: 349-52
• [雑誌論文] Rapid immunochromatographic measurement of specific tear IgE in moderate to severe cases of allergic conjunctivitis with immfast check J1 in the spring (2011)
  • 著者名/発表者名: Mimura T, Usui T, Mori M, Funatsu H, Noma H, Amano S
  • 雑誌名: Cornea 巻: 30(5) ページ: 524-7
• [雑誌論文] Vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor in macular edema with central retinal vein occlusion (2011)
  • 著者名/発表者名: Noma H, Funatsu H, Mimura T, Eguchi S, Shimada K, Hori S
  • 雑誌名: Curr Eye Res 巻: 36(3) ページ: 256-63
• [雑誌論文] Severity and determinants of pinguecula in a hospital-based population (2011)
  • 著者名/発表者名: Mimura T, Usui T, Obata H, Yamagami S, Mori M, Funatsu H, Noma H, Dou K, Amano S
  • 雑誌名: Eye Contact Lens 巻: 37(1) ページ: 31-35
• [雑誌論文] Sudden onset of amantadine-induced reversible bilateral corneal edema in an elderly patient : Case report and literature review (2011)
  • 著者名/発表者名: Hotehama A, Mimura T, Usui T, Kawashima H, Amano S
  • 雑誌名: Jpn J Ophthalmol 巻: 55(1) ページ: 71-74
• [雑誌論文] Relation between total tear IgE and specific serum IgE in seasonal allergic conjunctivitis (2011)
  • 著者名/発表者名: Mimura T, Usui T, Mori M, Funatsu H, Noma H, Yamamoto H, Aixinjueluo W, Amano S
  • 雑誌名: Cornea 巻: 30(7) ページ: 790-5
• [雑誌論文] Role of soluble vascular endothelial growth factor receptor-2 in macular oedema with central retinal vein occlusion (2011)
  • 著者名/発表者名: Noma H, Funatsu H, Mimura T, Eguchi S, Shimada K
  • 雑誌名: Br J Ophthalmol 巻: 95(6) ページ: 788-92
• [雑誌論文] Visual prognosis and vitreous molecules after vitrectomy for macular edema with branch retinal vein occlusion (2011)
  • 著者名/発表者名: Noma H, Funatsu H, Mimura T, Eguchi S, Shimada K
  • 雑誌名: Clin Ophthalmol 巻: 5 ページ: 223-9
• [雑誌論文] Relationship between conjunctivochalasis and refractive error (2011)
  • 著者名/発表者名: Mimura T, Usui T, Yamagami S, Funatsu H, Noma H, Toyono T, Mori M, Amano S
  • 雑誌名: Eye Contact Lens 巻: 37(2) ページ: 71-8
• [雑誌論文] Specific tear IgE in patients with moderate-to-severe autumnal allergic conjunctivitis (2011)
  • 著者名/発表者名: Mimura T, Usui T, Mori M, Funatsu H, Noma H, Amano S
  • 雑誌名: Int Arch Allergy Immunol 巻: 156(4) ページ: 381-386
• [雑誌論文] Functional-morphological correlates in patients with branch retinal vein occlusion and macular edema (2011)
  • 著者名/発表者名: Noma H, Funatsu H, Mimura T, Harino S, Shimada K
  • 雑誌名: Retina 巻: 31(10) ページ: 2102-8
• [雑誌論文] Effect of trabeculectomy on ocular and corneal higher order aberrations (2011)
  • 著者名/発表者名: Fukuoka S, Amano S, Honda N, Mimura T, Usui T, Araie M
  • 雑誌名: Jpn J Ophthalmol 巻: 55(5) ページ: 460-6
• [雑誌論文] Soluble vascular endothelial growth factor receptor-2 and inflammatory factors in macular edema with branch retinal vein occlusion (2011)
  • 著者名/発表者名: Noma H, Funatsu H, Mimura T, Eguch S, Hori S
  • 雑誌名: Am J Ophthalmol 巻: 152(4) ページ: 669-677.e1
• [雑誌論文] Asymptomatic subconjunctival entrapment of a cilium (2011)
  • 著者名/発表者名: Mimura T, Nakashizuka T, Kami J, Kohmura M, Sato S, Dou K, Mori M
  • 雑誌名: Int Ophthalmol 巻: 31(4) ページ: 325-6
• [雑誌論文] Influence of ischemia on visual function in patients with branch retinal vein occlusion and macular edema (2011)
  • 著者名/発表者名: Noma H, Funatsu H, Mimura T, Shimada K
  • 雑誌名: Clin Ophthalmol 巻: 5 ページ: 679–685
• [雑誌論文] Association of electroretinogram and morphological findings in branch retinal vein occlusion with macular edema (2011)
  • 著者名/発表者名: Noma H, Funatsu H, Harino S, Sugawara T, Mimura T, Shimada K
  • 雑誌名: Doc Ophthalmol 巻: 123(2) ページ: 83-91
• [雑誌論文] Measurement of Specific Tear IgE With ImmunoCAP Rapid
  • 著者名/発表者名: Mimura T, Yamagami S, Kamei Y, Goto M, Kondo A, Matsubara M
  • 雑誌名: Journal of Investigational Allergology and Clinical Immunology 巻: (in press)
• [雑誌論文] Shimada Pentraxin 3 and other inflammatory factors in central retinal vein occlusion and macular edema
  • 著者名/発表者名: Noma H, Mimura T, Masahara H
  • 雑誌名: Retina 巻: (in press)
• [雑誌論文] Conjunctival sensitization to hydrolyzed wheat protein in facial soap
  • 著者名/発表者名: Mimura T, Noma H, Yamagami S
  • 雑誌名: J Investig Allergol Clin Immunol 巻: (in press)
• [雑誌論文] Shimada Role of inflammation in macular edema with branch retinal vein occlusion
  • 著者名/発表者名: Noma H, Funatsu H, Mimura T
  • 雑誌名: Curr Eye Res 巻: (in press)
• [雑誌論文] Association of electroretinogram and morphological findings in central retinal vein occlusion with macular edema
  • 著者名/発表者名: Noma H, Mimura T, Kuse M, Shimada K
  • 雑誌名: Clin Ophthalmol 巻: (in press)
• [雑誌論文] Vascular endothelial growth factor and its soluble receptors-1 and -2 in iris neovascularization and neovascular glaucoma
  • 著者名/発表者名: Noma H, Mimura T, Yasuda K, Shimura M
  • 雑誌名: Ophthalmologica 巻: (in press)
• [学会発表] 角膜内皮の老化と再生 (2013)
  • 著者名/発表者名: 三村達哉
  • 学会等名: 第80回東京女子医大東医療センター眼科医局講演会特別講演
  • 発表場所: 東京
  • 年月日: 2013-10-12
• [学会発表] ヒト角膜内皮細胞の全ゲノム解析によるDNAメチル化プロファイル角膜カンファランス (2013)
  • 著者名/発表者名: 三村達哉、中川卓、山上聡、天野史郎
  • 学会等名: 第29回日本角膜移植学会
  • 発表場所: 南紀白浜
  • 年月日: 2013-02-14
• [図書] Transplantation of corneal stroma reconstructed with gelatin and multipotent precursor cells from corneal stroma(In : Daniel Eberli, editor. Regenerative Medicine and Tissue Engineering; From Cells to Organs)(ISBN 978-953-307-688-1) (2011)
  • 著者名/発表者名: Mimura T, Tabata Y, Amano S
  • 総ページ数: 347-362
  • 出版者: InTech
• [図書] Corneal endothelial tissue bioengineering using cultured human corneal endothelial precursor cells(In : Jose A. Andrades, editor. Chapter 18, Regenerative Medicine and Tissue Engineering)(ISBN 978-953-51-1108-5)
  • 著者名/発表者名: Mimura T, Yokoo S, Yamagami S
  • 総ページ数: 429-451
  • 出版者: InTech