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The Development of the regenerated mucosal epithelial transplantation for immunomodulation and ocular surface reconstruction.

Research Project

Project/Area Number 20592054
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

INATOMI Tsutomu  Kyoto Prefectural University of Medicine, 医学研究科, 助教 (00305583)

Co-Investigator(Kenkyū-buntansha) KAWASAKI Satoshi  京都府立医科大学, 医学研究科, 助教 (60347458)
MARUYAMA Kazuichi  京都府立医科大学, 医学研究科, 助教 (10433244)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords再生医療 / 角膜上皮 / 口腔粘膜上皮 / 血管新生 / 眼表面再建 / 口腔粘膜 / ムチン / 粘膜免疫
Research Abstract

We have successfully generated cultivated corneal epithelial sheet and oral mucosal epithelial sheet which are applicable for ocular surface reconstruction. These epithelial sheets expressed p75 in the basal region suggesting the high potential for cell proliferation. Ectopicallysurvived oral mucosal epithelium on the cornea expressed neither PAX6 gene nor K1 and K10. However,these cells expressed K4, K3 and K13, but not K12. The phenotype of surviving transplanted oral mucosal epithelium on the cornea was the same as in vivo oral mucosal epithelium, suggesting that cultivated oral mucosal epithelium does not transdifferentiate into corneal epithelium. Peripheralneovascularization and lymphanogenesis were induced in early post-operative phase. In vivo confocal microscopic analysis revealed well-organized stratified epithelium containing the proper cell density of basal cells and flattened apical cells. Anti-VEGF treatment could inhibit the progression of vessels and control the phenotype of surviving epithelial cells on the ocular surface.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (33 results)

All 2010 2009 2008 Other

All Journal Article (24 results) (of which Peer Reviewed: 6 results) Presentation (9 results)

  • [Journal Article] A significant association of viral loads with corneal endothelial cell damage in cytomegalovirus anterior uveitis.2010

    • Author(s)
      Miyanaga M, Sugita S, Shimizu N, Morio T, Miyata K, Maruyama K, Kinoshita S, Mochizuki M.
    • Journal Title

      Br J Ophthalmol 94(3)

      Pages: 336-340

    • Related Report
      2010 Final Research Report
  • [Journal Article] Lymphangiogenesis and angiogenesis : concurrence and/or dependence? Studies in inbred mouse strains.2010

    • Author(s)
      Nakao S, Maruyama K, Zandi S, Melhorn MI, Taher M, Noda K, Nusayr E, Doetschman T, Hafezi-Moghadam A.
    • Journal Title

      FASEB J. 24(2)

      Pages: 504-513

    • Related Report
      2010 Final Research Report
  • [Journal Article] The relationship between preoperative clinical scores and immunohistological evaluation of surgically resected tissues in chronic severe ocular surface diseases.2010

    • Author(s)
      Tanioka H, Kawasaki S, Sotozono C, Nakamura T, Inatomi T, Kinoshita S.
    • Journal Title

      Jpn J Ophthalmol. 54

      Pages: 66-73

    • NAID

      10027203534

    • Related Report
      2010 Final Research Report
  • [Journal Article] Tumor-associated calcium signal transducer 2 is required for the proper subcellular localization of claudin 1 and 7 : implications in the pathogenesis of gelatinous drop-like corneal dystrophy.2010

    • Author(s)
      Nakatsukasa M, Kawasaki S, Yamasaki K, Fukuoka H, Matsuda A, Tsujikawa M, Tanioka H, Nagata-Takaoka M, Hamuro J, Kinoshita S.
    • Journal Title

      Am J Pathol. 177

      Pages: 1344-1355

    • Related Report
      2010 Final Research Report
  • [Journal Article] Basophils in the giant papillae of chronic allergic keratoconjunctivitis.2010

    • Author(s)
      Matsuda A, Ebihara N, Yokoi N, Okayama Y, Watanabe Y, Kawasaki S, Tanioka H, Walls AF, Hamuro J, Kinoshita S, Murakami A.
    • Journal Title

      Br J Ophthalmol. 94

      Pages: 513-518

    • Related Report
      2010 Final Research Report
  • [Journal Article] A novel mutation of the TGFBI gene causing a lattice corneal dystrophy with deep stromal involvement.2010

    • Author(s)
      Kawasaki S, Yagi H, Yamasaki K, Matsuda A, Takeda K, Kinoshita S.
    • Journal Title

      Br J Ophthalmol. 95

      Pages: 150-151

    • Related Report
      2010 Final Research Report
  • [Journal Article] Lattice corneal dystrophy type IV (p.Leu527Arg) is caused by a founder mutation of the TGFBI gene in a single Japanese ancestor.2010

    • Author(s)
      Fukuoka H, Kawasaki S, Yamasaki K, Matsuda A, Fukumoto A, Murakami A, Kinoshita S.
    • Journal Title

      Invest Ophthalmol Vis Sci. 51

      Pages: 4523-4530

    • Related Report
      2010 Final Research Report
  • [Journal Article] Association between prostaglandin E receptor 3 polymorphisms and Stevens-Johnson syndrome identified by means of a genome-wide association study.2010

    • Author(s)
      Ueta M, Sotozono C, Nakano M, Taniguchi T, Yagi T, Tokuda Y, Fuwa M, Inatomi T, Yokoi N, Tashiro K, Kinoshita S.
    • Journal Title

      J Allergy Clin Immunol. 126(6)

      Pages: 1218-1225

    • Related Report
      2010 Final Research Report
  • [Journal Article] Prostaglandin E receptor 4 expression in human conjunctival epithelium and its downregulation in devastating ocular surface inflammatory disorders.2010

    • Author(s)
      Ueta M, Sotozono C, Yokoi N, Inatomi T, Kinoshita S.
    • Journal Title

      Arch Ophthalmol. 128(10)

      Pages: 1369-1371

    • Related Report
      2010 Final Research Report
  • [Journal Article] Long-Term Phenotypic Study after Allogeneic Cultivated Corneal Limbal Epithelial Transplantation for Severe Ocular Surface Diseases.2010

    • Author(s)
      Nakamura T, Sotozono C, Bentley AJ, Mano S, Inatomi T, Koizumi N, Fullwood NJ, Kinoshita S.
    • Journal Title

      Ophthalmology 117(12)

      Pages: 2247-2254

    • Related Report
      2010 Final Research Report
  • [Journal Article] Cultivated human conjunctival epithelial transplantation for total limbal stem cell deficiency.2010

    • Author(s)
      Ang LP, Tanioka H, Kawasaki S, Ang LP, Yamasaki K, Do TP, Thein ZM, Koizumi N, Nakamura T, Yokoi N, Komuro A, Inatomi T, Nakatsukasa M, Kinoshita S.
    • Journal Title

      Invest Ophthalmol Vis Sci. 51(2)

      Pages: 758-764

    • Related Report
      2010 Final Research Report
  • [Journal Article] Long-term results of autologous cultivated oral mucosal epithelial transplantation in the scar phase of severe ocular surface disorders.2010

    • Author(s)
      Nakamura T, Takeda K, Inatomi T, Sotozono C, Kinoshita S.
    • Journal Title

      Br J Ophthalmol. (2010 Nov 19. Epub)

    • Related Report
      2010 Final Research Report
  • [Journal Article] Long-term results of autologous cultivated oral mucosal epithelial transplantation in the sear phase of severe ocular surface disorders.2010

    • Author(s)
      Nakamura T, Inatomi T, et al
    • Journal Title

      Br J Ophthalmol

      Volume: (Epub)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-term phenotypic study after allogeneic cultivated comeal limbal epithelial transplantation for severe ocular surface diseases.2010

    • Author(s)
      Nakamura T, Inatomi T, et al
    • Journal Title

      Ophthalmology

      Volume: 117(12) Pages: 2247-2254

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The relationship between preoperative clinical scores and immunohistological evaluation of surgically resected tissues in chronic severe ocular surface diseases.2010

    • Author(s)
      Tanioka H, Inatomi T, et al
    • Journal Title

      Jpn J Ophthalmol

      Volume: 54(1) Pages: 66-73

    • NAID

      10027203534

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The relationship between preoperative clinical scores and immunohistological evaluation of surgically resected tissues in chronic severe ocular surface diseases.2010

    • Author(s)
      Tanioka H, Inatomi T, et al
    • Journal Title

      Jpn J Ophthalmol 54(1)

      Pages: 66-73

    • NAID

      10027203534

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cultivated human conjunctival epithelial transplantation for total limbal stem cell deficiency.2010

    • Author(s)
      Ang LP, Inatomi T, et al
    • Journal Title

      Invest Ophthalmol Vis Sci 51(2)

      Pages: 758-764

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Diagnosis and treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis with ocular complications.2009

    • Author(s)
      Sotozono C, Ueta M, Koizumi N, Inatomi T, Shirakata Y, Ikezawa Z, Hashimoto K, Kinoshita S.
    • Journal Title

      Ophthalmology 116(4)

      Pages: 685-690

    • Related Report
      2010 Final Research Report
  • [Journal Article] Genomic aberrations and cellular heterogeneity in SV40-immortalized human corneal epithelial cells.2009

    • Author(s)
      Yamasaki K, Kawasaki S, Young RD, Fukuoka H, Tanioka H, Nakatsukasa M, Quantock AJ, Kinoshita S.
    • Journal Title

      Invest Ophthalmol Vis Sci. 50

      Pages: 604-613

    • Related Report
      2010 Final Research Report
  • [Journal Article] Investigation of the corneal filament in filamentary keratitis.2009

    • Author(s)
      Tanioka H, Yokoi N, Komuro A, Shimamoto T, Kawasaki S, Matsuda A, Kinoshita S.
    • Journal Title

      Invest Ophthalmol Vis Sci. 50

      Pages: 3696-3702

    • Related Report
      2010 Final Research Report
  • [Journal Article] Diagnosis and treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis with ocular complications.2009

    • Author(s)
      Sotozono C.Inatomi T, et al
    • Journal Title

      Ophthalmology 116(4)

      Pages: 685-690

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Current progress and challenges in ocular surface reconstruc tion using cultivated epithelial sheet transplantation2008

    • Author(s)
      Inatomi T, et al
    • Journal Title

      Med J Malaysia 63

      Pages: 42-42

    • Related Report
      2008 Annual Research Report
  • [Journal Article] Surgery of the conjunctiva2008

    • Author(s)
      Yokoi N, Inatomi T Kinoshita S
    • Journal Title

      Dev Ophthalmol 41

      Pages: 138-58

    • Related Report
      2008 Annual Research Report
  • [Journal Article] Characteristic appearance of early-stage Acanthamoeba keratitis.

    • Author(s)
      Sasaki M, Sotozono C, Chihara H, Ueta M, Inatomi T, Yokoi N, Shiota T, Kinoshita S.
    • NAID

      10029366964

    • Related Report
      2010 Final Research Report
  • [Presentation] Application of Cultivated Oral Mucosal Epithelial Transplantation for Ocular Surface Reconstruction.2010

    • Author(s)
      T Inatomi
    • Organizer
      2nd Asia Cornea Society Biennial Scientific Meeting.
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2010-12-02
    • Related Report
      2010 Final Research Report
  • [Presentation] The proper Treatment of Acanthamoeba Keratitis in CL users.2010

    • Author(s)
      T Inatomi
    • Organizer
      2nd Asia Cornea Society Biennial Scientific Meeting.
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2010-12-02
    • Related Report
      2010 Final Research Report
  • [Presentation] Cultivated Oral Mucosal Epithelial Transplantation for Ocular Surface Reconstruction.2010

    • Author(s)
      T Inatomi
    • Organizer
      25th APAO Congress.
    • Place of Presentation
      Beijing, China
    • Year and Date
      2010-09-19
    • Related Report
      2010 Final Research Report
  • [Presentation] Cultivated Oral Mucosal Epithelial Transplantation(COMET)for Oculaz Suface Reconstruction2010

    • Author(s)
      Inatomi T, et al
    • Organizer
      Asia Pacific Academy of Ophthalmology
    • Place of Presentation
      北京 中国
    • Year and Date
      2010-09-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] Ex vivo expansion of mucoasl epithelium for ocular surface diseases.2010

    • Author(s)
      T Inatomi, T Nakamura, N Koizumi, C Sotozono, S Kinoshita
    • Organizer
      World Ophthalmology Congress 2010
    • Place of Presentation
      Berlin, Germany
    • Year and Date
      2010-06-10
    • Related Report
      2010 Final Research Report
  • [Presentation] Corneal Endothelial Cell Loss and Graft Thickness Following Descemet-Stripping Automated Endothelial Keratoplasty.2010

    • Author(s)
      T Inatomi, H Adachi, H Tanioka, O Hieda, S Kinoshita
    • Place of Presentation
      ARVO, Fort Lauderdel, USA.
    • Year and Date
      2010-05-02
    • Related Report
      2010 Final Research Report
  • [Presentation] Clinical Outcomes of Descemet-Stripping Automated Endothelial Keratoplasty for Bullous Keratopathy with Pre-Existing Glaucoma.2010

    • Author(s)
      T Inatomi, H Adachi, K Mori, H Tanioka, O Hieda, S Kinoshita
    • Organizer
      World Corneal Cogress VI
    • Place of Presentation
      Boston, USA
    • Year and Date
      2010-04-07
    • Related Report
      2010 Final Research Report
  • [Presentation] Conjunctival Reconstruction using cultivated autologous oral mucosal epithelial transplantation2009

    • Author(s)
      Inatomi T, et al
    • Organizer
      American Academy Ophthalmology
    • Place of Presentation
      San Francisco USA
    • Year and Date
      2009-10-23
    • Related Report
      2009 Annual Research Report
  • [Presentation] Phenotypic analysis of cultivated oral mucosal epithelium transplanted on a human cornea2009

    • Author(s)
      Inatomi T, et al
    • Organizer
      Association for Research in Vision and Ophthalmology
    • Place of Presentation
      Florida USA
    • Year and Date
      2009-05-07
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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