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

2010 Fiscal Year Final Research Report

• Project/Area Number: 20592054
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Kyoto 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
• Keywords: 再生医療 / 角膜上皮 / 口腔粘膜上皮 / 血管新生 / 眼表面再建

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.

Research Products

• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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)
• [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
• [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
• [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
• [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.
• [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
• [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
• [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
• [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
• [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
• [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