The development of new treatments for intractable neuroparalytic corneal epithelial disorder in TRP channel control.

• Project/Area Number: 24791869
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: Wakayama Medical University
• Principal Investigator: SUMIOKA TAKAYOSHI 和歌山県立医科大学, 医学部, 講師 (40433362)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: TRPV1 / 角膜上皮創傷治癒 / 角膜創傷治癒 / 角膜上皮 / 角膜実質 / TRPV１ / テネイシンC / テネイシンX / 創傷治癒 / TRPチャンネル / NOS2

Outline of Final Research Achievements

TRPV1 was detected mainly in the basal layer of mouse or rat corneal epithelium. Adding a TRPV1 receptor agonist to the culture medium enhanced epithelial healing in the rat cornea, and a TRPV1 antagonist retarded it in organ culture. The loss of TRPV1 did not affect the histology of the mouse cornea. In vivo analysis showed the loss of TRPV1-impaired re-epithelialization of the debrided area of the corneal epithelium by the suppression of both cell migration and proliferation. The lack of TRPV1 suppressed the expression of IL-6 and substance P but not of TGF-β1 in response to epithelial debridement in mice. TRPV1 signal is required for the upregulation of IL-6 and substance P and the healing of debrided corneal epithelium in mice.

Research Products

• [Journal Article] A Case of Solitary Nonvascularized Corneal Epithelial Dysplasia. (2016)
  • Author(s): Morii T, Sumioka T, Izutani-Kitano A, Takada Y, Okada Y, Kao WW, Saika S.
  • Journal Title: Case Rep Ophthalmol Med. Volume: 5687285 Pages: 5687285-5687285
  • DOI: 10.1155/2016/5687285
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Modulation of Smad signaling by non-TGFβ components in myofibroblast generation during wound healing in corneal stroma. (2016)
  • Author(s): Saika S, Yamanaka O, Okada Y, Sumioka T.
  • Journal Title: Exp Eye Res. Volume: 142 Pages: 40-48
  • DOI: 10.1016/j.exer.2014.12.015
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Suppression of In Vivo Neovascularization by the Loss of TRPV1 in Mouse Cornea. (2015)
  • Author(s): Tomoyose K, Okada Y, Sumioka T, Miyajima M, Flanders KC, Shirai K, Morii T, Reinach PS, Yamanaka O, Saika S.
  • Journal Title: J Ophthalmol. Volume: Sep 27 Pages: 706404-706404
  • DOI: 10.1155/2015/706404
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transient Receptor Potential Channels and Corneal Stromal Inflammation. (2015)
  • Author(s): 0kada Y,Reinach PS,Shirai K,Kitano-Izutani A,Miyajima M,Yamanaka O,Sumioka T, Saika S
  • Journal Title: Cornea Volume: Suppl 11 Issue: Supplement 11 Pages: 136-41
  • DOI: 10.1097/ico.0000000000000602
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Impairment of corneal epithelial wound healing in a TRPV1-deficient mouse. (2014)
  • Author(s): Sumioka T, Okada Y, Reinach PS, Shirai K, Miyajima M, Yamanaka O, Saika S.
  • Journal Title: Invest Ophthalmol Vis Sci. Volume: 55 Issue: 5 Pages: 3295-3302
  • DOI: 10.1167/iovs.13-13077
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Temperature-sensitive transient receptor potential channels in corneal tissue layers and cells. (2014)
  • Author(s): Mergler S1, Valtink M, Takayoshi S, Okada Y, Miyajima M, Saika S, Reinach PS.
  • Journal Title: Ophthalmic Res. Volume: 52 Issue: 3 Pages: 151-159
  • DOI: 10.1159/000365334
  • Peer Reviewed / Open Access
• [Journal Article] Histological analysis of a cornea following experimental femtosecond laser ablation. (2014)
  • Author(s): Sumioka T, Miyamoto T, Takatsuki R, Okada Y, Yamanaka O, Saika S.
  • Journal Title: Cornea. Volume: 33 Issue: Supplement 11 Pages: 19-24
  • DOI: 10.1097/ico.0000000000000251
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The role of extracellular matrix in corneal wound healing. (2013)
  • Author(s): Yamanaka O, Sumioka T, Saika S.
  • Journal Title: Cornea Volume: 32 Issue: Supplement 1 Pages: S43-S45
  • DOI: 10.1097/ico.0b013e3182a4786b
  • Peer Reviewed
• [Journal Article] Impaired cornea wound healing in a tenascin C-deficient mouse model (2012)
  • Author(s): Sumioka T, Kitano A, Flanders KC, Okada Y, Yamanaka O, Fujita N, Iwanishi H, Kao WW, Saika S
  • Journal Title: Lab Invest Volume: 93(2) Issue: 2 Pages: 207-17
  • DOI: 10.1038/labinvest.2012.157
  • Peer Reviewed
• [Presentation] Loss of tenascin X impaired neovascularization in cornea in response to injury in mice (2016)
  • Author(s): Takayoshi Sumioka, Yuka Okada, Yuka Nidegawa, Masayasu Miyajima, Ken-ichi Matsumoto, Shizuya Saika
  • Organizer: Gordon Con
  • Place of Presentation: Denver, USA
  • Year and Date: 2016-02-28
  • Int'l Joint Research
• [Presentation] Lacking tenascin X impaired neovascularization in cornea in response to injury in mice (2016)
  • Author(s): Takayoshi Sumioka, Yuka Okada, Yuka Nidegawa, Masayasu Miyajima, Ken-ichi Matsumoto, Shizuya Saika
  • Organizer: Keystone Symposia 2016
  • Place of Presentation: Denver, USA
  • Year and Date: 2016-02-07
  • Int'l Joint Research
• [Presentation] Attenuated neovascularization in a tenascin X-null mouse in response to injury (2015)
  • Author(s): Takayoshi Sumioka, Yuka Okada, Yuka Nidegawa, Masayasu Miyajima, Ken-ichi Matsumoto, Shizuya Saika1
  • Organizer: PPCTSS2015
  • Place of Presentation: ソウル，韓国
  • Year and Date: 2015-08-24
  • Int'l Joint Research
• [Presentation] マウス創傷角膜ではテネイシンX欠失でVEGF発現や血管新生を抑制する (2015)
  • Author(s): 住岡孝吉、岡田由香、二出川裕香、宮嶋正康、 松本健一、雑賀司珠也
  • Organizer: 第47回 日本結合組織学会
  • Place of Presentation: 三重
  • Year and Date: 2015-05-16
• [Presentation] Loss of tenascin X suppresses expression of VEGF in macrophages and of TGFb1 in ocular fibroblasts in vitro; possible mechanism of inhibition of neovascularization in cornea (2015)
  • Author(s): Takayoshi Sumioka, Yuka Okada, Ken-ichi Matsumoto, Osamu Yamanaka, Masayasu Miyajima, Shizuya Saika.
  • Organizer: ARVO2015
  • Place of Presentation: Denver, USA
  • Year and Date: 2015-05-03
  • Int'l Joint Research
• [Presentation] 培養マクロファージと線維芽細胞の 成長因子発現でのテネイシンXの役割 (2015)
  • Author(s): 住岡孝吉、岡田由香、山中 修、松本健一、宮嶋正康、雑賀司珠也
  • Organizer: 第119回 日本眼科学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2015-04-16
• [Presentation] Impaired angiogenic response in cornea by lacking tenascin X . (2015)
  • Author(s): Takayoshi Sumioka, Yuka Okada, Yuka Nidegawa, Masayasu Miyajima, Ken-ichi Matsumoto, Shizuya Saika
  • Organizer: First International Symposium on TGFβ and related signaling in Ocular Biology at Wakayama
  • Place of Presentation: 和歌山
  • Year and Date: 2015-03-28 – 2015-03-29
• [Presentation] マウス角膜創傷治癒過程での角膜血管新生におけるテネイシンX の役割 (2014)
  • Author(s): 住岡孝吉
  • Organizer: 第2 回 Mat r iCe l l フォーラム
  • Place of Presentation: 東京
  • Year and Date: 2014-09-06 – 2014-09-07
• [Presentation] Retrocorneal membraneと角膜内皮細胞 (2014)
  • Author(s): 住岡孝吉
  • Organizer: 第３回 関西角膜セミナー
  • Place of Presentation: 大阪
  • Year and Date: 2014-07-19
• [Presentation] Impaired angiogenic response in cornea by lacking tenascin X in mice (2014)
  • Author(s): Takayoshi Sumioka, Yuka Okada, Yuka Nidegawa, Masayasu Miyajima, Ken-ichi Matsumoto, Shizuya Saika
  • Organizer: ARVO2014
  • Place of Presentation: Orland, USA
  • Year and Date: 2014-05-04 – 2014-05-08
• [Presentation] 角膜創傷治癒過程での角膜血管新生におけるテネイシンXの役割 (2014)
  • Author(s): 住岡孝吉、岡田由香、二出川裕香、白井久美、宮嶋正康、雑賀司珠也
  • Organizer: 第118回日本眼科学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-04-02 – 2014-04-06
• [Presentation] Lacking tenascin X suppresses VEGF expression and neovascularization in an injured cornea in mice. (2014)
  • Author(s): Takayoshi Sumioka, Yuka Okada, Yuka Nidegawa, Masayasu Miyajima, Ken-ichi Matsumoto, Shizuya Saika
  • Organizer: KEYSTONE SYMPOSIA2014
  • Place of Presentation: Keystone resort, USA
• [Presentation] Impaired angiogenic response in cornea by lacking tenascin X in mice. (2013)
  • Author(s): Takayoshi Sumioka, Yuka Okada and Shizuya Saika
  • Organizer: Cornea Wakayama Symposium
  • Place of Presentation: 和歌山県
• [Presentation] Impaired Wound Healing In Corneal Stroma Of A Nitric Oxide Synthase Type II -deficient Mouse. (2013)
  • Author(s): Takayoshi Sumioka, Yuka Okada, Norihito Fujita, Masayasu Miyajima, Shizuya Saika.
  • Organizer: ARVO2013
  • Place of Presentation: seattle, USA
• [Presentation] マウス角膜実質創傷治癒過程におけるNitric Oxide 合成酵素 Type IIの役割. (2013)
  • Author(s): 住岡孝吉、岡田由香、藤田識人、宮嶋正康、雑賀司珠也
  • Organizer: 日本眼科学会総会
  • Place of Presentation: 東京
• [Presentation] 角膜上皮創傷治癒過程におけるTRPV1受容体の役割．
  • Author(s): 住岡孝吉、岡田由香、ピーター・ライナック、藤田識人、宮嶋正康、雑賀司珠也．
  • Organizer: 日本眼科学会総会
  • Place of Presentation: 東京
• [Presentation] Lacking TRPV1 ion channel receptor suppresses cytokines and substance P in an epithelium-debrided cornea in mice.
  • Author(s): T. Sumioka, Y. Okada, P.S. Reinach, N. Fujita, M. Miyajima, S. Saika．
  • Organizer: ARVO
  • Place of Presentation: Florida, USA
• [Presentation] 細胞外マトリックスによる炎症・組織線維化の制御.
  • Author(s): 住岡孝吉
  • Organizer: 第24回日本アレルギー学会春季臨床大会
  • Place of Presentation: 大阪
  • Invited