Effect of PACAP on adult retinal stem cell and the regenerative potential.

• Project/Area Number: 21592246
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Showa University
• Principal Investigator: SEKI Tamotsu 昭和大学, 医学部, 兼任講師 (10245855)
• Co-Investigator(Kenkyū-buntansha): NAKAMACHI Tomoya 昭和大学, 遺伝子組換え実験室, 助教 (30433840)
• Co-Investigator(Renkei-kenkyūsha): SHIODA Seiji 昭和大学, 医学部, 教授 (80102375)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 眼組織学 / 緑内障 / PACAP / 網膜保護 / 網膜神経幹細胞 / 網膜神経変性 / マウス

Research Abstract

Retinal neuroprotective effect of PACAP was evaluated in transient ischemia model induced by high intraocular pressure. PACAP suppressed retinal ganglion cells(RGCs) with bimodal fashion with cAMP and MAPK pathways. Retinal protective effect of endogenous PACAP was examined using heterozygous PACAP KO mice with NMDA model. heterozygous PACAP KO mice showed high number of RGCs and less number of TUNEL positive cells in NMDA-treated retina. These data suggest that exogenous and endogenous PACAP have a neuroprotective potential in retinal RGCs. Furthermore, number of BrdU positive cells peaked on day 3 after NMDA treatment, and about 90% of BrdU positive cells were overlapped with microglia/macrophage marker. PACAP administration increased the number of BrdU positive cells after NMDA-treatment. Increment of the number of BrdU positive cells may be involved in neuroprotective effect of PACAP.

Research Products

• [Journal Article] Suppression of rat retinal ganglion cell death by PACAP following transient ischemia induced by high intraocular pressure (2011)
  • Author(s): Seki T, Itoh H, Nakamachi T, Endo K, Wada Y, Nakamura K, Shioda S
  • Journal Title: J Mol Neurosci Volume: 43(1) Pages: 30-34
• [Journal Article] Neuroprotective effect of PACAP against NMDA-induced retinal damage in the mouse (2011)
  • Author(s): Endo K, Nakamachi T, Seki T, Kagami N, Wada Y, Nakamura K, Kishimoto K, Hori M, Tsuchikawa D, Shinntani N, Hashimoto H, Baba A, Koide R, Shioda S
  • Journal Title: J Mol Neurosci Volume: 43(1) Pages: 22-29
• [Journal Article] Suppression of rat retinal ganglion cell death by PACAP following transient ischemia induced by high intraocular pressure. (2011)
  • Author(s): Seki T, Itoh H, Nakamachi T, Endo K, Wada Y, Nakamura K, Shioda S
  • Journal Title: J Mol Neurosci Volume: 43(1) Pages: 30-34
  • Peer Reviewed
• [Journal Article] Neuroprotective effect of PACAP against NMDA-induced retinal damage in the mouse. (2011)
  • Author(s): Endo K, Nakamachi T, Seki T, Kagami N, Wada Y, Nakamura K, Kishimoto K, Hori M, Tsuchikawa D, Shinntani N, Hashimoto H, Baba A, Koide R, Shioda S
  • Journal Title: J Mol Neurosci Volume: 43(1) Pages: 22-29
  • Peer Reviewed
• [Presentation] PACAP誘導性の涙液分泌におけるアクアポリン5の役割 (2012)
  • Author(s): 中町智哉、会沢洋一、大滝博和、養父佐知子、関保、和田悦洋、荒田悟、新谷紀人、橋本均、馬場明道、塩田清二
  • Organizer: 第117回日本解剖学会総会・全国学術集会
  • Place of Presentation: 甲府
• [Presentation] The retinoprotective effect of exogenous PACAP involves a modulation of retinal microglia/macrophage (2011)
  • Author(s): Wada Y, Nakamachi T, Endo K, Seki T, Ohtaki H, Tsuchikawa D, Hori M, Farkas J, Tsuchida M, Yoshikawa A, Kagami N, Imai N, Shioda S
  • Organizer: The 10th international Symposium on VIP, PACAP and Related Peptides
  • Place of Presentation: Eilat, Israel
  • Year and Date: 2011-12-15
• [Presentation] PACAP stimulates the lacrimation via aquaporin 5 translocatoin in mouse (2011)
  • Author(s): Nakamachi T, Aizawa Y, Ohtaki H, Seki T, Wada Y, Kagami N, Arata S, Hashimoto H, Shintani N, Baba A, Farkas J, Reglodi D, Shioda S
  • Organizer: The 10th international Symposium on VIP, PACAP and Related Peptides
  • Place of Presentation: Eilat, Israel
  • Year and Date: 2011-12-14
• [Presentation] The exogenous PACAP is possible modulater of the activation of retinal microglia/macrophage in the injury retina (2011)
  • Author(s): Wada Y, Nakamachi T, Endo K, Seki T, Ohtaki H, Tsuchikawa D, Hori M, Farkas J, Tsuchida M, Yoshikawa A, Kagami N, Imai N, Shioda S
  • Organizer: Symposium of the 20th Annual Meeting of The Israel Society for Neuroscience "Basic and Clinical Research of GPCRs"
  • Place of Presentation: Eilat, Israel
  • Year and Date: 2011-12-13
• [Presentation] Effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on reactive astrocyte induced by brain damage in mice (2011)
  • Author(s): Nakamachi T, Nakamura K, Wada Y, Kagami N, Tsuchikawa D, Hori M, Imai N, Yoshikawa A, Seki T, Atrata S, Shioda S
  • Organizer: 41st Annual meeting Society for Neuroscience
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2011-11-15
• [Presentation] PACAP STIMULATES THE LACRIMATION VIA AQUAPORIN 5 TRANSLOCATOIN IN MOUSE (2011)
  • Author(s): Nakamachi T, Aizawa Y, Ohtaki H, Seki T, Wada Y, Kagami N, Arata S, Hashimoto H, Shintani N, Baba A, Farkas J, Reglodi D and Shioda S
  • Organizer: The 10th international Symposium on VIP, PACAP and Related Peptides
  • Place of Presentation: Eilat, Israel
• [Presentation] Effect of pituitary adenylate cyclase-activating polypeptide(PACAP) on reactive astrocyte induced by brain damage in mice (2011)
  • Author(s): Tomoya Nakamachi, Keisuke Nakamura, Yoshihiro Wada, Nobuyuki Kagami, Daisuke Tsuchikawa, Motohide Hori, Nori Imai, Akira Yoshikawa, Tamotsu Seki, Satoru Arata, and Seiji Shioda
  • Organizer: The 41th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Washington, DC
• [Presentation] PACAPによる涙液分泌促進作用機序の解析 (2011)
  • Author(s): 中町智哉・会沢洋一・大滝博和・関保・和田悦洋・加賀美信幸・荒田悟・塩田清二
  • Organizer: 第36回日本比較内分泌学会
  • Place of Presentation: 東京
• [Presentation] 涙液分泌機能低下を示すPACAP欠損マウスを用いた涙液分泌機構の解析 (2011)
  • Author(s): 中町智哉、会沢洋一、大滝博和、関保、和田悦洋、加賀美信幸、荒田悟、塩田清二
  • Organizer: 第58回日本実験動物学会
  • Place of Presentation: 東京
• [Presentation] Investigation Of Neuroprotective Effects Of PACAP Against NMDA-induced Retinal Damage in Mice. ARVO (2011)
  • Author(s): Seki T, Nakamachi T, Endo K, Shioda S
  • Organizer: The Association for Research in Vision and Ophthalmology
  • Place of Presentation: Fortlauderdale, Fl.
• [Presentation] 新規ドライアイ疾患モデル動物としてのPACAP遺伝子欠損マウスの評価 (2011)
  • Author(s): 中町智哉、会沢洋一、大滝博和、関保、遠藤貴美、荒田悟、新谷紀人、橋本均、馬場明道、塩田清二
  • Organizer: 第57回日本実験動物学会
  • Place of Presentation: 京都
• [Presentation] Investigation Of Neuroprotective Effects Of PACAP Against NMDA-induced Retinal Damage in Mice (2011)
  • Author(s): Seki T, Nakamachi T, Endo K, Shioda S
  • Organizer: ARVO (The Association for Research in Vision and Ophthalmology)
  • Place of Presentation: Fortlauderdale, Fl
• [Presentation] Retinal Protective Effect of Pituitary Adenylate Cyclase-activating Polypeptide(PACAP)Against NMDA-induced Damage in Mice (2010)
  • Author(s): Tomoya Nakamachi, Kimi Endo, Tamotsu Seki, Nobuyuki Kagami, Keisuke Nakamura, Yoshihiro Wada Kouji Kishimoto, Jozsef Farkas, Satoru Arata, Seiji Shioda
  • Organizer: 5th International Peptide Symposium
  • Place of Presentation: 京都
  • Year and Date: 2010-12-05
• [Presentation] Neuroprotective Effect of PACAP(Pituitary Adenylate Cyclase-Activating Polypeptide)against NMDA-induced retinal damage in mice (2010)
  • Author(s): K.Endo, T.Nakamachi, T.Seki, N.Kagami, K.Nakamura, Y.Wada, K.Kishimoto, Y.Ichohashi, S.Shioda
  • Organizer: GPCR2010
  • Place of Presentation: 京都ガーデンパレスホテル
  • Year and Date: 2010-03-30
• [Presentation] NMDA誘導性網膜障害マウスに対するPACAPの保護効果 (2010)
  • Author(s): 遠藤貴美, 中町智哉, 関保, 加賀美信幸, 中村圭輔, 市橋陽子, 塩田清二
  • Organizer: 第115回 日本解剖学会総会・全国学術大会
  • Place of Presentation: 岩手県民会館
  • Year and Date: 2010-03-29
• [Presentation] Retinal Protective Effect of Pituitary Adenylate Cyclase-activating Polypeptide(PACAP) Against NMDA-induced Damage in Mice (2010)
  • Author(s): Nakamachi T, Endo K, Seki T, Kagami N, Nakamura K, Wada Y, Kishimoto K, Farkas J, Arata S, Shioda S
  • Organizer: 5th International Peptide Symposium
  • Place of Presentation: Kyoto
• [Presentation] Neuroprotective effect of PACAP(Pituitary adenylate cyclase-activating polypeptide) against NMDA-induced retinal damage in mice (2010)
  • Author(s): Endo K, Nakamachi T, Seki T, Kagami N, Nakamura K, Wada Y, Kishimoto K, Ichihashi Y, Shioda S
  • Organizer: Official satellite symposium of the 14th International Congress of Endocrinology(ICE2010)(GPCR2010)
  • Place of Presentation: Kyoto
• [Presentation] PACAP遺伝子欠損マウスにおける涙液分泌機能異常 (2010)
  • Author(s): 中町智哉・会沢洋一・大滝博和・養父佐知子・関保、遠藤貴美、荒田悟、新谷紀人、橋本均、馬場明道、塩田清二
  • Organizer: 第115回日本解剖学会総会・全国学術集会
  • Place of Presentation: 盛岡
• [Presentation] NMDA誘導性網膜障害マウスに対するPACAPの保護効果 (2010)
  • Author(s): 遠藤貴美・中町智哉・関保・加賀美信幸・中村圭輔・市橋陽子・塩田清二
  • Organizer: 第115回日本解剖学会総会・全国学術集会
  • Place of Presentation: 盛岡
• [Presentation] Effects of Pituitary Adenylate Cyclase-Activating Polypeptide(PACAP)on the Survival of Ganglion Cells in the Rat Retina after Intraocular Hypertension (2009)
  • Author(s): H.Itoh, T.Seki, T.Nakamachi, K.Endo, S.Shioda
  • Organizer: Yakushima2009(Satelite Symposium on The 9th international Symposium on VIP, PACAP and Related Peptides)
  • Place of Presentation: Kagoshima, Japan
  • Year and Date: 2009-10-07
• [Presentation] EFFECT OF PACAP ON TEAR SECRETION IN MOUSE (2009)
  • Author(s): T.Nakamachi, Y.Aizawa, H.Ohtaki, S.Yotu, T.Seki, K.Endo, K.Nakamura, K.Nobuyuki, S.Arata, N.Shintani, H.Hashimoto, A.Baba, S.Shioda
  • Organizer: The 9th international Symposium on VIP, PACAP and Related Peptides
  • Place of Presentation: Kagoshima, Japan
  • Year and Date: 2009-10-07
• [Presentation] Effects of pituitary adenylate cyclase-activating polypeptide(PACAP) on the survival of ganglion cells in the rat retina after intraocular hypertension (2009)
  • Author(s): Itoh H, Seki T, Nakamachi T, Endo K, Shioda S
  • Organizer: Yakushima 2009(Satellite Symposium of the 9th International Symposium on VIP, PACAP and Related Peptides) Phylogenetic Aspects of Neuropeptides-from Invertebrates to Humans
  • Place of Presentation: Yakushima, Kagoshima
• [Presentation] Effect of PACAP on tear secretion in mouse (2009)
  • Author(s): Nakamachi T, Aizawa Y, Ohtaki H, Yofu S, Seki T, Endo K, Nakamura K, Kagami N, Arata S, Shintani N, Hashimoto H, Baba A, Shioda S
  • Organizer: The 9th International Symposium on VIP, PACAP and Related Peptides
  • Place of Presentation: Kagoshima
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