Elucidation for the role of heparan sulfate in neural crest cell differentiation and establishment of a new concept for glaucoma pathogenesis.

• Project/Area Number: 19679008
• Research Category: Grant-in-Aid for Young Scientists (S)
• Allocation Type: Single-year Grants
• Research Field: Ophthalmology
• Research Institution: University of Fukui (2010-2011); Kumamoto University (2007-2009)
• Principal Investigator: INATANI Masaru 福井大学, 医学部, 教授 (40335245)
• Project Period (FY): 2007 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥114,530,000 (Direct Cost: ¥88,100,000、Indirect Cost: ¥26,430,000); Fiscal Year 2011: ¥23,920,000 (Direct Cost: ¥18,400,000、Indirect Cost: ¥5,520,000); Fiscal Year 2010: ¥23,920,000 (Direct Cost: ¥18,400,000、Indirect Cost: ¥5,520,000); Fiscal Year 2009: ¥23,920,000 (Direct Cost: ¥18,400,000、Indirect Cost: ¥5,520,000); Fiscal Year 2008: ¥24,700,000 (Direct Cost: ¥19,000,000、Indirect Cost: ¥5,700,000); Fiscal Year 2007: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
• Keywords: 眼科学 / ゲノム / 生理活性 / 糖鎖 / 発生・分化 / 臨床 / 緑内障 / ヘパラン硫酸 / 神経堤細胞

Research Abstract

The anomaly of the anterior chamber angle causes glaucoma. We elucidated the role of heparan sulfate in the anterior chamber angle development. The deficiency of heparan sulfate disturbs the differentiation of neural crest cells, which causes glaucoma in mice. We revealed that TGFβ_2 signaling in the differentiation of neural crest cells depends on the expression of heparan sulfate on the cell surface. We can inactivate fibroblasts by inhibiting the interaction between heparan sulfate and TGFβ_2, which improves the surgical outcome of filtration surgery in glaucoma animal models.

Research Products

• [Journal Article] The effect of Rho-associated protein kinase inhibitor on monkey Schlemm's canal endothelial cells (2012)
  • Author(s): Kameda T, Inoue T, Inatani M, 9人3番目
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 53 Issue: 6 Pages: 3092-3103
  • DOI: 10.1167/iovs.11-8018
  • Peer Reviewed
• [Journal Article] Impact of phacoemulsification on failure of trabeculectomy with mitomycin C (2012)
  • Author(s): Awai-Kasaoka N, Inoue T, Takihara Y, Kawaguchi A, Inatani M, 7人5番目
  • Journal Title: J Cataract Refract Surg Volume: 38 Issue: 3 Pages: 419-424
  • DOI: 10.1016/j.jcrs.2011.09.035
  • NAID: 120005148223
  • Peer Reviewed
• [Journal Article] Trabeculectomy with mitomycin C for open-angle glaucoma in phakic eyes vs pseudophakic eyes after phacoemulsification (2011)
  • Author(s): Takihara Y, Inatani M, 8人2番目
  • Journal Title: Arch Ophthalmol Volume: 129 Issue: 2 Pages: 152-157
  • DOI: 10.1001/archophthalmol.2010.348
  • Peer Reviewed
• [Journal Article] Success rates of trabeculotomy for steroid-induced glaucoma : a comparative, multicenter, retrospective, cohort study (2011)
  • Author(s): Iwao K, Inatani M, 17施設2番目
  • Journal Title: Am J Ophthalmol Volume: 151 Issue: 6 Pages: 1047-1056
  • DOI: 10.1016/j.ajo.2010.11.028
  • Peer Reviewed
• [Journal Article] Combined intravitreal bevacizumab and trabeculectomy with mitomycin C versus trabeculectomy with mitomycin C alone for neovascular glaucoma (2011)
  • Author(s): Takihara Y, Inatani M, 7人2番目
  • Journal Title: J Glaucoma Volume: 20 Issue: 3 Pages: 196-201
  • DOI: 10.1097/ijg.0b013e3181d9ce12
  • Peer Reviewed
• [Journal Article] Combined intravitreal bevacizumab and trabeculectomy with mitomycin Cversus trabeculectomy with mitomycin C alone for neovascular glaucoma (2011)
  • Author(s): Takihara Y
  • Journal Title: Journal of Glaucoma Volume: 20 Pages: 196-201
  • Peer Reviewed
• [Journal Article] Trabeculectomy with mitomycin C for open-angle glaucoma in phakic eyes pseudophakic eyes after phacoemulsification (2011)
  • Author(s): Takihara Y
  • Journal Title: Archives of Ophthalmology Volume: 129 Pages: 152-157
  • Peer Reviewed
• [Journal Article] Success rates of trabeculotomy for steroid-induced glaucoma : a comparative multicenter, retrospective, cohort study (2011)
  • Author(s): Iwao K
  • Journal Title: American Journal of Ophthalmology Volume: 151 Pages: 1047-1056
  • Peer Reviewed
• [Journal Article] Heparan sulfate regulates intraretinal axon pathfinding by retinal ganglion cells (2011)
  • Author(s): Ogata-Iwao M
  • Journal Title: Investigative Ophthalmology and Visual Science Volume: 52 Pages: 6671-6679
  • Peer Reviewed
• [Journal Article] Investigation of the association between SLC1A3 gene polymorphisms and normal tension glaucoma (2011)
  • Author(s): Yasumura R
  • Journal Title: Molecular Vision Volume: 17 Pages: 792-796
  • Peer Reviewed
• [Journal Article] Role of heparan sulfate in mammalian brain development current views based on the findings from Ext1 conditional knockout studies (2010)
  • Author(s): Yamaguchi Y, Inatani M, 5人2番目
  • Journal Title: Prog Mol Biol Trans Sci Volume: 93 Pages: 133-152
  • DOI: 10.1016/s1877-1173(10)93007-x
  • ISBN: 9780123812827
  • Peer Reviewed
• [Journal Article] Heparan sulfate deficiency in periocular mesenchyme causes microphthalmi and ciliary body dysgenesis (2010)
  • Author(s): Iwao K
  • Journal Title: Experimental Eye Research Volume: 90 Pages: 81-88
  • Peer Reviewed
• [Journal Article] Role of heparan sulfate in mammalian brain development current views based on the findings from Ext1 conditional knockout studies (2010)
  • Author(s): Yamaguchi Y
  • Journal Title: Progress in Molecular Biology and Translational Science Volume: 93 Pages: 133-152
  • Peer Reviewed
• [Journal Article] Genome-wide association study of normal tension glaucoma : common variants in SRBD1 and ELOVL5 contribute to disease susceptibility (2010)
  • Author(s): Writing Committee for the Normal Tension Glaucoma Genetic Study Group of Japan Glaucoma Society
  • Journal Title: Ophthalmology Volume: 117 Pages: 1331-1338
  • Peer Reviewed
• [Journal Article] Analysis of microsatellite polymorphisms within the GLC1F locus in Japanese patients with normal tension glaucoma (2010)
  • Author(s): Murakami K
  • Journal Title: Molecular Vision Volume: 16 Pages: 462-466
  • Peer Reviewed
• [Journal Article] Suppression of choroidal neovascularization by N-acetyl-cysteine in mice (2010)
  • Author(s): Hara R
  • Journal Title: Current Eye Research Volume: 35 Pages: 1012-1020
  • Peer Reviewed
• [Journal Article] Heparan sulfate deficiency in periocular mesenchyme causes microphthalmia and ciliary body dysgenesis (2010)
  • Author(s): Iwao K, Inatani M, et al.
  • Journal Title: Experimental Eye Research 90 Pages: 81-88
• [Journal Article] Heparan sulfate deficiency leads to Peters anomaly in mice by disturbing neural crest TGF-β_2 signaling (2009)
  • Author(s): Iwao K, Inatani M, 9人2番目
  • Journal Title: J Clin Invest Volume: 119 Pages: 1997-2008
  • DOI: 10.1172/jci38519
  • Peer Reviewed
• [Journal Article] Trabeculectomy with mitomycin C for neovascular glaucoma : Prognostic factors for surgical failure (2009)
  • Author(s): Takihara Y, Inatani M, 6人2番目
  • Journal Title: Am J Ophthalmol Volume: 147 Issue: 5 Pages: 912-918
  • DOI: 10.1016/j.ajo.2008.11.015
  • Peer Reviewed
• [Journal Article] Restricted post-trabeculectomy bleb formation by conjunctival scarring (2009)
  • Author(s): Iwao K, Inatani M, 5人2番目
  • Journal Title: Graefe Arch Clin Exp Ophthalmol Volume: 247 Issue: 8 Pages: 1095-1101
  • DOI: 10.1007/s00417-009-1051-4
  • Peer Reviewed
• [Journal Article] Heparan sulfate deficiency leads to Peters anomaly in mice by disturbing neural crest TGF-β_2 signaling (2009)
  • Author(s): Iwao K, Inatani M, et al.
  • Journal Title: Journal of Clinical Investigation 119 Pages: 1997-2008
• [Journal Article] Trabeculectomy with mitomycin C for neovascular glaucoma : Prognostic factors for surgical failure (2009)
  • Author(s): Takihara Y, Inatani M, et al.
  • Journal Title: American Journal of Ophthalmology 147 Pages: 912-918
• [Journal Article] Restricted post-trabeculectomy bleb formation by conjunctival scarring (2009)
  • Author(s): Iwao K, Inatani M, et al.
  • Journal Title: Graefe's Archive for Clinical and Experimental Ophthalmology 247 Pages: 1095-1101
• [Journal Article] Intraocular pressure elevation after injection of triamcinolone acetonide : A multicenter retrospective case-control study (2008)
  • Author(s): Inatani M, 15人1番目
  • Journal Title: Am J Ophthalmol Volume: 145 Issue: 4 Pages: 676-681
  • DOI: 10.1016/j.ajo.2007.12.010
  • Peer Reviewed
• [Journal Article] Intraocular pressure-lowering effects and safety of topical administration of a selective ROCK inhibitor, SNJ-1656, in normal volunteers (2008)
  • Author(s): Tanihara H, Inatani M, 7人2番目
  • Journal Title: Arch Ophthalmol Volume: 126 Issue: 3 Pages: 309-315
  • DOI: 10.1001/archophthalmol.2007.76
  • Peer Reviewed
• [Journal Article] Fate mapping of neural crest cells during eye development using a Protein 0 promoter-driven transgenic technique (2008)
  • Author(s): Iwao K, Inatani M, 4人2番目
  • Journal Title: Graefe Arch Clin Exp Ophthalmol Volume: 246 Issue: 8 Pages: 1117-1122
  • DOI: 10.1007/s00417-008-0845-0
  • Peer Reviewed
• [Journal Article] Intraocular pressure elevation after injection of triamcinolone acetonide : A multicenter retrospective case-control study (2008)
  • Author(s): Inatani M, Iwao K, et al.
  • Journal Title: American Journal of Ophthalmology 145 Pages: 676-681
• [Journal Article] Fate mapping of neural crest cells during eye development using a Protein 0 promoter-driven transgenic technique (2008)
  • Author(s): Iwao K, Inatani M, et al.
  • Journal Title: Graefe's Archive for Clinical and Experimental Ophthalmology 246 Pages: 1117-1122
• [Journal Article] Intraocular pressure-lowering effects and safety of topical administration of a selective ROCK inhibitor, SNJ-1656, in normal volunteers (2008)
  • Author(s): Tanihara H, Inatani M, et al.
  • Journal Title: Archives of Ophthalmology 126 Pages: 309-315
• [Journal Article] Fate mapping of neural crest cells during eye development using a Protein O promoter-driven transgenic technique. (2008)
  • Author(s): Iwao K
  • Journal Title: Graefe's Archive for Clinical and Experimental Ophthalmology 246 Pages: 1117-1122
  • Peer Reviewed
• [Journal Article] Netrin-1/DCC signaling in commissural axon guidance requires cell autonomous expression of heparan sulfate (2007)
  • Author(s): Matsumoto Y, Irie F, Inatani M, 5人3番目
  • Journal Title: J Neurosci Volume: 27 Issue: 16 Pages: 4342-4350
  • DOI: 10.1523/jneurosci.0700-07.2007
  • Peer Reviewed
• [Journal Article] Netrin-1/DCC signaling in commissural axon guidance requires cell autonomous expression of heparan sulfate (2007)
  • Author(s): Matsumoto Y, Irie F, Inatani M, et al.
  • Journal Title: Journal of Neuroscience 27 Pages: 4342-4350
• [Journal Article] Frequency and risk factors for intraocular pressure elevation after posterior sub-Tenon's capsule triamcinolone acetonide injection (2007)
  • Author(s): Iwao K, Inatani M, et al.
  • Journal Title: Journal of Glaucoma 16 Pages: 251-256
• [Journal Article] Effects of topical administration of Y-39983, a selective Rho-associated protein kinase inhibitor, on ocular tissues in rabbits and monkeys (2007)
  • Author(s): Tokushige H, Inatani M, et al.
  • Journal Title: Investigative Ophthalmology & Visual Science 48 Pages: 3216-3222
• [Journal Article] Frequency and risk factors for neovascular glaucoma after vitrectomy in eyes with proliferative diabetic retinopathy
  • Author(s): Goto A, Inatani M, 8人2番目
  • Journal Title: J Glaucoma Volume: (In press)
  • Peer Reviewed
• [Journal Article] Simultaneous increases in multiple proinflammatory cytokines in the aqueous humor of pseudophakic glaucomatous eyes
  • Author(s): Inoue T, Inatani M, 6人2番目
  • Journal Title: J Cataract Refract Surg Volume: (In press)
  • Peer Reviewed
• [Journal Article] Combined intravitreal bevacizumab and trabeculectomy with mitomycin C versus trabeculectomy with mitomycin C alone for neovascular glaucoma
  • Author(s): Takihara Y, Inatani M, et al.
  • Journal Title: Journal of Glaucoma (In press)
• [Journal Article] Trabeculectomy with mitomycin C for neovascular glaucoma : Prognostic factors for surgical failure.
  • Author(s): Takihara Y
  • Journal Title: American Journal of Ophthalmology (印刷中)
  • Peer Reviewed
• [Journal Article] Restricted post-trabeculectomy bleb formation by conjunctival scarring.
  • Author(s): Iwao K
  • Journal Title: Graefe's Archive for Clinical and Experimental Ophthalmology (印刷中)
  • Peer Reviewed
• [Journal Article] Fate mapping of neural crest cells during eye development using a Protein 0 promoter-driven transgenic technique.
  • Author(s): Iwao K, Inatani M, et. al.
  • Journal Title: Graefe's Archive for Clinical and Experimental Ophthalmology (印刷中)
  • Peer Reviewed
• [Presentation] Aqueous humor composition of glaucoma patients. Blood flow and aqueous flow in glaucoma (2011)
  • Author(s): Inatani M
  • Organizer: World Glaucoma Congress 2011
  • Place of Presentation: Paris, France
  • Year and Date: 2011-07-01
• [Presentation] Aqueous humor composition of glaucoma patients. Blood flow and aqueous flow in glaucoma (2011)
  • Author(s): Inatani M
  • Organizer: World Glaucoma Congress
  • Place of Presentation: フランス、パリ、コンベンションセンター(招待講演)
  • Year and Date: 2011-07-01
• [Presentation] Potential new drugs acting on the conventional out flow system (2010)
  • Author(s): Inatani M
  • Organizer: The 25^<th> APAO Congress-A Joint Meeting of APAO/AAO
  • Place of Presentation: Beijing, China
  • Year and Date: 2010-09-18
• [Presentation] The molecular mechanism of optic nerve head formation : The essential role of heparan sulfate proteoglycans (2010)
  • Author(s): Inatani M
  • Organizer: The 25^<th> APAO Congress-A Joint Meeting of APAO/AAO
  • Place of Presentation: Beijing, China
  • Year and Date: 2010-09-18
• [Presentation] Heparan sulfate deficiency leads to Peters anomaly in mice, disturbing TGF-s2 signaling in neural crest (2010)
  • Author(s): Inatani M
  • Organizer: The Annual Meeting of the Association for Research in Vision and Ophthalmology(ARVO), Fort Lauderdale
  • Place of Presentation: Florida, USA
  • Year and Date: 2010-05-05
• [Presentation] Heparan sulfate deficiency leads to Peters anomaly in mice, disturbing TGF-ss2 signaling in neural crest (2010)
  • Author(s): Inatani M
  • Organizer: The Annual Meeting of the Association for Research in Vision and Ophthalmology
  • Place of Presentation: 米国フロリダ州フォートローダデール、コンベンションセンター(招待講演)
  • Year and Date: 2010-05-05
• [Presentation] Heparan sulfate : the key regulator of optic nerve guidance (2009)
  • Author(s): Inatani M
  • Organizer: Nakajima Award Lecture APSEG-molecular pathology I APAO AAO Joint Congress
  • Place of Presentation: Bali, Indonesia
  • Year and Date: 2009-05-19
• [Presentation] 眼発生の分子メカニズムの探究と眼疾患モデルへの展開評議員会指名講演「眼疾患と動物モデル」 (2009)
  • Author(s): 稲谷大
  • Organizer: 第113回日本眼科学会総会
  • Place of Presentation: 東京都
  • Year and Date: 2009-04-18
• [Presentation] 眼発生の分子メカニズムの探究と眼疾患モデルへの展開 (2009)
  • Author(s): 稲谷大
  • Organizer: 「眼疾患と動物モデル」第113回日本眼科学会総会
  • Place of Presentation: 東京都
• [Presentation] Heparan sulfate : the key regulator of optic nerve guidance. Nakajima Award Lecture APSEG-molecular pathology I (2009)
  • Author(s): 稲谷大
  • Organizer: APAO AAO Joint Congress
  • Place of Presentation: インドネシア、バリ島、バリ国際会議場
• [Presentation] 眼発生の分子メカニズムの探究と眼疾患モデルへの展開評議員会指名講演「眼疾患と動物モデル」 (2009)
  • Author(s): 稲谷大
  • Organizer: 第113回日本眼科学会総会
  • Place of Presentation: 東京都、東京国際フォーラム
• [Presentation] Heparan sulfate regulates Smad signaling in anterior oculardevelopment. (2008)
  • Author(s): Iwao K
  • Organizer: The Annual Meeting of the Association for Research in Vision and Ophthalmology
  • Place of Presentation: Fort Lauderdale, Florida, USA
• [Presentation] 隅角の発生と発達緑内障 (2008)
  • Author(s): 稲谷 大
  • Organizer: 第12回眼科分子生物学研究会
  • Place of Presentation: 静岡県熱海市
• [Book] 生化学軸索ガイダンスにおけるヘパラン硫酸の役割 (2011)
  • Author(s): 稲谷大
  • Publisher: 日本生化学会
• [Book] 生化学 (2011)
  • Author(s): 稲谷大
  • Publisher: 日本生化学学会
• [Book] 日本眼科学会雑誌眼発生の分子メカニズムの探究と眼患モデルへの展開 (2010)
  • Author(s): 稲谷大
  • Publisher: 日本眼科学会
• [Book] 臨床眼科眼疾患の臨床と動物モデル (2010)
  • Author(s): 稲谷大
  • Publisher: 医学書院
• [Book] 臨床眼科 (2010)
  • Author(s): 稲谷大
  • Publisher: 医学書院
• [Book] あたらしい眼科 緑内障セミナー 2. 血管新生緑内障と濾過手術 (2009)
  • Author(s): 稲谷大
  • Total Pages: 2
  • Publisher: メディカル葵出版
• [Book] 実験医学中枢神経発生におけるヘパラン硫酸の役割 (2007)
  • Author(s): 稲谷大, 他
  • Publisher: 羊土社
• [Book] あたらしい眼科緑内障セミナー 2. 血管新生緑内障と濾過手術
  • Author(s): 稲谷 大
  • Publisher: メディカル葵出版(印刷中)
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