Mechanisms underlying phosphorylation of alpha-crystallin in diabetic retinopathy

• Project/Area Number: 15K10856
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Hokkaido University
• Principal Investigator: Kase Satoru 北海道大学, 大学病院, 講師 (60374394)
• Co-Investigator(Kenkyū-buntansha): 神田 敦宏 北海道大学, 医学研究院, 特任講師 (80342707)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: αークリスタリン / VEGF / 糖尿病網膜症 / αBークリスタリン / 病理組織学 / リン酸化 / 血管新生

Outline of Final Research Achievements

We found that retinal pigment epithelium (RPE)/choroid thickness was significantly increased from 4 to 8 weeks after streptozotocin (STZ) stimulation, which reached maximum at 8 weeks. Histopathology demonstrated thickened choroid comprising stromal accumulation of some materials and pigments as well as small vessels 8 weeks after stimulation. We further examined protein concentrations using ELISA system. VEGF and alphaB-crystallin concentrations in RPE/choroid proteins were significantly lower in 8 weeks after STZ mice than 4 weeks or control mice. Retinal tissue proteins also revealed similar VEGF/alphaB-crystallin concentrations. We now try to analyze mechanisms underlying such down-regulation of VEGF/alphaB-crystallin in STZ-induced diabetic mice.

Research Products

• [Journal Article] Usefulness of Flow Cytometry in Diagnosis of IgG4-Related Ophthalmic Disease and Extranodal Marginal Zone B-Cell Lymphoma of the Ocular Adnexa (2017)
  • Author(s): Kase S, Ishijima K, Uraki T, Suimon Y, Suzuki Y, Kase M, Ishida S.
  • Journal Title: Anticancer Res Volume: 37 Issue: 9 Pages: 5001-5004
  • DOI: 10.21873/anticanres.11913
  • Peer Reviewed
• [Journal Article] Effect of topical rebamipide on goblet cells in the lid wiper of human conjunctiva (2017)
  • Author(s): Kase S、Shinohara T、Kase M、Ishida S
  • Journal Title: Exp Ther Med Volume: 13 Issue: 6 Pages: 3516-3522
  • DOI: 10.3892/etm.2017.4390
  • Peer Reviewed
• [Journal Article] Vascular anomaly in the levator aponeurosis of neurofibromatosis type 1 (2017)
  • Author(s): 3.Kase S, Shinohara T, Noda M, Ishida S, Kase M
  • Journal Title: Int J Ophthalmol Volume: 10 Issue: 4 Pages: 656-657
  • DOI: 10.18240/ijo.2017.04.25
  • Peer Reviewed
• [Journal Article] Long-term follow-up of conjunctival melanoma treated with topical interferon alpha-2b eye drops as adjunctive therapy following surgical resection (2017)
  • Author(s): Kikuchi I、Kase S、Ishijima K、Ishida S
  • Journal Title: Graefes Arch Clin Exp Ophthalmol Volume: 255 Issue: 11 Pages: 2271-2276
  • DOI: 10.1007/s00417-017-3754-2
  • Peer Reviewed
• [Journal Article] Cytopathologic findings of cell block materials from the vitreous: Diagnostic distinction between intraocular lymphoma and non-lymphomatous diseases (2017)
  • Author(s): Kanno-Okada H, Takakuwa E, Tagawa Y, Kase S, Hatanaka KC, Hatanaka Y, Namba K, Mitsuhashi T, Matsuno Y.
  • Journal Title: Pathol Int Volume: 67 Issue: 7 Pages: 342-349
  • DOI: 10.1111/pin.12551
  • NAID: 120006484244
  • Peer Reviewed
• [Journal Article] 睫毛乱生に対するラジオ波メス睫毛根焼灼の治療効果 (2017)
  • Author(s): 浦木健彦、加瀬 諭、木下哲志、石嶋 漢、石田 晋
  • Journal Title: 眼科手術 Volume: 30 Pages: 187-190
  • Peer Reviewed
• [Journal Article] 瞼板内角質嚢胞との鑑別を要した 眼瞼結膜嚢胞性病変の1 例 (2017)
  • Author(s): 水門由佳、加瀬 諭、石嶋 漢、高桑恵美、石田 晋
  • Journal Title: 日本眼腫瘍学会誌 Volume: 6 Pages: 1-4
  • Peer Reviewed
• [Journal Article] 翼状片に対する新たな無切除Z型切開回転術の手術成績 (2017)
  • Author(s): 堤 雅幸、堀江幸弘、加瀬 諭、 北市伸義
  • Journal Title: 臨床眼科 Volume: 71 Pages: 789-794
  • Peer Reviewed
• [Journal Article] Clinical and histological evaluation of large macular holes surgery using the inverted ILM flap technique. (2016)
  • Author(s): Kase S, Saito W, Mori S, Saito M, Ando R, Dong Z, Suzuki T, Noda K, Ishida S.
  • Journal Title: Clin Ophthalmol Volume: 9 Pages: 11-14
  • DOI: 10.2147/opth.s119762
  • Peer Reviewed / Open Access
• [Journal Article] Coincidence of inflamed conjunctival carcinoma in situ and primary pterygium. (2016)
  • Author(s): Endo H, Kase S, Suzuki Y, Kase M.
  • Journal Title: Case Rep Ophthalmol Volume: 7 Issue: 3 Pages: 208-212
  • DOI: 10.1159/000450824
  • Peer Reviewed / Open Access
• [Journal Article] Serial frequencies and clinical features of uveitis in Hokkaido, Japan. (2016)
  • Author(s): Iwata D, Mizuuchi K, Aoki K, Horie Y, Kase S, Namba K, Ohno S, Ishida S, Kitaichi N.
  • Journal Title: Ocul Immunol Inflamm. Volume: 20 Issue: sup1 Pages: 1-4
  • DOI: 10.1080/09273948.2016.1184286
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of vascular endothelial growth factor-C by tumor necrosis factor-α in the conjunctiva and pterygium. (2016)
  • Author(s): Dong Y, Kase S, Dong Z, Fukuhara J, Tagawa Y, Ishizuka ET, Murata M, Shinmei Y, Ohguchi T, Kanda A, Noda K, Ishida S.
  • Journal Title: Int J Mol Med Volume: 38 Pages: 545-550
  • Peer Reviewed / Open Access
• [Journal Article] Diagnostic efficacy of cell block method for vitreoretinal lymphoma. (2016)
  • Author(s): Kase S, Namba K, Iwata D, Mizuuchi K, Kitaichi N, Tagawa Y, Okada-Kanno H, Matsuno Y, Ishida S
  • Journal Title: Diagn Pathol Volume: 11 Issue: 1 Pages: 29-29
  • DOI: 10.1186/s13000-016-0479-1
  • NAID: 120005753722
  • Peer Reviewed / Open Access
• [Journal Article] Phosphorylation of alphaB-crystallin in epiretinal membrane of human proliferative diabetic retinopathy. (2016)
  • Author(s): Dong Y, Dong Z, Kase S, Ando R, Fukuhara J, Kinoshita S, Inafuku S, Tagawa Y, Ishizuka ET, Saito W, Murata M, Kanda A, Noda K, Ishida S
  • Journal Title: Int J Ophthalmol Volume: 9 Pages: 1100-1105
  • DOI: 10.18240/ijo.2016.08.03
  • Peer Reviewed / Open Access
• [Journal Article] Choroidal thickness in diabetic retinopathy in relation to long-term systemic treatments for diabetes mellitus. (2016)
  • Author(s): Kase S, Endo H, Yokoi M, Kotani M, Katsuta S, Takahashi T, Kase M.
  • Journal Title: Eur J Ophthalmol Volume: 26 Issue: 2 Pages: 158-162
  • DOI: 10.5301/ejo.5000676
  • Peer Reviewed / Open Access
• [Journal Article] Inhibition of DNA methylation and Methyl-CpG-binding protein 2 suppresses RPE transdifferentiation: relevance to proliferative vitreoretinopathy (2015)
  • Author(s): He S, Barron E, Khanamiri HN, Spee C, Zhou P, Kase S, Wang Z, Dustin LD, Hinton DR
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 56 Pages: 5579-5589
• [Journal Article] 硝子体浸潤を伴った脈絡膜悪性黒色腫の1例 (2015)
  • Author(s): 横山英恵, 加瀬 諭，鈴木康夫，勝田 聡，高橋光生，篠原敏也，石田 晋，加瀬 学
  • Journal Title: 臨床眼科 Volume: 69 Pages: 1545-1550
• [Presentation] Immunocytochemical analysis with cell block method in vitreous infusion fluids of patients with vitreoretinal lymphoma (2017)
  • Author(s): Kase S, Namba K, Okada H, Iwata D, Mizuuchi K, Tagawa Y, Kitaichi N, Ishida S.
  • Organizer: 14th Congress of the International Ocular Inflammation Society (IOIS)
  • Int'l Joint Research
• [Presentation] Clinical features of malignant eyelid tumors in Hokkaido University Hospital in Japan (2017)
  • Author(s): Ishijima K, Kase S, Noda M, Nozaki M, Ishida S.
  • Organizer: International Society of Oral Oncology (ISOO)
  • Int'l Joint Research
• [Presentation] Usefulness of flow cytometry in diagnosis of extranodal marginal zone B-cell lymphoma of the ocular adnexa (2017)
  • Author(s): Kase S, Ishijima K, Uraki T, Suzuki Y, Ishida S
  • Organizer: International Society of Oral Oncology (ISOO)
  • Int'l Joint Research
• [Presentation] Rhegmatogenous retinal detachment in a patient with choroidal melanoma simulating choroidal detachment (2017)
  • Author(s): Kase S, Suimon Y, Ishijima K, Ishida S
  • Organizer: International Society of Oral Oncology (ISOO)
  • Int'l Joint Research
• [Presentation] A clinicopathological study on IgG4-related ophthalmic disease (2017)
  • Author(s): Suimon Y, Kase S, Ishijima K, Ishida S
  • Organizer: International Society of Oral Oncology (ISOO)
  • Int'l Joint Research
• [Presentation] Visco-assisted internal limiting membrane translocation technique for unclosed macular hole (2017)
  • Author(s): 1.Saito M, Noda K, Shibata Y, Fujiya A, Suzuki T, Ando R, Mori S, Kase S, Ishida S
  • Organizer: Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting
  • Int'l Joint Research
• [Presentation] Usefulness of flow cytometry in diagnosis of extranodal marginal zone B-cell lymphoma of the ocular adnexa (2017)
  • Author(s): Kase S, Ishijima K, Uraki T, Suzuki Y, Ishida S
  • Organizer: International Society of Ocular Oncology (ISOO) Biennial Conference
  • Int'l Joint Research
• [Presentation] Rhegmatogenous retinal detachment in a patient with choroidal melanoma simulating choroidal detachment (2017)
  • Author(s): Kase S, Suimon Y, Ishijima K, Ishida S
  • Organizer: International Society of Ocular Oncology (ISOO) Biennial Conference
  • Int'l Joint Research
• [Presentation] A clinicopathological study on IgG4-related ophthalmic diseas (2017)
  • Author(s): Suimon Y, Kase S, Ishijima K, Ishida S
  • Organizer: International Society of Ocular Oncology (ISOO) Biennial Conference
  • Int'l Joint Research
• [Presentation] Role of vitrectomy as an initial treatment for globe rupture due to blunt trauma (2017)
  • Author(s): Kase S
  • Organizer: 18th Joint Event on European Ophthalmology Congress & Ocular Pharmacology
  • Invited
• [Presentation] Inflammatory pathogensis of choroidal thickenss alteration in diabetic retinopathy. Workshop on Diabetic Retinopathy (2017)
  • Author(s): Kase S
  • Organizer: Global Ocular Inflammation Workshops (GOIW)
  • Invited
• [Presentation] 糖尿病眼における熱ショック蛋白α-クリスタリンと最終糖化産物の発現 (2017)
  • Author(s): 加瀬 諭、石田 晋
  • Organizer: 第23回日本糖尿病眼学会
• [Presentation] 光線力学療法を施行した脈絡膜血管腫の循環動態 (2017)
  • Author(s): 加瀬 諭、橋本勇希、野田航介、石田 晋
  • Organizer: 第34回日本眼循環学会
• [Presentation] 眼付属器MALTリンパ腫の診断におけるフローサイトメトリの有用性 (2017)
  • Author(s): 加瀬 諭、石嶋 漢、浦木健彦、鈴木康夫、石田 晋
  • Organizer: 第5回日本眼形成再建外科学会学術集会
• [Presentation] 術後療法としてインターフェロンα-2b点眼治療を行った結膜上皮内癌・扁平上皮癌の4例 (2017)
  • Author(s): 加瀬 諭、石嶋 漢、石田 晋
  • Organizer: 第5回日本眼形成再建外科学会学術集会
• [Presentation] 眼瞼に発生した内分泌性ムチン生成汗腺癌の1例 (2017)
  • Author(s): 加瀬 諭、石嶋 漢、畑中佳奈子、桑原 健、石田 晋
  • Organizer: 第28回日本眼瞼義眼床手術学会
• [Presentation] Choroidal thickness in diabetic retinopathy in relation to long-term systemic treatments for diabetic mellitus (2017)
  • Author(s): 加瀬 諭
  • Organizer: 第23回日本糖尿病眼学会総会
  • Invited
• [Presentation] 眼内腫瘍の最新画像診断学とOCTAとLSFG. シンポジウム「眼内腫瘍の最新画像診断学」 (2017)
  • Author(s): 加瀬 諭
  • Organizer: 第71回日本臨床眼科学会
  • Invited
• [Presentation] 眼部腫瘍の診断と治療 (2017)
  • Author(s): 加瀬 諭
  • Organizer: 第11回四国 Eye ランドセミナー
  • Invited
• [Presentation] VEGFタンパク質の分解系. シンポジウム「後眼部疾患の新しい創薬ターゲット 私のイチ押し！」 (2017)
  • Author(s): 加瀬 諭
  • Organizer: 第121回日本眼科学会総会
  • Invited
• [Presentation] 糖尿病治療歴と糖尿病網膜症における脈絡膜厚変化 (2017)
  • Author(s): 加瀬 諭
  • Organizer: 第5 回 眼と 全身疾患セミナー in 札幌
  • Invited
• [Presentation] 眼内悪性リンパ腫の診断における眼病理学の役割 (2017)
  • Author(s): 加瀬 諭
  • Organizer: 第17 回 網膜ラウンジ
  • Invited
• [Presentation] 内眼手術の苦痛 (2017)
  • Author(s): 加瀬 諭
  • Organizer: あやめ池眼科懇談会
  • Invited
• [Presentation] レバミピド点眼液投与後に発症した急性涙嚢炎における病理組織学的検討 (2015)
  • Author(s): 石嶋 漢、加瀬 諭、畑中佳奈子、石田 晋
  • Organizer: 第3回日本眼形成再建外科学会学術集会
  • Place of Presentation: 岡山国際交流センター（岡山県岡山市）
  • Year and Date: 2015-12-12
• [Presentation] PDTトリプル療法を行ったポリープ状脈絡膜血管症における治療1年後視力の規定因子 (2015)
  • Author(s): 安藤 亮、齋藤 航、廣岡季里子、鈴木智浩、吉澤史子、齋藤理幸、加瀬 諭、森 祥平、野田航介、石田 晋
  • Organizer: 第54回日本網膜硝子体学会総会、第32回日本眼循環学会合同学会
  • Place of Presentation: ベルサール渋谷ガーデン（東京都渋谷区）
  • Year and Date: 2015-12-04
• [Presentation] ベバシズマブ硝子体内注射が奏功した血管増殖性網膜腫瘍の3例 (2015)
  • Author(s): 川向 友子、齋藤 航、加瀬 諭、石田 晋
  • Organizer: 第54回日本網膜硝子体学会総会、第32回日本眼循環学会合同学会
  • Place of Presentation: ベルサール渋谷ガーデン（東京都渋谷区）
  • Year and Date: 2015-12-04
• [Presentation] アフリベルセプト併用PDTトリプル療法1年後の治療成績 (2015)
  • Author(s): 鈴木智浩、齋藤 航、森 祥平、齋藤理幸、安藤 亮、加瀬 諭、廣岡季里子、吉澤史子、野田航介、石田 晋
  • Organizer: 第54回日本網膜硝子体学会総会、第32回日本眼循環学会合同学会
  • Place of Presentation: ベルサール渋谷ガーデン（東京都渋谷区）
  • Year and Date: 2015-12-04
• [Presentation] Clinicopathological study on epiretinal membrane of ocular sarcoidosis (2015)
  • Author(s): Kase S, Namba K, Mizuuchi K, Iwata D, Kitaichi N, Ohno S, Ishida S
  • Organizer: AAO (American Academy of Ophthalmology)2015
  • Place of Presentation: Sands Expo（Las Vegas,USA）
  • Year and Date: 2015-11-14
  • Int'l Joint Research
• [Presentation] 黄斑円孔に対するinverted ILM flap techniqueの硝子体手術成績と臨床病理学的検討 (2015)
  • Author(s): 加瀬 諭、齋藤 航、森 祥平、齋藤理幸、董 震宇、安藤 亮、鈴木智浩、野田航介、石田 晋
  • Organizer: 第69回日本臨床眼科学会
  • Place of Presentation: ANAクラウンプラザホテルグランコート名古屋（愛知県名古屋市）
  • Year and Date: 2015-10-22
• [Presentation] 高血圧性脈絡膜症の脈絡膜厚と脈絡膜循環の経時的変化 (2015)
  • Author(s): 齋藤理幸、齋藤 航、橋本勇希、廣岡季里子、加瀬 諭、森 祥平、安藤 亮、野田航介、石田 晋
  • Organizer: 第69回日本臨床眼科学会
  • Place of Presentation: ANAクラウンプラザホテルグランコート名古屋（愛知県名古屋市）
  • Year and Date: 2015-10-22
• [Presentation] 急性帯状潜在性網膜外層症における脈絡膜層別厚と脈絡膜循環動態の関連 (2015)
  • Author(s): 橋本勇希、齋藤 航、齋藤理幸、金泉沙宝、森 祥平、安藤 亮、加瀬 諭、野田航介、石田 晋.
  • Organizer: 第69回日本臨床眼科学会
  • Place of Presentation: ANAクラウンプラザホテルグランコート名古屋（愛知県名古屋市）
  • Year and Date: 2015-10-22
• [Presentation] Diagnostic efficacy of cell block method for vitreoretinal lymphoma (2015)
  • Author(s): Kase S, Namba K, Iwata D, Mizuuchi K, Ishida S.
  • Organizer: 13th IOIS (International Ocular Inflammation Society)
  • Place of Presentation: Hilton San Francisco Union Square（San Francisco, USA）
  • Year and Date: 2015-09-25
  • Int'l Joint Research
• [Presentation] 眼内悪性リンパ腫の診断におけるセルブロック（細胞塊）標本の有用性 (2015)
  • Author(s): 加瀬 諭、南場研一、水内一臣、岩田大樹、北市伸義、石田 晋
  • Organizer: フォーサム2015
  • Place of Presentation: グランフロント大阪（大阪府大阪市）
  • Year and Date: 2015-07-10
• [Presentation] 結膜節外辺縁帯B細胞性リンパ腫におけるレニン・アンジオテンシン系の病態への関与 (2015)
  • Author(s): 石塚タンエルダル、神田敦宏、加瀬 諭、安藤 亮、董 陽子、稲福沙織、田川義晃、野田航介、石田 晋
  • Organizer: 第119回日本眼科学会総会
  • Place of Presentation: ロイトン札幌（北海道札幌市）
  • Year and Date: 2015-04-16
• [Book] 硝子体灌流液を用いたセルブロック法 (2017)
  • Author(s): 加瀬 諭
  • Publisher: 眼科手術
• [Book] 翼状片の手術適応～どのような症例が手術の適応となるのか？～．角結膜．眼科 眼科手術の適応. 最新情報 (2017)
  • Author(s): 加瀬 諭
  • Publisher: 眼科
• [Book] 眼瞼・結膜セミナー24．結膜メラノーシスと悪性黒色腫 (2017)
  • Author(s): 加瀬 諭
  • Publisher: あたらしい眼科
• [Book] IX腫瘍 ７ 脈絡膜血管腫（限局性） (2017)
  • Author(s): 加瀬 諭
  • Publisher: 眼底疾患パーフェクトアトラス
• [Book] IX腫瘍 ８ 脈絡膜骨腫 (2017)
  • Author(s): 加瀬 諭
  • Publisher: 眼底疾患パーフェクトアトラス
• [Book] 結膜腫瘍の臨床病理. 特集 臨床に直結する眼病理 (2017)
  • Author(s): 福原淳一、加瀬 諭
  • Publisher: Monthly Book OCULISTA
• [Book] 眼科臨床エキスパート (2015)
  • Author(s): 石嶋 漢、加瀬 諭
  • Total Pages: 476
  • Publisher: 医学書院
• [Book] 日本臨床 (2015)
  • Author(s): 加瀬 諭
  • Publisher: 日本臨床社
• [Book] あたらしい眼科 (2015)
  • Author(s): 加瀬 諭、石田 晋
  • Total Pages: 1129
  • Publisher: メディカル葵出版
• [Book] 眼科臨床エキスパート (2015)
  • Author(s): 加瀬 諭
  • Total Pages: 476
  • Publisher: 医学書院