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Elucidation and Treatment of Retinal Involvement in Spontaneously-Diabetic Rats

Research Project

Project/Area Number10671637
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionKanazawa University

Principal Investigator

SHIRAO Yutaka  Faculty of Medicine, Kanazawa University Associate Professor, 医学部, 助教授 (50154365)

Co-Investigator(Kenkyū-buntansha) TAKAHIRA Masayuki  University Hospital, Kanazawa University Assistant, 医学部・附属病院, 助手 (70283108)
NISHIMURA Akira  University Hospital, Kanazawa University Assistant, 医学部・附属病院, 助手 (70272979)
SEGAWA Yasunori  University Hospital, Kanazawa University Lecturer, 医学部・附属病院, 講師 (00262569)
SAKURAI Mayumi  Faculty of Medicine, Kanazawa University Assistant, 医学部, 助手 (50303269)
HIGASHIDE Tomomi  University Hospital, Kanazawa University Assistant, 医学部・附属病院, 助手 (20291370)
Project Period (FY) 1998 – 1999
Project Status Completed(Fiscal Year 1999)
Budget Amount *help
¥3,200,000 (Direct Cost : ¥3,200,000)
Fiscal Year 1999 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1998 : ¥2,400,000 (Direct Cost : ¥2,400,000)
Keywordsretina / choroid / nitric oxide / dopamine / oscillatory potential / hypoxia / streptozotocin / OLETF / 自然発症糖尿病ラット / ストレプトゾトシン誘発糖尿病ラット / 網膜電図 / 一酸化窒素合成酵素 / 眼底血流 / 糖尿病 / 食餌制限 / OLETF / ドーパミン
Research Abstract

The oscillatory potentials (Ops) of the electroretinogram were delayed in streptozotocin (STZ)-induced diabetic rats as long as they were hyperglycemic and were restored to normal as long as they became normoglycemic by a subsequent insulin treatment, which chronologically coincided with a decrease and an increase in the retinal blood flow but not with the degree of retinal vascular leakage. The Ops of excised rabbit eye cups were very sensitively delayed to minute hypoxia. In control rats, nitric oxide synthase (NOS) inhibitors, non-selective or neuronal NOS-selective, similarly decreased the choroidal blood flow. Inducible NOS was hardly detected in the rat choroid. Total NOS activity in the retinal pigment epithelium (RPE)-choroid decreased in STZ-induced diabetic rats, while that in the neural retina was not. Neuronal NOS was supposedly responsible for the abovementioned decrease in the NOS activity. These results suggest that the OP delay in diabetes is underlain by hypoperfusion- … More hypoxia in both the neural retina and the choroid.
The intra-neural retinal contents of dopamine and its metabolites were significantly lower in STZ-induced diabetic rats, while that of other putative intra-retinal neurotransmitters such as gamma-amino butylic acid, aspartic acid, glutamic acid and taurine was not. The intra-neural retinal content of dopamine was chronologically correlated to the OP amplitude but not to the degree of OP delay. Our previous study had revealed dopamine enhances the OP amplitude but has no effect on the OP time course. These results suggest that the delay and the attenuation of the Ops in diabetes may derive from separate mechanisms.
Genetically-programmed spontaneously diabetic rats (OLETF rats) on ad-libitum feeding (hyperglycemic) had larger OP than the non-diabetes-programmed rats of the same strain (normoglycemic) and smaller OP than the OLETF rats on diet (normoglycemic). This result can be interpreted as the OLETF rats on ad-libitum feeding showed larger-than-normal Ops because of their inherited defect of cholecystokinnin-A receptor and the OLETF rats on diet gained further OP amplitude by the amount of hyperglycemia-dependent decrease. The OLETF rats on ad-libitum feeding showed delayed Ops compared with the OLETF rats on diet. The intra-neural retinal content of dopamine and the activity of the rate-limiting enzyme for dopamine synthesis were significantly lower in the OLETF rats on ad-libitum feeding, while intra-neural retina content of other putative intra-retinal neurotransmitters such as gamma-amino butylic acid, aspartic acid, glutamic acid and taurine was not. The OLETF rats on ad-libitum feeding had significantly higher levels of vascular endothelial growth factor and advanced glycation end-product.
Hyperglycemia supposedly decreases the blood flow in both the neural retina and the choroid, which may manifest as the OP delay ; and diminishes the neural retinal dopamine metabolism, which may manifest as the OP attenuation. The mechanism responsible for the OP delay is reversible as long as hyperglycemia persists within the order of weeks. Less

Report

(3results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report

Research Products

(16results)

All Other

All Publications

  • [Publications] Yutaka Shirao and Kazuo Kawasaki: "Electrical Responses from Diabetic Retina"Progress in Retinal and Eye Research. 17 (1). 59-76 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yasunori Segawa, Yutaka Shirao, Tomomi Higashide,他6名: "Upregulation of Retinal Vascular Endothelial Growth Factor mRNAs in Spontaneously Diabetic Rats without Ophthalmoscopic Retinopathy"Ophthalmic Research. 30 (6). 333-339 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 河崎一夫、白尾 裕、瀬川安則、他21名: "視覚における情報処理機構 第102回日本眼科学会総会 宿題報告 律動様小波が関与する網膜内情報処理とその異常 ―糖尿病網膜症を中心に―"日本眼科学会雑誌. 102(12). 813-836 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 山田陽久、瀬川安則、浅井宏志、他6名: "食餌制限がOLETFラットの網膜電図に与える効果"OLETFラット研究会記録集. 4. 134-137 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yutaka Shirao, Yasunori Segawa, Tomomi Higashide,他8名: "Biochemical and electrophysiological alterations in the OLETF rat retina"Obesity and NIDDM : Lessons from the OLETF Rat. 129-139 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yutaka Shirao and Kazuo Kawasaki: "Electrical Responses from Diabetic Retina."Progress in Retinal and Eye Research. 17(1). 59-76 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yasunori Segawa, Yutaka Shirao, Tomomi Higashide et al 16: "Upregulation of Retinal Vascular Endothelial Growth Factor mRNAs in Spontaneously Diabetic Rats without Ophthalmoscopic Retinopathy."Ophthalmic Research. 30(6). 333-339 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kazuo Kawasaki, Yutaka Shirao, Yasunori Segawa, et al 21: "Preretinopathic Changes in the Oscillatory Potential in Diabetic Retina Interpretation and Significance."Journal of Japanese Ophthalmological Society. 102(12). 813-836 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Akihisa Yamada, Yasunori Segawa, Hiroshi Asai, et al 6: "Effects of caloric restriction on the electroretinogram of OLETF rats."Proceedings of Annual Meeting for OLETF rat Researches. 4. 134-137 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yutaka Shirao, Yasunori Segawa, Tomomi Higashide et al 8: "Biochemical and electrophysiological alterations in the OLETF rat retina."Obesity and NIDDM : Lessons from the OLETF Rat. 129-139 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yutaka Shirao, Yasunori Segawa, Tomomi Higashide, 他8名: "Biochemical and electrophysiological altertions in the OLETF rat retina."Obesity and NIDDM : Lessons from the OLETF Rat. 129-139 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yutaka Shirao and Kazuo Kawasaki: "Electrical Responses from Diabetic Retina" Progress in Retinal and Eye Research. 17(1). 59-76 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Sakai,E.Shirasawa,Y.Shirao and K.Kawasaki: "Restoration of Oscillatory Potentials by Insulin Treatment in Streptozotocin-Induced Diabetic Rats" Association for Research in Vision and Ophthalmology 1998 Annual Meeting Fort Lauderdale, Florida May 10-15.

    • Related Report
      1998 Annual Research Report
  • [Publications] Yasunori Segawa,Yutaka Shirao,Tomomi Higashide,他16名: "Upregulatin of Retinal Vascular Endothelial Growth Factor mRNAs in Spontaneously Diabetic Rats without Ophthalmoscopic Retinopathy" Ophthalmic Research. 30(6). 333-339 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 河崎一夫,白尾 裕,瀬川安則,他21名: "視覚における情報処理機構 第102回 日本眼科学会総会 宿題報告 律動様小波が関与する網膜内情報処理とその異常-糖尿病網膜症を中心に-" 日本眼科学会雑誌. 102(12). 813-836 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 山田陽久,瀬川安則,浅井宏志,他6名: "食餌制限がOLETFラットの網膜電図に与える効果" OLETFラット研究会記録集. 4. 134-137 (1998)

    • Related Report
      1998 Annual Research Report

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Published : 1998-04-01   Modified : 2016-04-21  

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