1999 Fiscal Year Final Research Report Summary
Elucidation and Treatment of Retinal Involvement in Spontaneously-Diabetic Rats
| Project/Area Number |
10671637
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Ophthalmology
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| Research Institution | Kanazawa University |
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Principal Investigator |
SHIRAO Yutaka Faculty of Medicine, Kanazawa University Associate Professor, 医学部, 助教授 (50154365)
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| 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)
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| Project Period (FY) |
1998 – 1999
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| Keywords | retina / choroid / nitric oxide / dopamine / oscillatory potential / hypoxia / streptozotocin / OLETF |
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| 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-
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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
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Research Products
(10 results)
