Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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Effect of High Glucose Levels on Amyloid β Production in Retinas of Spontaneous Diabetes Mellitus Otsuka Long-Evans Tokushima Fatty Rats
Noriaki NagaiYoshimasa ItoTadatoshi Tanino
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2015 Volume 38 Issue 4 Pages 601-610

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Abstract

The accumulation of amyloid β1–42 peptide (Aβ1–42) in retina is implicated in the development of retinal ganglion cell apoptosis and diabetic retinopathy. In this study we demonstrate that spontaneous diabetes mellitus Otsuka Long-Evans Tokushima Fatty (OLETF) rats can be used as an animal model in studies to identify the expression of Aβ in diabetic retinas. In addition, we investigated the relation between glucose level and Aβ production in the retinas of OLETF rats. In the retinas of Long-Evans Tokushima Otsuka (LETO) rats used as normal controls and OLETF rats, no expression of neprilysin (NEP), which degrades Aβ, was detected, and the expression levels of genes associated with Aβ production (amyloid precursor protein, β site APP cleaving enzyme, and presenilin) and Aβ1–42 levels in the retinas of 60-week-old OLETF rats with diabetes mellitus were significantly higher than in 60-week-old LETO rat retinas. Furthermore, the increase in the expression levels of genes associated with Aβ production was enhanced by administration of glucose (3.0 g/kg; OGT test), and close relations between the retinal Aβ1–42 level and plasma blood glucose and HbA1c were observed. In conclusion, we have found that Aβ accumulates easily in the retinas of LETO and OLETF rats due to the absence of NEP. In addition, we determined that the accumulation of Aβ1–42 in the retinas of OLETF rats is promoted by high plasma glucose levels. Therefore OLETF rats may be a suitable model for studies to identify the expression of Aβ in diabetic retinas.

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© 2015 The Pharmaceutical Society of Japan
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