Effect of High Glucose Levels on Amyloid β Production in Retinas of Spontaneous Diabetes Mellitus Otsuka Long-Evans Tokushima Fatty Rats

The accumulation of amyloid beta(1-42) peptide (A beta(1-42)) 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 A(beta) in diabetic retinas. In addition, we investigated the relation between glucose level and A beta 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 A beta, was detected, and the expression levels of genes associated with A beta production (amyloid precursor protein, beta site APP cleaving enzyme, and presenilin) and A beta(1-42) 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 A beta production was enhanced by administration of glucose (3.0 g/kg; OGT test), and close relations between the retinal A beta(1-42) level and plasma blood glucose and HbA1c were observed. In conclusion, we have found that A beta accumulates easily in the retinas of LETO and OLETF rats due to the absence of NEP. In addition, we determined that the accumulation of A beta(1-42) 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 A beta in diabetic retinas.