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L. E. Johnson, M.-T. Perez, M. Larsen; Initial Increase of ERG Amplitudes in Type 2 Diabetes is Reversed by Normalization of Glycemia. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1891.
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To examine functional and physiological changes in the retina during the development of hyperglycemia in a rat model of type 2 diabetes and how glycemic control affects these parameters both acutely and long term.
Zucker diabetic fatty (ZDF) rats were compared with lean control rats using full field electroretinography (ERG) from 8 to 14 weeks of age as their fasted blood glucose levels increased to around 20 mM. ZDF rats were then either left untreated or given a long-acting insulin analog once daily from 17 weeks of age to reduce their glucose levels to <10 mM. ERGs were performed in all 3 groups until 22 weeks. The expression of glial fibrillary acidic protein (GFAP) and metallothioneins I and II (MT-I+II) was examined in retinas obtained at 23 weeks of age.
ZDF rats showed >10% higher scotopic a- and b-wave amplitudes (p<0.05 and p<0.05, respectively) from 12 weeks of age and about 10% delays in the implicit times of all oscillatory potential (OP) wavelets (p<0.01) from 14 weeks of age compared to lean counterparts. Administration of insulin normalized amplitudes within 3 hours, whereas the OP latencies were unchanged. Long term insulin treatment resulted in some normalization of OP latencies but a- and b-wave amplitudes became subnormal (p<0.05). GFAP overexpression was observed in hyperglycemic ZDF retinas in Müller glial cells whereas MT-I+II were mainly accumulated in the innermost retina. The level of expression of these proteins was normalized by insulin treatment.
The upregulation of GFAP and MT-I+II is likely to result from increased stress on the retina caused by high glucose levels. The development of hyperglycemia over time, however, also led to increasingly higher a- and b-wave amplitudes, indicative of the retina’s ability to adapt to chronic metabolic challenges. While insulin treatment caused some of the observed changes to reverse, lower than normal amplitudes were eventually observed. These contradictory results may be related to the paradoxical effect of normalization of blood glucose, which improves the long-term prognosis in diabetic retinopathy, but produces in some patients an initial worsening of retinopathy.
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