| First Author | Tarchick MJ | Year | 2016 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 57 |
| Issue | 7 | Pages | 3496-508 |
| PubMed ID | 27367517 | Mgi Jnum | J:257448 |
| Mgi Id | MGI:6115378 | Doi | 10.1167/iovs.15-18775 |
| Citation | Tarchick MJ, et al. (2016) Early Functional and Morphologic Abnormalities in the Diabetic Nyxnob Mouse Retina. Invest Ophthalmol Vis Sci 57(7):3496-508 |
| abstractText | PURPOSE: The electroretinogram c-wave is generated by the summation of the positive polarity hyperpolarization of the apical RPE membrane and a negative polarity slow PIII response of Muller glia cells. Therefore, the c-wave reduction noted in prior studies of mouse models of diabetes could reflect a reduction in the RPE component or an increase in slow PIII. The present study used a genetic approach to distinguish between these two alternatives. METHODS: Nyxnob mice lack the ERG b-wave, revealing the early phase of slow PIII. To visualize changes in slow PIII due to diabetes, Nyxnob mice were given streptozotocin (STZ) injections to induce diabetes or received vehicle as a control. After 1, 2, and 4 weeks of sustained hyperglycemia (>250 mg/dL), standard strobe flash ERG and dc-ERG testing were conducted. Histological analysis of the retina was performed. RESULTS: A reduced c-wave was noted at the 1 week time point, and persisted at later time points. In comparison, slow PIII amplitudes were unaffected after 1 week of hyperglycemia, but were significantly reduced in STZ mice at the 2-week time point. The decrease in amplitude occurred before any identifiable decrease to the a-wave. At the later time point, the a-wave became involved, although the slow PIII reductions were more pronounced. Morphological abnormalities in the RPE, including increased thickness and altered melanosome distribution, were identified in diabetic animals. CONCLUSIONS: Because the c-wave and slow PIII were both reduced, these results demonstrated that diabetes-induced reductions to the c-wave cannot be attributed to an early increase in the Muller glia-derived potassium conductance. Furthermore, because the a-wave, slow PIII and c-wave reductions were not equivalent, and varied in their onset, the reductions cannot reflect the same mechanism, such as a change in membrane resistance. The presence of small changes to RPE architecture indicate that the c-wave reductions present in diabetic mice likely represents a primary change in the RPE induced by hyperglycemia. |
