Abstract
Purpose: :
We are using a mouse model of type 1 diabetes to evaluate the development and mechanism of retinal pigment epithelium (RPE) defects associated with this disease. Cellular changes in the outer retina occur at early stages of diabetes, well before vision loss or retinopathy can be identified clinically. The dc-ERG is a non-invasive measure of RPE function which can be applied to mouse models of diseases to assess the development of and mechanisms underlying visual changes. The dc-ERG waveform contains four slow components, the c-wave, fast oscillation, light peak and off response. Each component is generated by changes in ion conductance across the RPE apical or basal membranes, and can be affected by structural or physiological defects.
Methods: :
C57Bl/6J mice were injected with streptozotocin (STZ) to induce hyperglycemia and type 1 diabetes. Blood glucose was measured to verify efficacy of the drug. We used ERG-based techniques to measure the light-evoked components of the RPE (dc-ERG) and the neural retina (a-wave, b-wave). Structure of the outer retina and ion channel expression (GLUT1, Na+/K+ ATPase, CFTR) at each membrane was also evaluated.
Results: :
STZ-injected mice were hyperglycemic 1 week post-injection. Decreases in the c-wave, fast oscillation and off response of the dc-ERG were identified in STZ-injected mice between 1 and 2 weeks of hyperglycemia, and persisted through 8 weeks, when testing was concluded. In comparison, ERG a-waves were not altered at 2 weeks. At these early stages, no differences were noted in overall retinal structure or tight junctions between RPE cells of control or STZ mice.
Conclusions: :
RPE function is disrupted at an early stage in the STZ-induced mouse model of type 1 diabetes. These defects are not attributable to reductions in photoreceptor activity, and occur prior to breakdown of the outer blood retinal barrier.
Keywords: retinal pigment epithelium • diabetes • electroretinography: non-clinical