Abstract
Abstract: :
Purpose: The aim of this study was to examine the electrophysiology of retinal neurons in the streptozotocin (STZ) rat model of diabetes over a twelve-week period post diabetogenesis. Methods: Twenty Sprague-Dawley rats were assigned to groups of control and treated (n=10) animals (single injection of STZ (50 mg/kg)). Diabetes was confirmed by hyperglycemia (blood sugar >15 mmol) and HbA1c (12.66%±0.44). Treated rats were injected with 2U insulin daily. Electroretinograms (ERG) were collected (250 msec epochs; 0.3-3000 Hz filters; 2 kHz acquisition) on anaesthetised rats at three luminous energy levels (1.3-2.1 log cd-s.m-2) and rod and cone contributions were isolated using single or twin-flash paradigms. Signals were collected after 24 hrs of dark adaptation at baseline (prior to) and at 2 days, 1, 4, 6 and 12 weeks following STZ injection. Rod PIII waveforms were modeled using the characteristics of the phototransduction cascade and the post-receptoral components (PII) extracted by digital subtraction of the PIII from the raw waveform or filtering (oscillatory potentials (OPs) 55-280 Hz) of the conditioned waveform. Results: A transient reduction (30%) in the rod PIII amplitude was evident 2 days following injection. This was sustained for 2 weeks and recovered at 4 weeks post-injection. A permanent 44% decrease in the PIII developed after 12 weeks of diabetes compared with baseline (p<0.01). Significant losses in the rod post-receptoral waveforms (PII, 41% p<0.05: OPs, 27% p<0.01) were also present at this time. The cone PII was significantly reduced (19.8%, p<0.05) in STZ animals at 12 weeks but the small cone signals frustrated PIII extraction. Conclusions: We find that the STZ rat shows a dysfunction in both rod and cone responses. We propose that the early loss (2 weeks) reflects the direct effect of STZ on retinal elements whereas the latter effects (12 weeks) result from diabetes induced metabolic dysfunction in retinal neurons. Our data indicates that the photoreceptoral dysfunction might mediate the inner retinal changes.
Keywords: diabetes • electroretinography: non-clinical • retina: distal(photoreceptors, horizontal cell