Paired-flash identification of rod and cone dysfunction in the diabetic rat.

Purpose: To investigate the onset of retinal neural dysfunction in the streptozotocin (STZ)-induced diatebic rat.

Methods: A cohort of 20 Sprague-Dawley rats were randomly assigned to treatment (STZ 50 mg/kg, n = 10) and control (citrate buffer, n = 10) groups and observed for 12 weeks. Diabetes was confirmed by blood glucose (>15 mmol/L) and HBA(1c) (>7.0%). Treated animals received 2 to 3 U insulin daily. Retinal function was monitored using paired-flash electroretinograms (ERGs) at baseline and various time points between 2 days and 12 weeks after treatment, to allow isolation of rod and cone components. Protocols compared photoreceptor and inner retinal responses (rod and cone) at each time point.

Results: Losses in the function of rod photoreceptors and the inner retina were seen 2 days after STZ injection, with recovery in some components by 4 weeks and a secondary loss of function at 12 weeks. Some inner retinal responses (cone response and rod oscillatory potentials (OPs) remained consistently depressed over the entire 12 weeks.

Conclusions: Retinal neural dysfunction was observed as early as 2 days after STZ injection. These acute changes reflect either STZ toxicity or hyperglycemia as a result of pancreatic compromise. Consistent loss over the 12 weeks of the cone response and OPs suggests a vulnerability of the inner retina to STZ-related effects. The 12-week losses in function of retinal neurons are consistent with a generalized diabetic neuropathy, since impaired function developed simultaneously in both inner and outer retinal neurons.