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(Investigative Ophthalmology and Visual Science. 2004;45:4592-4600.)
© 2004 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.04-0842
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Paired-Flash Identification of Rod and Cone Dysfunction in the Diabetic Rat

Joanna A. Phipps,1,2 Erica L. Fletcher,2 and Algis J. Vingrys1

1From the Department of Optometry and Vision Sciences, University of Melbourne, Carlton, Australia; and the 2Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Australia.

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 HBA1c (>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.




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