Quantifying Hyperglycemia-Associated Retinal Changes via Optical Coherence Tomography in Mice with Streptozotocin-Induced Diabetes

Abstract

Purpose: Streptozotocin (STZ)-induced diabetes in mice promotes changes in the retina similar to those in pre-diabetic retinopathy patients. While electroretinography (ERG) and histology have historically been used to evaluate hyperglycemia-induced retinal changes in mice, the application of optical coherence tomography (OCT) has not been adequately investigated. The purpose of this study is to determine if OCT can be used in vivo to noninvasively detect changes in retinal structure that correlate with the observed ERG and histological changes in diabetic mice.

Methods: Male, 12-week-old, C57Bl/6 mice received a once daily (QD) intraperitoneal injection of either 70 mg/kg STZ or vehicle for 5 days. Blood glucose was monitored to confirm sustained hyperglycemia (>250 mg/dl) in STZ-injected animals 1 week after the last injection. A subset of animals from each group were evaluated 2 and 4 weeks post-injection by OCT and ERG. Visual function was evaluated by ERG utilizing an intensity series of flashes ranging from -6.0 to 2.7 log scot cd s m^-2, as well as by OCT using 1.8 mm vertical and horizontal scans centered at the optic nerve for the purpose of quantifying inner retinal thickness.

Results: Mice receiving STZ or vehicle exhibited similar ocular function and structure as assessed by ERG and OCT 2 weeks post-injection. However, at 4 weeks post injection, STZ-injected mice displayed a reduction in b-wave amplitude compared to the vehicle group (-17%, p<0.0001). Furthermore, at 4 weeks post-injection, the STZ-injected animals showed a significant reduction in inner retinal thickness as measured by OCT (-4%, p<0.01).

Conclusions: These results demonstrate that OCT is a viable method for quantitatively assessing hyperglycemia-associated inner retinal thinning in mice. In addition, the significant thinning seen by OCT in the inner retina of STZ injected mice correlates well with a significant reduction in retinal function as demonstrated by the reduced ERG b-wave.

Keywords: 499 diabetic retinopathy • 552 imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • 691 retina: proximal (bipolar, amacrine, and ganglion cells)