Retinal thickness changes in mice with type 2 diabetes mellitus quantified using an enhanced Iowa Reference Algorithm

Abstract

Purpose: Inner retinal thinning in humans and streptozotocin-induced (STZ) wild-type mice have been described. A mouse with leptin receptor mutation has diabetes until approximately 16 weeks of age (JAX B6.BKS(D)-Leprdb/J). In this study we compared retinal topography in vivo of B6.BKS(D)-Leprdb/J mice with supplemental STZ after 16 weeks using the Iowa Reference Algorithm for three-dimensional automated layer segmentation of spectral domain optical coherence tomography (OCT).

Methods: B6.BKS(D)-Leprdb/J mice (DM; n=18) and age-matched controls (C57BL/6; n=11) had retinal imaging (Bioptigen, Morrisville, NC) performed at the age of 10 weeks, 24 weeks, and 38 weeks. Glucose was monitored weekly and supplemental STZ was administered started at around 16 weeks to maintain hyperglycemia (glucose>300 mg/dL) once euglycemia set in. Using the Iowa Reference Algorithm, mathematically enhanced for mouse OCT, average change in thickness of the combined retinal nerve fiber layer and ganglion cell layer (RNFL-GCL) and total retinal thickness were quantified and compared using two-tailed paired t-test analysis for each group.

Results: The mean thickness of RNFL-GCL layer in DM at 10 weeks (8.9μm) was thinner (p=0.001) compared to the control group (10.8μm) and the mean total retinal thickness of the DM group at 10 weeks (209.3μm) was thinner (p=0.001) compared to the control group (214.4μm). The mean thickness of RNFL-GCL layer in DM at 24 weeks (8.4μm) was thinner (p=0.004) compared to the control group (9.9μm) and the mean total retinal thickness of the DM group at 10 weeks (220.4μm) was similar to the control group (218.7μm). The mean thickness of RNFL-GCL layer in DM at 38 weeks (7.0μm) was thinner (p=0.008) compared to control group (8.8μm) (95% CI). The mean total retinal thickness of the DM group at 38 weeks (216.7μm) was similar to the control group (216.2μm).

Conclusions: Attenuation of the inner retina (RNFL-GCL complex) is seen in a genetically modified type II diabetic mouse that continues with prolonged hyperglycemia maintained by exogenous STZ injections. These results suggest that neuroretinal thinning can be seen in genetic and exogenous animal models of diabetes.

Keywords: 499 diabetic retinopathy • 531 ganglion cells • 552 imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound)