Abstract
Purpose:
The Ins2(Akita) mouse is a model of diabetes and heterozygous for a mutation in the insulin 2 gene resulting in beta-cell dysfunction, hypoinsulinemia, and hyperglycemia. The purpose of this study was to assess global and local inner and outer retinal thickness alterations in Ins2(Akita) diabetic mice by automated segmentation of spectral domain optical coherence tomography (SD-OCT) images.
Methods:
SD-OCT imaging was performed in Ins2(Akita) diabetic mice (n = 5) and wild type mice (n = 5) at 12 weeks of age using a commercially available instrument (Spectralis; Heidelberg). In each mouse, 31 raster B-scans were acquired over a 30 x 25 degree retinal area nasal to the optic disk. Using an automated software algorithm developed in Matlab, 5 retinal cell layer interfaces were detected: 1) vitreous/internal limiting membrane; 2) inner nuclear/outer plexiform; 3) outer nuclear/inner segment ellipsoid (ISe); 4) outer segment/retinal pigment epithelium (RPE); and 5) RPE/choroid. Based on automated segmentation, total retinal thickness (TRT), outer retinal thickness (ORT), inner retinal thickness (IRT), and photoreceptor outer segment length (OSL) were mapped. Mean and standard deviation (SD) of thickness measurements were compared using unpaired t-test. The percentage of retinal area with thickness above or below the normal confidence interval established in wild type mice was calculated for each retinal layer. Statistical significance was accepted at p < 0.05.
Results:
Blood glucose levels in Ins2(Akita) diabetic mice (397 ± 109 mg/dL, n = 5) were significantly elevated compared to measurements in wild type mice (156 ± 23 mg/dL, n = 5) (p = 0.001), confirming the presence of diabetes. Automated segmentation of 4 retinal cell layers was successfully performed in both diabetic and wild type mice. There was no statistically significant difference in mean TRT (p = 0.67), IRT (p = 0.15), ORT (p = 0.52), OSL (p = 0.09) or the SDs of any retinal cell layer (p > 0.09). On average, less than 9% of the retinal area in diabetic mice had decreased TRT, IRT, ORT, or OSL and less than 8% had increased TRT, IRT, or ORT. However, on average, 17% of the retinal area in diabetic mice had increased OSL.
Conclusions:
Alterations in inner and outer retinal thickness maps were not observed in Ins2(Akita) mice, indicating minimal global and local retinal structural changes at 12 weeks of age.