In Vivo Evaluation of Retinal and Choroidal Structure in a Mouse Model of Long-Lasting Diabetes. Effect of Topical Treatment with Citicoline.

Abstract

Purpose: To in vivo investigate, in a mouse model of type 1 diabetes, the effect of long-lasting hyperglycemia on retinal and choroidal structures and to verify the protective effect of topical treatment with citicoline.

Methods: 40 wild-type C57B6 mice (6-8 weeks old) were used in this study. Diabetes was induced by two consecutive intraperitoneal injections of streptozotocin. 5 animals were considered as buffered saline-treated controls, 15 animals as buffered saline-treated diabetic mice, 5 animals as citicoline-treated controls and 15 animals as citicoline-treated diabetic mice. Eight months after the induction of diabetes in vivo analysis of the retina was performed using the Spectralis HRA (Heidelberg Retinal Angiography) + Optical Coherence Tomography (OCT), an instrument that allows to obtain simultaneously both OCT scans and fluorescein angiography (FA) images.

Results: Our study shows that neuroretinal abnormalities, in particular a significant narrowing of Retinal Nuclear Fiber Layer (19.3±2.2 vs 23.2±2.4, µm±SD, p=0.01), Ganglion Cells Complex (73.9±4.8 vs 83.8±3.4, p=0.003) Inner Retinal Layer (93.4±3.4 vs 103.5±4.8, p=0.0007) and Retinal thickness (223.8±3.9 vs 236.7±5.8, p=0.0004) can be detected in vivo in a mouse model of long-standing type 1 diabetes by OCT and demonstrates, for the first time in the mouse, a significant reduction of choroidal thickness (67.3±3.3 vs 84.7±1.9, p=0.0001). In line with the hypothesis that neuroprotection might help preventing diabetic retinopathy, neuroretinal, but not choroidal (choroid lacks a neuronal component) dysfunctions were prevented by chronic treatment with topical citicoline.

Conclusions: Altogether these findings demonstrate that diabetes-driven neuroretinal dysfunctions can be monitored in vivo by OCT in the mouse. Retinal neuroprotection as obtained by topical citicoline protects from these abnormalities suggesting this approach as a possible way to prevent diabetic retinopathy.

Keywords: 499 diabetic retinopathy • 615 neuroprotection • 552 imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound)