Lamina-specific anatomical and functional imaging of normal and diabetic rat retina

H. Cheng, D. E. Olson, Y. Liu, P. M. Thule, M. T. Pardue, T. Q. Duong Yerkes Imaging Center, Emory University, Atlanta, GA, United States, School of medicine, Emory University, Atlanta, GA, United States, Atlanta VA Medical Center, Atlanta, GA, United States, Department of Ophthalmology, Emory University, Atlanta, GA, United States Introduction Diabetic retinopathy (DR) is a leading cause of blindness. In its late stages DR is primarily a vascular disease, but neural dysfunction may contribute at earlier stages [1]. Current diagnosis of DR relies on confirmation of vascular extravasation, thrombosis, or hemorrhage, and no clinically significant method has been devised to identify DR patients before established vasculopathy. Streptozotocin (STZ) induced diabetes is an established rat model of DR. While nine to twelve months of hyperglycemia are usually required to observe typical vasculopathic DR derangements, abnormal tissue oxygenation in the retina has been reported as early as 3.5 months after STZ injection using phosphorescence [2] and the ∆pO2 technique [3]. Histologic changes in retinal thickness occur within 7.5 months [4]. Although powerful, existing techniques have significant limitations. In addition to the lack of laminar specificity the phosphorescence technique cannot distinguish between oxygen arriving from retinal and choroidal vasculature and is applicable only for large vessels. The ∆pO2 technique measures vitreous humor oxygenation near, but not in, the retina and layer-specific attribution is impossible. Non-invasive MRI has the potential to provide the unique advantages of anatomical, physiological (blood flow and tissue oxygenation) and functional information in a single setting without regard to tissue depth or limitation of light path. However, until recently, MRI has demonstrated generally inferior spatial and/or temporal resolution relative to many optical techniques. Our lab has recently developed MRI techniques to image the retina at very high spatial resolution with layer specificity. Using anatomical MRI we have resolved three retinal tissue “layers” in cat and rat retinas [3].The addition of Gd-DTPA contrast-enhanced MRI further resolved two vascular layers. BOLD fMRI of the retina associated with visual stimuli and physiological challenges in the cat [5] and rat retina [6] was also recently reported. The goal of this study was to apply these lamina-specific MRI and fMRI techniques to evaluate early signs of DR in rat retina. We hypothesized that MRI can be used to resolve lamina-specific structural and functional changes associated with diabetic retinopathy. As a first step, we quantified the thickness of different retinal layers and investigated the BOLD fMRI responses to hyperoxia and hypercapnia in diabetic (DM) and non-diabetic control (Con) rats.