Diabetic retinopathy (DR) is a leading cause of blindness in the US and one of the major complications of both Type 1 and Type 2 diabetes. Although DR is widely accepted to be an ischemia-driven disease, the current diagnosis and grading of DR severity is based solely on anatomic alterations such as the quantification of abnormal retinal microvasculature in non-proliferative disease or angiogenesis in proliferative stages. As a result, retinal impairment is irreversible in most DR patients when diagnosed, largely due to the lack of technology to quantify retinal ischemia and the lack of knowledge of the underlying mechanism of retinal ischemia. This proposal aims to investigate retinal ischemia in early diabetes using a novel optical coherence tomography technology, which offers the capability to quantify metabolic rate of oxygen (MRO2) in the retina for the first time. We refer to this new technology as visible-light optical coherence tomography or vis-OCT. We seek to identify when MRO2 alterations initially occur, the causes of MRO2 alterations, and whether intervention of MRO2 affects the development of DR in a unique Type 1 mouse model. At the end of the project period, we will have 1) established a time line and mechanistic knowledge of retinal MRO2 changes during the development and progression of DR and 2) fully-optimized the vis-OCT system that is ready to be translated for the next-stage patient testing.
Significant improvement in clinical management of diabetic retinopathy will be possible if it's earliest pathological alterations can be detected and thoroughly understood. Quantitative imaging of retinal oxygen metabolism and comprehensive investigation of pathophysiology of dysfunctional retinal oxygen supply/consumption may provide such a possibility. This project seeks to apply novel, clinically-translatable, functional imaging technology and combine it with longitudinal animal model studies to address these needs.
|Lewis, Sarah Aileen; Takimoto, Tetsuya; Mehrvar, Shima et al. (2018) The effect of Tmem135 overexpression on the mouse heart. PLoS One 13:e0201986|
|Farnoodian, Mitra; Sorenson, Christine M; Sheibani, Nader (2018) Negative Regulators of Angiogenesis, Ocular Vascular Homeostasis, and Pathogenesis and Treatment of Exudative AMD. J Ophthalmic Vis Res 13:470-486|
|Aboualizadeh, Ebrahim; Sorenson, Christine M; Schofield, Alex J et al. (2018) Temporal diabetes-induced biochemical changes in distinctive layers of mouse retina. Sci Rep 8:1096|
|Saghiri, Mohammad Ali; Asatourian, Armen; Nguyen, Eric H et al. (2018) Hydrogel Arrays and Choroidal Neovascularization Models for Evaluation of Angiogenic Activity of Vital Pulp Therapy Biomaterials. J Endod 44:773-779|
|Melgar-Asensio, Ignacio; Kandela, Irawati; Aird, Fraser et al. (2018) Extended Intravitreal Rabbit Eye Residence of Nanoparticles Conjugated With Cationic Arginine Peptides for Intraocular Drug Delivery: In Vivo Imaging. Invest Ophthalmol Vis Sci 59:4071-4081|
|Gurel, Zafer; Sheibani, Nader (2018) O-Linked ?-N-acetylglucosamine (O-GlcNAc) modification: a new pathway to decode pathogenesis of diabetic retinopathy. Clin Sci (Lond) 132:185-198|
|Saghiri, Mohammad Ali; Asatourian, Armen; Sheibani, Nader (2018) Angiogenesis and the prevention of alveolar osteitis: a review study. J Korean Assoc Oral Maxillofac Surg 44:93-102|
|Farnoodian, Mitra; Sorenson, Christine M; Sheibani, Nader (2018) PEDF expression affects the oxidative and inflammatory state of choroidal endothelial cells. Am J Physiol Cell Physiol 314:C456-C472|
|Urban, Ben Ewell; Xiao, Lei; Chen, Siyu et al. (2018) In Vivo Superresolution Imaging of Neuronal Structure in the Mouse Brain. IEEE Trans Biomed Eng 65:232-238|
|Zaitoun, Ismail S; Cikla, Ulas; Zafer, Dila et al. (2018) Attenuation of Retinal Vascular Development in Neonatal Mice Subjected to Hypoxic-Ischemic Encephalopathy. Sci Rep 8:9166|
Showing the most recent 10 out of 33 publications