Submission
| Title: | Unraveling Retinal Phenotypic Changes in a Hyperglycemic Late-Onset Alzheimer’s Disease Mouse Model |
| Presenter: | Surabhi Abhyankar |
| Institution: | Department of Biochemistry and Molecular Biology, Indiana University School of Medicine |
| Authors: | Abhyankar, Surabhi D.1,2, Luo, Qianyi2, Hartman, Gabriella D.2,3, Corson, Timothy W.1,2,3,4, Oblak, Adrian L.3,4, Lamb, Bruce T.3,4, Bhatwadekar, Ashay1,2,4
1 Indiana University, Department of Biochemistry and Molecular Biology, Indianapolis, Indiana; |
Abstract
| Background/Significance/Rationale: | At least 33 million people worldwide have Alzheimer’s disease (AD). Apolipoprotein E4 (APOE4) is a key predisposing gene variant in late-onset AD (LOAD) pathophysiology, the most common form of AD. Dementia and cognitive decline are more prevalent in people with diabetes. Diabetes and the APOE4 variant may interact to exacerbate retinal dysfunction and promote the onset and progression of diabetic retinopathy (DR). We examined visual impairment in APOE4-knock-in (LOAD-risk) and APOE3-KI (LOAD-neutral) mice, and whether the treatment with a western diet (WD) accelerates the development of DR phenotype. |
| Methods: | APOE4-KI and APOE3-KI mice were fed either WD or control diet (CD) for six-months. The effect of WD on body weight (BW) and fasting blood glucose was monitored. Retinal structure was assessed using optical coherence tomography (OCT) and fundus photography. Vasculature was visualized by fluorescein angiography (FA). Neural function of retinas was assessed using an electroretinogram (ERG). |
| Results/Findings: | Both WD-treated APOE4 and APOE3 mice exhibited increased BW and fasting blood glucose compared to CD-treated APOE4 and APOE3 mice. APOE4 mice showed evidence of reduction of retinal thickness by OCT, largest vein width, and vasculature by FA. APOE4 CD and WD-treated mice showed increased avascular area and arterial tortuosity compared to APOE3 mice. Retinal functional testing by ERG demonstrated significant reduction in a-wave and b-wave amplitudes for APOE4 CD and WD-treated mice. |
| Conclusions/Discussion: | APOE4 alleles are associated with retinal vascular dysfunction, functional deficits in the retinas, and increased susceptibility to retinal degeneration as compared to APOE3 alleles. Vascular changes and neural functional deficits are the earliest indicators of damage in the retina of LOAD-risk mice. |
| Translational/Human Health Impact: | These discoveries shed light on the mechanisms behind retinal dysfunction in a mouse model with a heightened risk of LOAD combined with diabetes and identify potential non-invasive novel biomarkers for AD for diagnosing and monitoring the disease progression. |
