In vivo retinal imaging is associated with cognitive decline, blood-brain barrier disruption and neuroinflammation in type 2 diabetic mice

Frontiers in Endocrinology

Endocrinology

Michael Nesbit¹  May Majimbi¹  Ryu Takechi¹  Virginie Lam¹  John Mamo²  Fred K. Chen³  Samuel McLenachan³ 

[1] Curtin Health Innovation Research Institute, Faculty of Health Sciences, Curtin University, Bentley, WA, Australia;Curtin Health Innovation Research Institute, Faculty of Health Sciences, Curtin University, Bentley, WA, Australia;Perron Institute for Neurological and Translational Research, Nedlands, WA, Australia;Lions Eye Institute Australia, Harry Perkins Institute of Medical Research, Nedlands, WA, Australia;

关键词: diabetic cognitive decline;    blood brain barrier;    correlation;    neuroinflammation;    oxidative stress;    retina neurodegeneration;   

DOI  :  10.3389/fendo.2023.1224418

 received in 2023-05-17, accepted in 2023-08-15,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionType 2 diabetes (T2D) is associated with chronic inflammation and neurovascular changes that lead to functional impairment and atrophy in neural-derived tissue. A reduction in retinal thickness is an early indicator of diabetic retinopathy (DR), with progressive loss of neuroglia corresponding to DR severity. The brain undergoes similar pathophysiological events as the retina, which contribute to T2D-related cognitive decline.MethodsThis study explored the relationship between retinal thinning and cognitive decline in the LepR db/db model of T2D. Diabetic db/db and non-diabetic db/+ mice aged 14 and 28 weeks underwent cognitive testing in short and long-term memory domains and in vivo retinal imaging using optical coherence tomography (OCT), followed by plasma metabolic measures and ex vivo quantification of neuroinflammation, oxidative stress and microvascular leakage.ResultsAt 28 weeks, mice exhibited retinal thinning in the ganglion cell complex and inner nuclear layer, concomitant with diabetic insulin resistance, memory deficits, increased expression of inflammation markers and cerebrovascular leakage. Interestingly, alterations in retinal thickness at both experimental timepoints were correlated with cognitive decline and elevated immune response in the brain and retina.DiscussionThese results suggest that changes in retinal thickness quantified with in vivo OCT imaging may be an indicator of diabetic cognitive dysfunction and neuroinflammation.

【 授权许可】

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Copyright © 2023 Majimbi, McLenachan, Nesbit, Chen, Lam, Mamo and Takechi