Proteomic analysis of early diabetic retinopathy reveals mediators of neurodegenerative brain diseases

© 2018 The Authors. PURPOSE. Current evidence suggests that retinal neurodegeneration is an early event in the pathogenesis of diabetic retinopathy. Our main goal was to examine whether, in the diabetic human retina, common proteins and pathways are shared with brain neurodegenerative diseases. METHODS. A proteomic analysis was performed on three groups of postmortem retinas matched by age: nondiabetic control retinas (n = 5), diabetic retinas without glial activation (n = 5), and diabetic retinas with glial activation (n = 5). Retinal lysates from each group were pooled and run on an SDS-PAGE gel. Bands were analyzed sequentially by liquid chromatography-mass spectrometry (LC/MS) using an Orbitrap Mass Spectrometer. RESULTS. A total of 2190 proteins were identified across all groups. To evaluate the association of the identified proteins with neurological signaling, significant signaling pathways belonging to the category ‘‘Neurotransmitters and Other Nervous System Signaling” were selected for analysis. Pathway analysis revealed that ‘‘Neuroprotective Role of THOP1 in Alzheimer’s Disease” and ‘‘Unfolded Protein Response” pathways were uniquely enriched in control retinas. By contrast, ‘‘Dopamine Degradation” and ‘‘Parkinson’s Signaling” were enriched only in diabetic retinas with glial activation. The ‘‘Neuregulin Signaling,” “Synaptic Long Term Potentiation,” and “Amyloid Processing” pathways were enriched in diabetic retinas with no glial activation. CONCLUSIONS. Diabetes-induced retinal neurodegeneration and brain neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases, share common pathogenic pathways. These findings suggest that the study of neurodegeneration in the diabetic retina could be useful to further understand the neurodegenerative processes that occur in the brain of persons with diabetes

Diabetic retinopathy as an independent predictor of subclinical cardiovascular disease : Baseline results of the PRECISED study

Càrrega feta de Scopus d'articles UAB 2019 (Gold, hybrid o Bronze) procedents de l'Observatori d'Accés Obert (càrrega maig 2020). Compte! Cal comprovar la versió permesa per l'editor en els bronze.Funding This work was supported by an Integrative Excellence Project by the Spanish Institute of Health, Instituto de Salud Carlos III, grant PIE 2013/27, CIBER CV, CIBERDEM, and the European Regional Development Fund (ERDF-FEDER). The Neurovascular Research Laboratory is part of the Spanish Stroke Research Network INVICTUS+ (RD16/0019/0021).Objective Detection of subclinical cardiovascular disease (CVD) has significant impact on the management of type 2 diabetes. We examined whether the assessment of diabetic retinopathy (DR) is useful for identifying patients at a higher risk of having silent CVD. Research design and methods Prospective case-control study comprising 200 type 2 diabetic subjects without history of clinical CVD and 60 age-matched non-diabetic subjects. The presence of subclinical CVD was examined using two parameters: (1) calcium coronary score (CACs); (2) composite of CACs >400 UA, carotid plaque ≥3 mm, carotid intima-media thickness ratio >1, or the presence of ECG changes suggestive of previous asymptomatic myocardial infarction. In addition, coronary angio-CT was performed. DR was assessed by slit-lamp biomicroscopy and retinography. Results Type 2 diabetic subjects presented higher CACs than non-diabetic control subjects (p400 (area under the receiver operating characteristic curve (AUROC) 0.76). In addition, an inverse relationship was observed between the degree of DR and CACs <10 AU. The variables independently associated with the composite measurement of subclinical CVD were age, diabetes duration, the glomerular filtration rate, microalbuminuria, and the presence of DR (AUROC 0.71). In addition, a relationship (p<0.01) was observed between the presence and degree of DR and coronary stenosis. Conclusions The presence and degree of DR is independently associated with subclinical CVD in type 2 diabetic patients. Our results lead us to propose a rationalized screening for coronary artery disease in type 2 diabetes based on prioritizing patients with DR, particularly those with moderate-severe degree

Common pathways in dementia and diabetic retinopathy: understanding the mechanisms of diabetes-related cognitive decline.

Type 2 diabetes (T2D) is associated with multiple comorbidities, including diabetic retinopathy (DR) and cognitive decline, and T2D patients have a significantly higher risk of developing Alzheimer's disease (AD). Both DR and AD are characterized by a number of pathological mechanisms that coalesce around the neurovascular unit, including neuroinflammation and degeneration, vascular degeneration, and glial activation. Chronic hyperglycemia and insulin resistance also play a significant role, leading to activation of pathological mechanisms such as increased oxidative stress and the accumulation of advanced glycation end-products (AGEs). Understanding these common pathways and the degree to which they occur simultaneously in the brain and retina during diabetes will provide avenues to identify T2D patients at risk of cognitive decline