Occipital blood‐brain barrier permeability is an independent predictor of visual outcome in type 2 diabetes, irrespective of the retinal barrier: A longitudinal study

Abstract

Blood‐brain barrier (BBB) permeability in type 2 diabetic patients has been previously shown to be altered in certain brain regions such as the basal ganglia and the hippocampus. Because of the histological and functional similarities between the BBB) and the blood‐retinal barrier (BRB), we aimed to investigate how the permeability of both barriers predicts visual outcome. We included 2 control groups (acute unilateral stroke patients, n = 9; type 2 diabetics without BRB leakage n = 10) and a case study group of type 2 diabetics with established BRB leakage (n = 17). We evaluated sex, age, disease duration, metabolic impairment, retinopathy grade and BBB permeability as predictors of visual acuity at baseline, 12 and 24 months in the type 2 diabetics without BRB leakage group and the case study group. We have also explored differences in BBB permeability in the occipital lobe and frontal lobe in the 3 different groups. Ktrans (volume transfer coefficient) and Vp (fractional plasma volume) were estimated. The BBB permeability parameter Vp was higher in the case study group compared to the unaffected hemisphere of the stroke patient control group, suggesting vascular dynamics were changed in the occipital lobe of type 2 diabetics with established BRB leakage. These patients showed a significant correlation between glycated hemoglobin (HbA1C) levels and occipital and frontal Ktrans. We report for the first time that occipital BBB permeability is an independent predictor of visual acuity at baseline, as well as at 12 and 24 months, in type 2 diabetics with established BRB leakage. Our results suggest that occipital BBB permeability might be an independent biomarker for visual impairment in patients with established BRB leakage.

A New Human Blood–Retinal Barrier Model Based on Endothelial Cells, Pericytes, and Astrocytes

“…In particular, co-cultures of BRB are widely used in order to clarify the cross-talk between the cells of the retinal unit. According to Nakagawa et al, in vitro models of rat blood-brain barrier (BBB), in which endothelial cells and pericytes are co-cultured on opposite sides of a transwell insert and astrocytes are located at the bottom of the culture dish, well represent the in vivo anatomical position of the cells at the BBB [38], which, as is well-known, shares histological and functional similarities with the BRB [39]. Recently, Wisniewska-Kruk et al [40] set up a BRB model based on a triple co-culture, even though they did not used human cells.…”

Alzheimer's disease pathology: pathways between chronic vascular risk factors and blood-brain barrier dysfunction in a cohort of patients with different types of dementia

“…Janelidze et al ( 2017 ) reported a higher Qalb in individuals with T2DM compared with subjects without T2DM in two different cohorts with a total of 1,015 subjects, and the authors demonstrated that T2DM was associated with high CSF levels of intercellular adhesion molecule-1 ( p < 0.001), vascular cellular adhesion molecule-1 ( p = 0.007), and vascular endothelial-derived growth factor ( p = 0.024), CSF biomarkers of angiogenesis and endothelial dysfunction. Individuals with T2DM also showed increased BBB permeability in basal ganglia (Starr et al, 2003 ), hippocampus, occipital lobe, and frontal lobe (Abuhaiba et al, 2018 ) based on DCE-MRI. Furthermore, significant correlations were found between occipital (R = 0.612, p = 0.013) or frontal K trans (R = 0.579, p = 0.019) and GHb level (Abuhaiba et al, 2018 ), a marker indicating the long-term status of blood glucose.…”

“…Individuals with T2DM also showed increased BBB permeability in basal ganglia (Starr et al, 2003 ), hippocampus, occipital lobe, and frontal lobe (Abuhaiba et al, 2018 ) based on DCE-MRI. Furthermore, significant correlations were found between occipital (R = 0.612, p = 0.013) or frontal K trans (R = 0.579, p = 0.019) and GHb level (Abuhaiba et al, 2018 ), a marker indicating the long-term status of blood glucose. Wang et al ( 2020 ) reported the BBB breakdown in the hippocampus, white matter, and cortex inferior temporal gyrus in syphilis individuals with high GHb levels.…”

The retina-brain axis and diabetic retinopathy

“…Diabetes induces changes to the BBB and BRB, whereas AD causes changes to the BBB. 139 In AD and diabetes, impaired tight junction, pericyte dysfunction, astrocyte dysfunction, endothelial dysfunction, disease of the basement membrane, and increased permeability are markers of the BBB and BRB collapse. 26,[140][141][142][143][144][145][146][147][148][149] When the BBB is compromised, inflammatory leukocytes (white blood cells) and amyloid deposits enter the brain.…”