Abstract
Purpose :
Type 2 diabetes (T2D) accounts for more than 90% of all diabetes cases worldwide. An association between T2D and dementia has been reported in the literature. Diabetes is known to affect the microvasculature in both the brain and the retina. However, the pathophysiology of the complex cell-cell interactions in the blood-brain barrier and blood-retinal barrier remains poorly understood, particularly concerning the vascular aspects of the neurovascular unit (NVU).
Methods :
Human post-mortem eyes from T2D or diabetic retinopathy (DR) patients and brains from T2D and dementia patients were sectioned. Expression of selective NVU markers for vascular cells, perivascular cells, glial cells, tight junctions and vascular leakage were investigated using immunofluorescence staining followed by confocal microscopy.
Results :
In diabetes and dementia, we found that the NVU pathology of the brain is similar to that in the retina based on immunofluorescence analysis. We observed an increase in extravascular fibrinogen, indicating vascular leakage in the diabetic retina and demented brain compared with their non-diabetic and non-demented controls. By studying the tight junctions of the NVU, we detected a sharply localized occludin staining in control retina at the cell border of adjacent endothelial cells, whereas in the DR retina a reduced and more intracellular expression was observed. A similar expression pattern was found in the diabetic and demented brain. Furthermore, astrocyte loss was indicated by reduced glial fibrillary acidic protein (GFAP) expression around capillaries in the DR retina, whereas increased GFAP expression in retinal Müller cell axons suggested gliosis. For the diabetic and demented brain, the number of GFAP+ cells was increased. Since astrocytes are crucial in the water and ion balance of neuronal tissue, we also studied astrocytic water and potassium channels, both of which were affected in pathology in the brain and retina.
Conclusions :
The immunofluorescence staining of markers of the NVU provide further evidence for similar dysfunction in the vascular facet of the NVU in the retina and brain for T2D and dementia. Our findings will contribute to the identification of molecular links between the retina and brain in terms of NVU impairment that occurs in T2D and dementia.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.