[The state of ocular neurosensory apparatus in diabetes mellitus]. / Sostoianie neirosensornogo apparata glaza pri sakharnom diabete.

Diabetes mellitus is one of the most common chronic diseases in the world. Among its late complications that can lead to disability is diabetic neuropathy (DN). Patients diagnosed with DN often also have diabetic retinopathy (DR). According to available data, DR prevalence ranges from 30 to 60%. For a long time, DR has been considered a microvascular disease. However, more data has been emerging recently that indicates the presence of other components in the pathophysiology of DR. Neurodegenerative changes in the retina can be detected in patients with diabetes mellitus before clinical signs of diabetic retinopathy appear. Accumulation of extracellular glutamate, oxidative stress, reduction of neuroprotective factors synthesized by the retina are all believed to lead to neuronal apoptosis and glial cell dysfunction. This cascade of reactions subsequently causes disruption of the hematoretinal barrier and damage to neurovascular apparatus of the retina. This results in the defeat of capillaries of the retinal vascular system, which is consistently characterized by the loss of pericytes and the formation of unperfusable capillaries. The concept of neurodegeneration being an early component of DR provides an opportunity to explore alternative therapies to prevent the onset of vision loss in diabetes mellitus.

ID3 contributes to the acquisition of molecular stem cell-like signature in microvascular endothelial cells: its implication for understanding microvascular diseases.

While significant progress has been made to advance our knowledge of microvascular lesion formation, yet the investigation of how stem-like cells may contribute to the pathogenesis of microvascular diseases is still in its infancy. We assessed whether the inhibitor of DNA binding and differentiation 3 (ID3) contributes to the acquisition of a molecular stem cell-like signature in microvascular endothelial cells. The effects of stable ID3 overexpression and SU5416 treatment - a chemical inducer of microvascular lesions, had on the stemness signature were determined by flow cytometry, immunoblot, and immunohistochemistry. Continuous ID3 expression produced a molecular stemness signature consisting of CD133(+) VEGFR3(+) CD34(+) cells. Cells exposed to SU5416 showed positive protein expression of ID3, VEGFR3, CD34 and increased expression of pluripotent transcription factors Oct-4 and Sox-2. ID3 overexpressing cells supported the formation of a 3-D microvascular lesion co-cultured with smooth muscle cells. In addition, in vivo microvascular lesions from SuHx rodent model showed an increased expression of ID3, VEGFR3, and Pyk2 similar to SU5416 treated human endothelial cells. Further investigations into how normal and stem-like cells utilize ID3 may open up new avenues for a better understanding of the molecular mechanisms which are underlying the pathological development of microvascular diseases.

Cognitive functions and white matter lesions on magnetic resonance images in a sample of normal Iranian population with cardiovascular risk factors.

PURPOSE: Due to a suggestive three-way relationship between brain structural disorders, microvascular lesions, and cognitive impairments, we aimed to examine the association of the volume and number of white matter hyperintensity lesions and lacunar infarcts with cognitive impairment among patients with cardiovascular risk factors in a sample of the Iranian population. MATERIALS AND METHODS: This study was conducted on a total number of 156 normal subjects aged 30-74 years with cardiovascular risk factors. We used the Framingham general cardiovascular risk factors prediction model to calculate the likelihood of each risk factor. The total number of lacunar infarcts and the volume of white matter hyperintensity lesion were calculated in brain magnetic resonance imaging. Cognition status was assessed using the Montreal Cognitive Assessment questionnaire. RESULTS: An adverse association was revealed between Montreal Cognitive Assessment score and different cardiovascular risk profiles including the Framingham body mass index score ( p < 0.001) and the Framingham lipid score ( p < 0.001). The total volume of white matter hyperintensity was negatively associated with total Montreal Cognitive Assessment cognition score ( p < 0.001). Our study also showed an adverse association between total number of lacunar infarcts and total Montreal Cognitive Assessment cognition score ( p = 0.038) and with some cognition components including memory ( p = 0.013), attention ( p = 0.037), abstraction ( p = 0.046), and orientation ( p = 0.002). CONCLUSION: Periventricular lesions are associated with impaired memory, language, and visuoconstruction while subcortical lesions are associated with impairment in naming, attention, language, and abstraction functions in normal subjects with cardiovascular risk factors but without cardiovascular or cerebrovascular disorders.