Impaired blood flow in various organs and tissues is a common cause of disabling disorders that even result in a lethal outcome. Despite an extremely rapid development of modern medicine, the rate of these disorders is still high thus emphasizing the importance of further detailed studies on this issue. In addition to systemic vascular diseases, local blood flow disturbances are also prevalent among population. These disturbances result from more significant blood flow disorders. Retinal vein occlusion is not an exclusion. Acute retinal vein occlusions account for more than half of ocular vascular diseases and may lead to extremely severe ophthalmic complications that result in poor vision, blindness, and reduced quality of life in both young and elderly patients. The diversity of clinical presentations, their severity, and clinical course make the diagnosis challenging thus altering the assessment of the prevalence of these diseases. Keywords: retinal vein occlusion, epidemiology, systemic vascular disorders, risk factors, retinal vessels. For citation: Moshetova L.К., Usharova S.А., Simonova S.V.,Turkina К.I. Epidemiology of retinal vein occlusions: state-of-the-art. Russian Journal of Clinical Ophthalmology. 2021;21(2):86–89. DOI: 10.32364/2311-7729-2021-21-2-86-89.
Tear samples collected from patients with central retinal vein occlusion (CRVO; n = 28) and healthy volunteers (n = 29) were analyzed using a proteomic label-free absolute quantitative approach. A large proportion (458 proteins with a frequency > 0.6) of tear proteomes was found to be shared between the study groups. Comparative proteomic analysis revealed 29 proteins (p < 0.05) significantly differed between CRVO patients and the control group. Among them, S100A6 (log (2) FC = 1.11, p < 0.001), S100A8 (log (2) FC = 2.45, p < 0.001), S100A9 (log2 (FC) = 2.08, p < 0.001), and mesothelin ((log2 (FC) = 0.82, p < 0.001) were the most abundantly represented upregulated proteins, and β2-microglobulin was the most downregulated protein (log2 (FC) = −2.13, p < 0.001). The selected up- and downregulated proteins were gathered to customize a map of CRVO-related critical protein interactions with quantitative properties. The customized map (FDR < 0.01) revealed inflammation, impairment of retinal hemostasis, and immune response as the main set of processes associated with CRVO ischemic condition. The semantic analysis displayed the prevalence of core biological processes covering dysregulation of mitochondrial organization and utilization of improperly or topologically incorrect folded proteins as a consequence of oxidative stress, and escalating of the ischemic condition caused by the local retinal hemostasis dysregulation. The most significantly different proteins (S100A6, S100A8, S100A9, MSLN, and β2-microglobulin) were applied for the ROC analysis, and their AUC varied from 0.772 to 0.952, suggesting probable association with the CRVO.
Tear samples were collected from 88 subjects and analyzed using absolute quantitative and comparative proteomic approach. We found a large proportion (505 proteins) of tear proteome between healthy donors and subjects with retinal vein occlusion (RVO). Comparative proteomic analysis revealed 30 proteins (p<0.05) significantly differed in their quantitative property. Among them S100A6 (3.7 fmoles/ng, p<0.001), S100A8 (0.68 fmoles/ng, p<0.001), and S100A9 (2.06 fmoles/ng, p<0.001) are the most overrepresented proteins. Mesothelin was found as tear-specific protein with significant increase (1.08 fmoles/ng versus 0.54 fmoles/ng in the control, p<0.001) in the RVO group. The selected altered proteins were combined to reconstruct the customized map of protein-protein interactions with the burden of quantitating property and the context of RVO-related association. The customized interactions map (FDR<0.01) emerged inflammation and impartment of retinal hemostasis as the main RVO-associated processes. The semantic analysis of customized map encouraged the prevalence of core biological processes encompassing dysregulation of mitochondrial organization and utilization of topologically incorrect folded proteins as a consequence of oxidative stress and inflammation caused by the retinal ischemic condition. Significantly differed proteins (S100A6, S100A8, S100A9, MSL, B2M) were applied for the ROC plotting with AUC varied from 0.772 to 0.952 suggesting their association with the CRVO.
The disruption of blood flow through the retinal vessels is undoubtedly a stressful situation for the body. In response to any stress, the body produces heat shock proteins or so-called stress proteins. Moreover, a number of modern studies indicate that HSP may act as autoantigens, which are components of the immune system involved in the pathogenesis of vascular pathologies. By now, a number of certain heat shock proteins (HSP 60, 70) have already been proven to play a significant role in the pathogenesis of atherosclerosis as well as various circulatory disorders in the cerebral vessels. In addition, the possibility of using the data on the content and concentration of certain HSPs and antibodies to them in the blood plasma of patients as diagnostic and prognostic markers of systemic vascular diseases is considered. On the visual organ side, HSPs have been found to have damaging effects on retinal ganglion cells and, together with antibodies produced in response to their presence, are involved in the pathogenesis of glaucoma. However, there is currently no data on the role of HSP in the pathogenesis of retinal blood flow disorders and the possibility of using these molecules as diagnostic or prognostic markers of such conditions.
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