Retinal microcirculation: A window into systemic circulation and metabolic disease.

The retinal microcirculation system constitutes a unique terminal vessel bed of the systemic circulation, and its perfusion status is directly associated with the neural function of the retina. This vascular network, essential for nourishing various layers of the retina, comprises two primary microcirculation systems: the retinal microcirculation and the choroidal microcirculation, with each system supplying blood to distinct retinal layers and maintaining the associated neural function. The blood flow of those capillaries is regulated via different mechanisms. However, a range of internal and external factors can disrupt the normal architecture and blood flow within the retinal microcirculation, leading to several retinal pathologies, including diabetic retinopathy, macular edema, and vascular occlusions. Metabolic disturbances such as hyperglycemia, hypertension, and dyslipidemia are known to modify retinal microcirculation through various pathways. These alterations are observable in chronic metabolic conditions like diabetes, coronary artery disease, and cerebral microvascular disease due to advances in non-invasive or minimally invasive retinal imaging techniques. Thus, examination of the retinal microcirculation can provide insights into the progression of numerous chronic metabolic disorders. This review discusses the anatomy, physiology and pathophysiology of the retinal microvascular system, with a particular emphasis on the connections between retinal microcirculation and systemic circulation in both healthy states and in the context of prevalent chronic metabolic diseases.

Changes and clinical significance of plasma S100A1 protein, nuclear factor-κB p65 and interleukin-6 levels in patients with acute ischemic cerebrovascular diseases / 中国基层医药

Objective:To investigate the changes and clinical significance of plasma S100A1 protein, nuclear factor-κB p65 (NF-κB p65) and interleukin-6 (IL-6) levels in patients with acute ischemic cerebrovascular diseases.Methods:A total of 141 patients with acute ischemic cerebral infarction (AICI; AICI group) and 20 patients with transient ischemic attack (TIA; TIA group) who received treatment in Northern Jiangsu People's Hospital from April to November 2020 were included in this study. According to the volume of cerebral infarct, the AICI group was subdivided into small-volume cerebral infarct (SCI group, n = 78), moderate-volume cerebral infarct (MCI group, n = 32) and large-volume cerebral infract (LCI group, n = 31) groups. An additional 31 healthy controls who concurrently received physical examination were included as controls (HC group). S100A1, NF-κB p65, and IL-6 levels were compared between AICI, TIA and HC groups and between SCI, MCI and LCI groups. S100A1, NF-κB p65, and IL-6 levels were correlated with the National Institutes of Health Stroke Scale score and the volume of cerebral infarct. The receiver operating characteristic curve (ROC) was drawn to analyze the diagnostic value of S100A1, NF-κB p65, and IL-6 levels for AICI. Results:S100A1, NF-κB p65, and IL-6 levels in the AICI group were (230.96 ± 39.37) ng/L, (3.99 ± 0.65) mg/L, (13.32 ± 1.57) ng/L, respectively, which were significantly higher than (185.85 ± 43.24) ng/L, (3.58 ± 0.74) mg/L, (11.61 ± 1.67) ng/L in the TIA group ( t = 4.95, 2.39, 4.14, all P < 0.05) and (181.47 ± 27.39) ng/L, (3.51 ± 0.99) mg/L, (11.42 ± 2.34) ng/L in the HC group ( t = 6.54, 3.32, 5.55, all P < 0.05). There were no significant differences in S100A1, NF-κB p65, and IL-6 levels between TIA and HC groups (all P > 0.05). S100A1, NF-κB p65, and IL-6 levels in the LCI group were (254.25 ± 37.07) ng/L, (4.41 ± 0.45) mg/L, and (14.00 ± 1.40) ng/L, respectively, which were significantly higher than (225.42 ± 30.92) ng/L, (3.85 ± 0.64) mg/L, (12.77 ± 1.31) ng/L in the MCI group ( t = 3.04, 3.60, 3.20, all P < 0.05) and (223.98 ± 40.21) ng/L, (3.88 ± 0.66) mg/L, (13.27 ± 1.65) ng/L in the SCI group ( t = 3.79, 4.01, 2.25, all P < 0.05). There were no significant differences in S100A1, NF-κB p65, and IL-6 levels between MCI and SCI groups (all P > 0.05). S100A1 and NF-κB p65 levels in patients with AICI were positively correlated with the volume of cerebral infarct ( r = 0.24, 0.27, both P < 0.05). S100A1 and IL-6 levels in patients with AICI were positively correlated with the National Institutes of Health Stroke Scale score ( r = 0.24, 0.28, both P < 0.05). The areas under the curves plotting S100A1, NF-κB p65, and IL-6 levels against AICI diagnosis were 0.818, 0.667 and 0.754, respectively. The optimal cutoff values were 181.03, 3.50 and 10.79, respectively. The corresponding sensitivities were 95.0%, 76.6% and 97.2%, respectively, and the specificities were 37.3%, 45.1% and 49.0%, respectively. Conclusion:Increased S100A1, NF-κB p65, and IL-6 levels in patients with AICI are closely related to the severity of AICI.

Periodic Limb Movements Syndrome in Patients With Cerebral Small Vessel Disease: Protocol for a Prospective Observational Study.

Background: Cerebrovascular diseases are the leading cause of cognitive decline and dementia. Therefore, the investigation of the potential ways to slow down the disease progression is an important research field. Periodic limb movements in sleep (PLMS) are known to be associated with transient changes in heart rate and blood pressure. These changes might influence the course of cerebral small vessel disease (cSVD). Nevertheless, the clinical significance of PLMS, particularly its influence on cardiovascular diseases course, is still controversial and underinvestigated. Methods/design: Patients from 60 to 75 years old diagnosed with cSVD will undergo nocturnal polysomnography. Subjects with apnea/hypopnea index under 5 will be enrolled. Sleep quality and daytime functioning will be assessed at baseline with self-reported questionnaires. Brain MRI and cognitive assessment will be performed at baseline and in the 2-year follow-up. Progression of cSVD markers and cognitive dysfunction will be compared between patients with PLMS index (PLMI) equal to or more than 15 movements per hour of sleep and controls (PLMI <15/h). Discussion: The negative role of PLMS in cSVD progression and related cognitive decline is expected. We suppose that patients with PLMS tend to worsen in cognitive performance more rapidly than age-, gender-, and comorbidity-matched controls. We also expect them to have more rapid white matter hyperintensities and other cSVD marker progression. The limitations of the study protocol are the short follow-up period, the absence of a treatment group, and inability to make a conclusion about causality.

Cystatin C in Cerebrovascular Disorders.

Cystatin C (CysC), a cysteine protease inhibitor, has been widely proven to be a highly sensitive biomarker to predict the kidney function. The similarity of the renal and cerebral small vessels has awakened a surge of studies suggesting that CysC plays a key role in various cerebrovascular disorders. This review focuses on four major mechanisms of CysC in a variety of cerebrovascular diseases. (1) The property of the CysC Leu-68-Gln (L68Q) variant to aggregate and the property of the wild type CysC protein to co-aggregate with Amyloid-ß (Aß); (2) The disruption of equilibrium between CysC and related cysteine proteases; (3) The function of CysC as an inflammatory inducing factor; (4) The ability of CysC to induce autophagy. The combination of these CysC properties provides a well-supported novel biomarker for cerebrovascular diseases.