Arteriolar Diameter Research Articles

Influence of pneumoperitoneum and head-down maneuver on the cerebral microvasculature in rabbits

BackgroundWith recent advances in robot-assisted techniques, an increasing number of surgeries are being performed with pneumoperitoneum and head-down maneuver (HDM) that may affect the cerebral microcirculation. For the first time, this study investigated the direct influence of pneumoperitoneum and HDM on the cerebral microvasculature in rabbits.MethodsAdult male rabbits were randomly allocated to the following groups (n = 7 each): control, pneumoperitoneum alone (P), and pneumoperitoneum with HDM (P + HDM) for 120 min. A closed cranial window was installed above the parietal bone to visualize the pial microvasculature. Pial arteriolar diameter and hemodynamic and blood gas parameters were measured during the 140-min observation period. Brain edema was assessed by evaluation of the brain water content at the end of the experiment.ResultsRabbits in the P and P + HDM groups exhibited a similar degree of immediate pial arteriolar dilation following the initiation of both P and P + HDM (P: 1.11 ± 0.03, p = 0.0044 and P + HDM: 1.07 ± 0.02, p = 0.0004, relative changes from the baseline value by defining the baseline as one). In the P + HDM group, pial arteriole diameter returned to the baseline level following the discontinuation of pneumoperitoneum and HDM (1.05 ± 0.03, p = 0.0906, vs. baseline). In contrast, the pial arterioles remained dilated as compared to the baseline level in the P group after discontinuation of pneumoperitoneum. There were no changes in pial arteriole diameter in the animals in the control group. Heart rate, blood gas parameters, and brain water content were not significantly different between the groups.ConclusionThe pial arterioles dilated immediately after pneumoperitoneum with or without HDM. The pial arterioles remained dilated 20 min after discontinuation of pneumoperitoneum alone but constricted upon discontinuation of pneumoperitoneum plus HDM. Pneumoperitoneum and HDM for 2 h did not cause brain edema.

Praliciguat Promotes Ischemic Leg Reperfusion in Leptin Receptor-Deficient Mice.

Lower-limb peripheral artery disease is one of the major complications of diabetes. Peripheral artery disease is associated with poor limb and cardiovascular prognoses, along with a dramatic decrease in life expectancy. Despite major medical advances in the treatment of diabetes, a substantial therapeutic gap remains in the peripheral artery disease population. Praliciguat is an orally available sGC (soluble guanylate cyclase) stimulator that has been reported both preclinically and in early stage clinical trials to have favorable effects in metabolic and hemodynamic outcomes, suggesting that it may have a potential beneficial effect in peripheral artery disease. We evaluated the effect of praliciguat on hind limb ischemia recovery in a mouse model of type 2 diabetes. Hind limb ischemia was induced in leptin receptor-deficient (Leprdb/db) mice by ligation and excision of the left femoral artery. Praliciguat (10 mg/kg/day) was administered in the diet starting 3 days before surgery. Twenty-eight days after surgery, ischemic foot perfusion and function parameters were better in praliciguat-treated mice than in vehicle controls. Improved ischemic foot perfusion was not associated with either improved traditional cardiovascular risk factors (ie, weight, glycemia) or increased angiogenesis. However, treatment with praliciguat significantly increased arteriole diameter, decreased ICAM1 (intercellular adhesion molecule 1) expression, and prevented the accumulation of oxidative proangiogenic and proinflammatory muscle fibers. While investigating the mechanism underlying the beneficial effects of praliciguat therapy, we found that praliciguat significantly downregulated Myh2 and Cxcl12 mRNA expression in cultured myoblasts and that conditioned medium form praliciguat-treated myoblast decreased ICAM1 mRNA expression in endothelial cells. These results suggest that praliciguat therapy may decrease ICAM1 expression in endothelial cells by downregulating Cxcl12 in myocytes. Our results demonstrated that praliciguat promotes blood flow recovery in the ischemic muscle of mice with type 2 diabetes, at least in part by increasing arteriole diameter and by downregulating ICAM1 expression.

MORPHOLOGICAL CHARACTERISTICS OF THE TRIGEMINAL NODE OF RATS WHEN CRYOPRESERVED PLACENTA IS INTRODUCED

Cryopreserved placenta preparations have a unique composition of biologically active substances, which determines their multifaceted effect. The aim of our study was to investigate the morphological features of the trigeminal node of rats when cryopreserved placenta was injected.
 The conducted experimental study showed that a single subcutaneous injection of cryopreserved placenta causes a reaction of the vessels of the microcirculatory bed of the trigeminal node of rats in the first two weeks of observation in the form of an expansion of the diameter of arterioles, capillaries and venules and an increase in blood filling, which indicates the stimulating effect of the components of the fetoplacental complex on the microcirculatory bed. The most pronounced phenomena were observed on the 7th day.
 After transplantation of the cryopreserved placenta, the neurocytes of the trigeminal node had a large, well-defined light nucleus, well-defined cytoplasm, with deep chromatophilic substance, there were dark, smaller cells with dispersed Nissl substance, satellite cells, and nerve fibers remained intact during all observation periods.
 The obtained data confirm the trophic effect of drugs of the fetoplacental complex. Our experimental study showed that a single subcutaneous injection of cryopreserved placenta causes a reaction of the vessels of the microcirculatory bed of the trigeminal node of rats in the first two weeks of observation in the form of an expansion of the diameter of arterioles, capillaries and venules and an increase in blood filling. The most pronounced phenomena were observed on the 7th day. The obtained data indicate the stimulating effect of the components of the fetoplacental complex on the microcirculatory channel.
 After transplantation of the cryopreserved placenta, neurocytes, satellite cells, and nerve fibers remained intact during all observation periods.

Особливості комп’ютерного аналізу біомедичних зображень мікроциркуляції кон’юнктиви ока

An analysis was carried out, which showed that the task of creating a system for evaluating biomedical images of pathologies of the vessels of the human eye is relevant and needs to be solved, since the existing methods and systems of evaluation, as well as the existing methods of processing biomedical images do not meet the modern requirements for such systems in terms of accuracy , the reliability of processing biomedical images, which leads to the occurrence of errors in the diagnosis in ophthalmological studies. The results of the comparison of the effectiveness of the Kirsch, Sobel, Roberts, Wallace, SUSAN algorithms for processing biomedical images based on the set of information diagnostic features formed are the most informative for image segmentation, the algorithms based on Kirsch filtering and the nonlinear Sobel filter. A system has been developed for evaluating dynamic changes in biomedical images, which allows to evaluate the state of blood vessels and determine the conjunctival index based on the following indicators: the ratio of the diameters of arterioles and corresponding venules; caliber irregularities; meander windings; microaneurysms; glomeruli; reticular structures of vessels; changes in the number of functioning capillaries; arteriolo-venular anastomoses; hemorrhages; perivascular edema; sludge phenomena; microthrombi

Plasticity of cerebral microvascular structure and mechanics during hypertension and following recovery of arterial pressure.

Changes in vascular structure contribute to vascular events and loss of brain health. We examined changes in cerebral arterioles at the onset of hypertension and the hypothesis that alterations during hypertension would recover with the return of mean arterial pressure (MAP) to normal. MAP was measured with radiotelemetry in awake male C57BL/6J mice at baseline and during infusion of vehicle or angiotensin II (ANG II, 1.4 mg/kg/day using osmotic pumps) for 28 days, followed by a 28-day recovery. With ANG II treatment, MAP increased through day 28. On day 30, MAP began to recover, reaching levels not different from vehicle on day 37. We measured intravascular pressure, diameter, wall thickness (WT), wall:lumen ratio (W:L), cross-sectional area (CSA), and slope of the tangential elastic modulus (ET) in maximally dilated arterioles. Variables were similar in both groups at day 1, with no significant change with vehicle treatment. With ANG II treatment, CSA, WT, and W:L increased on days 7-28. Internal and external diameter was reduced at 14 and 28 days. ET versus wall stress was reduced on days 7-28. During recovery, the diameter remained at days 14 and 28 values, whereas other variables returned partly or completely to normal. Thus, CSA, WT, W:L, and ET versus wall stress changed rapidly during hypertension and recovered with MAP. In contrast, inward remodeling developed slowly and did not recover. This lack of recovery has mechanistic implications for the long-term impact of hypertension on vascular determinants of brain health.NEW & NOTEWORTHY Changes in vascular structure contribute to vascular events and loss of brain health. We examined the inherent structural plasticity of cerebral arterioles during and after a period of hypertension. Arteriolar wall thickness, diameter, wall-to-lumen ratio, and biological stiffness changed rapidly during hypertension and recovered with blood pressure. In contrast, inward remodeling developed slowly and did not recover. This lack of recovery of arteriolar diameter has implications for the long-term impact of hypertension on vascular determinants of brain health.

Role of Prostaglandins in Nitric Oxide-Induced Glial Cell-Mediated Vasodilation in Rat Retina.

We previously identified that NO derived from neuronal cells acts on glial cells and causes vasodilation in the healthy rat retina via the release of epoxyeicosatrienoic acids (EETs) and prostaglandins (PGs) by activation of the arachidonic acid cascade. However, it is not clear which PG types are involved in these responses. The aim of the present study was to identify prostanoid receptors involved in glial cell-derived vasodilation induced by NO in rat retina. Male Wistar rats were used to examine the effects of intravitreal pretreatment with indomethacin, a cyclooxygenase inhibitor; PF-04418948, a prostanoid EP2 receptor antagonist; and CAY10441, a prostanoid IP receptor antagonist, on the changes in the retinal arteriolar diameter induced by intravitreal administration of NOR3, an NO donor. Retinal arteriolar diameters were measured using ocular fundus images captured with a high-resolution digital camera in vivo. The increase in the retinal arteriolar diameter induced by intravitreal injection of NOR3 was significantly suppressed by intravitreal pretreatment with indomethacin and PF-04418948, but not by CAY10441. The dose of PF-04418948 and CAY10441 injected intravitreally in the present study significantly reduced the increase in the retinal arteriolar diameter induced by prostaglandin E2 (PGE2) and prostaglandin I2 (PGI2), respectively. These results suggest that activation of the arachidonic acid cascade and subsequent stimulation of prostanoid EP2 receptors are involved in rat retinal vasodilatory responses evoked by NO-induced glial cell stimulation. Therefore, glial cell-derived PGE2, similar to EETs, may play an important role in retinal vasodilatory mechanisms.

Neurovascular correlates of retinal microvascular caliber in adolescent bipolar disorder

BackgroundThe connection between vascular and brain metrics is well-studied in older adults, but neglected in youth and in psychiatric populations at increased cardiovascular risk. We therefore examined the association of retinal vascular caliber with cerebral blood flow (CBF) in adolescents with and without bipolar disorder (BD). MethodsNinety-four adolescents (n = 48 BD, n = 46 controls) completed retinal fundus imaging, yielding estimates of arteriolar and venular diameter. Arterial spin labelling MRI was performed to measure CBF. We tested for associations between retinal vascular caliber and CBF in regions of interest; anterior cingulate cortex (ACC), middle frontal gyrus, and hippocampus in BD and controls separately. Complementary voxel-wise analyses were also performed. ResultsIn the BD group, higher arteriovenous ratio (AVR) was associated with greater ACC CBF (β = 0.34, puncorrected = 0.02), after controlling for age, sex, and BMI, however this finding did not survive correction for multiple comparisons. The control group did not show any associations (β = 0.13, puncorrected = 0.40). Voxel-wise analyses within the BD group detected a significant positive association between AVR and regional CBF in two distinct clusters: i) left hippocampus (p < 0.0001); ii) right middle temporal gyrus (p = 0.04). LimitationsLimited sample size; young, medically healthy sample limits signal detection; cross-sectional design. ConclusionThis study reveals that higher AVR is associated with higher regional CBF in adolescents with BD. Present findings advance understanding of potential neurofunctional mechanisms linking retinal vascular caliber with psychiatric diagnoses. This proof-of-concept study was designed to generate initial insights to guide future studies focusing on the vascular-brain connection in youth and in psychiatry.

Non-Invasive Metabolic and Structural Retinal Markers in Patients with Giant Cell Arteritis and Polymyalgia Rheumatica: A Cross-Sectional Study.

Giant cell arteritis (GCA) is a potential sight-threatening disease. Although it is associated with polymyalgia rheumatica (PMR), visual loss is not common in PMR. A retinal oximeter can be used to conduct a direct, non-invasive, in vivo assessment of the vascular system. In a cross-sectional study, we measured the retinal oxygen saturation and retinal vessel calibers in GCA patients, PMR patients, and control participants. Twenty GCA patients (38 eyes), 19 PMR patients (33 eyes), and 12 controls (20 eyes) were investigated. Images were analyzed using Oxymap Analyzer software 2.5.0 (Oxymap ehf., Reykjavik, Iceland). Groups were compared using an age- and sex-adjusted linear mixed model regression. The median (IQR) age for GCA patients was 69.0 (66.5–76.5) years, for PMR 69.0 (67.0–72.0) years, and for the controls 75.5 (71.5–81.0) years, respectively. As compared to the controls (115.3 µm), the retinal arterioles were significantly wider in patients with GCA (124.4 µm; p = 0.023) and PMR (124.8 µm; p = 0.049). No difference was found in the retinal venular caliber or vascular oxygen saturation. These results indicate that GCA and PMR patients differ similarly in the retinal arteriolar diameter compared to controls. Further studies are needed in order to clarify the underlying inflammatory mechanisms in retinal arteriolar vessels and if these parameters can be used to predict clinical outcomes.

3D optogenetic control of arteriole diameter in vivo.

Modulation of brain arteriole diameter is critical for maintaining cerebral blood pressure and controlling regional hyperemia during neural activity. However, studies of hemodynamic function in health and disease have lacked a method to control arteriole diameter independently with high spatiotemporal resolution. Here, we describe an all-optical approach to manipulate and monitor brain arteriole contractility in mice in three dimensions using combined in vivo two-photon optogenetics and imaging. The expression of the red-shifted excitatory opsin, ReaChR, in vascular smooth muscle cells enabled rapid and repeated vasoconstriction controlled by brief light pulses. Two-photon activation of ReaChR using a spatial light modulator produced highly localized constrictions when targeted to individual arterioles within the neocortex. We demonstrate the utility of this method for examining arteriole contractile dynamics and creating transient focal blood flow reductions. Additionally, we show that optogenetic constriction can be used to reshape vasodilatory responses to sensory stimulation, providing a valuable tool to dissociate blood flow changes from neural activity.

Intravital imaging of hemodynamic glomerular effects of enalapril or/and empagliflozin in STZ-diabetic mice.

Background: Diabetic kidney disease is the leading cause of end-stage renal disease. Administration of ACE inhibitors or/and SGLT2 inhibitors show renoprotective effects in diabetic and other kidney diseases. The underlying renoprotective mechanisms of SGLT2 inhibition, especially in combination with ACE inhibition, are incompletely understood. We used longitudinal intravital microscopy to directly elucidate glomerular hemodynamics on a single nephron level in response to the ACE inhibitor enalapril or/and the SGLT2 inhibitor empagliflozin. Methods: Five weeks after the induction of diabetes by streptozotocin, male C57BL/6 mice were treated with enalapril, empagliflozin, enalapril/empagliflozin or placebo for 3 days. To identify hemodynamic regulation mechanisms, longitudinal intravital multiphoton microscopy was employed to measure single nephron glomerular filtration rate (snGFR) and afferent/efferent arteriole width. Results: Diabetic mice presented a significant hyperfiltration. Compared to placebo treatment, snGFR was reduced in response to enalapril, empagliflozin, or enalapril/empagliflozin administration under diabetic conditions. While enalapril treatment caused significant dilation of the efferent arteriole (12.55 ± 1.46 µm vs. control 11.92 ± 1.04 µm, p < 0.05), empagliflozin led to a decreased afferent arteriole diameter (11.19 ± 2.55 µm vs. control 12.35 ± 1.32 µm, p < 0.05) in diabetic mice. Unexpectedly under diabetic conditions, the combined treatment with enalapril/empagliflozin had no effects on both afferent and efferent arteriole diameter change. Conclusion: SGLT2 inhibition, besides ACE inhibition, is an essential hemodynamic regulator of glomerular filtration during diabetes mellitus. Nevertheless, additional mechanisms—independent from hemodynamic regulation—are involved in the nephroprotective effects especially of the combination therapy and should be further explored in future studies.

Application of the Full-Width-at-Half-Maximum Image Segmentation Method to Analyse Retinal Vascular Changes in Patients with Diabetic Retinopathy.

This study used spectral domain optical coherence tomography (SD-OCT) and full-width-at-half-maximum image segmentation to investigate the morphological changes of retinal blood vessels in patients with diabetic retinopathy (DR). Seventy-five patients with type 2 diabetes mellitus (T2DM) without DR and 65 patients with DR were studied. Vascular images of superior temporal region B of the retina were obtained by SD-OCT. The edges of retinal vessels were identified by the full-width-at-half-maximum image segmentation method. The lumen diameter, wall thickness (WT), wall cross-sectional area (WCSA), and wall-to-lumen ratio (WLR) were investigated. We found that, compared with the no diabetic retinopathy (NDR) group, patients in the DR group had an increased retinal arteriolar lumen diameter (RALD), retinal arteriolar outer diameter (RAOD), and WT (128.80 μm versus 104.88 μm; 147.01 μm versus 135.60 μm; 18.29 μm versus 15.26 μm, P < 0.05, respectively). The retinal venular lumen diameter (RVLD), retinal venular outer diameter (RVOD), and venular WT in the DR group were also increased (146.17 μm versus 133.66 μm; 180.20 μm versus 156.43 μm; 17.01 μm versus 11.38 μm, P < 0.05, respectively). The morphological changes in retinal vessels were significantly correlated with DR stage. In conclusion, in diabetic patients with DR, both retinal arteries and veins are widened and exhibit increased vascular thickness.

Blockade of endothelial Mas receptor restores the vasomotor response to phenylephrine in human resistance arterioles pretreated with captopril and exposed to propofol

BackgroundHypotension that is resistant to phenylephrine is a complication that occurs in anesthetized patients treated with angiotensin converting enzyme (ACE) inhibitors. We tested the hypothesis that Ang 1–7 and the endothelial Mas receptor contribute to vasodilation produced by propofol in the presence of captopril.MethodsThe internal diameters of human adipose resistance arterioles were measured before and after administration of phenylephrine (10–9 to 10–5 M) in the presence and absence of propofol (10–6 M; added 10 min before the phenylephrine) or the Mas receptor antagonist A779 (10–5 M; added 30 min before phenylephrine) in separate experimental groups. Additional groups of arterioles were incubated for 16 to 20 h with captopril (10–2 M) or Ang 1–7 (10–9 M) before experimentation with phenylephrine, propofol, and A779.ResultsPropofol blunted phenylephrine-induced vasoconstriction in normal vessels. Captopril pretreatment alone did not affect vasoconstriction, but the addition of propofol markedly attenuated the vasomotor response to phenylephrine. A779 alone did not affect vasoconstriction in normal vessels, but it restored vasoreactivity in arterioles pretreated with captopril and exposed to propofol. Ang 1–7 reduced the vasoconstriction in response to phenylephrine. Addition of propofol to Ang 1–7-pretreated vessels further depressed phenylephrine-induced vasoconstriction to an equivalent degree as the combination of captopril and propofol, but A779 partially reversed this effect.ConclusionsMas receptor activation by Ang 1–7 contributes to phenylephrine-resistant vasodilation in resistance arterioles pretreated with captopril and exposed to propofol. These data suggest an alternative mechanism by which refractory hypotension may occur in anesthetized patients treated with ACE inhibitors.

Lipoprotein Subclasses Independently Contribute to Subclinical Variance of Microvascular and Macrovascular Health.

Lipoproteins are important cardiovascular (CV) risk biomarkers. This study aimed to investigate the associations of lipoprotein subclasses with micro- and macrovascular biomarkers to better understand how these subclasses relate to atherosclerotic CV diseases. One hundred and fifty-eight serum samples from the EXAMIN AGE study, consisting of healthy individuals and CV risk patients, were analysed with nuclear magnetic resonance (NMR) spectroscopy to quantify lipoprotein subclasses. Microvascular health was quantified by measuring retinal arteriolar and venular diameters. Macrovascular health was quantified by measuring carotid-to-femoral pulse wave velocity (PWV). Nineteen lipoprotein subclasses showed statistically significant associations with retinal vessel diameters and nine with PWV. These lipoprotein subclasses together explained up to 26% of variation (R2 = 0.26, F(29,121) = 2.80, p < 0.001) in micro- and 12% (R2 = 0.12, F(29,124) = 1.70, p = 0.025) of variation in macrovascular health. High-density (HDL-C) and low-density lipoprotein cholesterol (LDL-C) as well as triglycerides together explained up to 13% (R2 = 0.13, F(3143) = 8.42, p < 0.001) of micro- and 8% (R2 = 0.08, F(3145) = 5.46, p = 0.001) of macrovascular variation. Lipoprotein subclasses seem to reflect micro- and macrovascular end organ damage more precisely as compared to only measuring HDL-C, LDL-C and triglycerides. Further studies are needed to analyse how the additional quantification of lipoprotein subclasses can improve CV risk stratification and CV disease prediction.

Analysis of Retinal Blood Vessel Diameters in Pregnant Women Practicing Yoga: A Feasibility Study.

Studies have shown that practicing yoga during pregnancy beneficially affects maternal and neonatal outcomes. The objective of this study was to determine the effect of prenatal yoga on the microvascular circulatory system via non-invasive measurements of retinal blood vessels. We included 29 women who practiced prenatal yoga in the study. There were no statistically significant differences in arteriolar and venular diameters pre- vs. post-90 min yoga practice (150.5 ± 11.4 μm pre- vs. 151.2 ± 10.2 μm post-yoga; p = 0.53 for arteriolar and 221.8 ± 16.1 μm pre- vs. 223.2 ± 15.7 μm post-yoga; p = 0.51 for venular diameters). The current study demonstrated the feasibility of the setup. More extensive studies are needed to determine the potential microvascular effects of practicing yoga throughout pregnancy.

In-vivo assessment of retinal vessel diameters and observer variability in mice: A methodological approach.

BackgroundCentral retinal arteriolar (CRAE) and venular (CRVE) diameter equivalents are predictive for cardiovascular and all-cause mortality in humans. The aim of this study was to investigate the inter- and intraobserver variability for the assessment of CRAE and CRVE in mice using fluorescein contrast enhancement as compared to crude analysis.MethodsThree high quality images with (F) and without fluorescein (NF) of eight mice (type C57BL) were recorded and analysed by two independent experienced investigators to investigate interobserver variability. In addition, one investigator analysed 20 F and 20 NF images twice to investigate intraobserver variability. The time course of CRAE and CRVE vessel responses after fluorescein injection were recorded in one mouse every 30 seconds for 15 minutes.ResultsThe interobserver variability was lower in F images compared to NF images for CRAE (r = 0.99, p < 0.001 vs. r = 0.65, p = 0.083) and CRVE (r = 0.99, p < 0.001 vs. r = 0.79, p = 0.019). Intraobserver variability for CRAE (r = 0.99, p < 0.001 vs. r = 0.48, p = 0.032) and CRVE (r = 0.98, p < 0.001 vs. r = 0.86, p < 0.001) were lower in F compared to NF images. Fluorescein injection induced vascular staining mimicking vessel dilation (+14%) followed by a long-lasting stable staining phase well suited for precise measurements.ConclusionsMeasurement variability can be optimized by use of fluorescein as contrast enhancement in mice. Standardization for time of image acquisition after fluorescein injection is advisable. Translation of static retinal vessel analysis into a rodent model has the potential to bridge the research gap between proof of concept studies in animals and clinical studies in humans.

Retinal microvascular associations with cardiometabolic risk factors differ by diabetes status: results from the UK Biobank

Aims/hypothesisThe aim of the study was to examine the association of retinal vessel morphometry with BP, body composition and biochemistry, and to determine whether these associations differ by diabetes status.MethodsThe UK Biobank ocular assessment included 68,550 participants aged 40-70 years who underwent non-mydriatic retinal photography, BP and body composition measurements, and haematological analysis. A fully automated image analysis program provided measurements of retinal vessel diameter and tortuosity. The associations between retinal vessel morphology and cardiometabolic risk factors by diabetes status were examined using multilevel linear regression, to provide absolute differences in vessel diameter and percentage differences in tortuosity (allowing for within-person clustering).ResultsA total of 50,233 participants (a reduction from 68,550) were included in these analyses. Overall, those with diabetes had significantly more tortuous venules and wider arteriolar diameters compared with those without. Associations between venular tortuosity and cardiometabolic risk factors differed according to diabetes status (p interaction <0.01) for total fat mass index, HbA1c, C-reactive protein, white cell count and granulocyte count. For example, a unit rise in white cell count was associated with a 0.18% increase (95% CI 0.05, 0.32%) in venular tortuosity for those without diabetes and a 1.48% increase (95% CI 0.90, 2.07%) among those with diabetes. For arteriolar diameter, significant interactions were evident for systolic BP, diastolic BP, mean arterial pressure (MAP) and LDL-cholesterol. For example, a 10 mmHg rise in systolic BP was associated with a −0.92 μm difference (95% CI −0.96 to −0.88 μm) in arteriolar diameter for those without diabetes, and a −0.58 μm difference (95% CI −0.76 to −0.41 μm) among those with diabetes. No interactions were observed for arteriolar tortuosity or venular diameters.Conclusions/interpretationWe provide clear evidence of the modifying effect of diabetes on cardiometabolic risk factor associations with retinal microvascular architecture. These observations suggest the occurrence of preclinical disease processes, and may be a sign of impaired autoregulation due to hyperglycaemia, which has been suggested to play a pivotal role in the development of diabetes-related microvascular complications.Data AvailabilityThe data supporting the results reported here are available through the UK Biobank (https://www.ukbiobank.ac.uk/enable-your-research/apply-for-access).Graphical abstract

A Review of the Methods of Non-Invasive Assessment of Intracranial Pressure through Ocular Measurement.

The monitoring of intracranial pressure (ICP) is essential for the detection and treatment of most craniocerebral diseases. Invasive methods are the most accurate approach to measure ICP; however, these methods are prone to complications and have a limited range of applications. Therefore, non-invasive ICP measurement is preferable in a range of scenarios. The current non-invasive ICP measurement methods comprise fluid dynamics, and ophthalmic, otic, electrophysiological, and other methods. This article reviews eight methods of non-invasive estimation of ICP from ocular measurements, namely optic nerve sheath diameter, flash visual evoked potentials, two-depth transorbital Doppler ultrasonography, central retinal venous pressure, optical coherence tomography, pupillometry, intraocular pressure measurement, and retinal arteriole and venule diameter ratio. We evaluated and presented the indications and main advantages and disadvantages of these methods. Although these methods cannot completely replace invasive measurement, for some specific situations and patients, non-invasive measurement of ICP still has great potential.

Critical Role of Neuronal Vps35 in Blood Vessel Branching and Maturation in Developing Mouse Brain.

Vps35 (vacuolar protein sorting 35), a key component of retromer, plays a crucial role in selective retrieval of transmembrane proteins from endosomes to trans-Golgi networks. Dysfunctional Vps35/retromer is a risk factor for the development of neurodegenerative diseases. Vps35 is highly expressed in developing pyramidal neurons, both in the mouse neocortex and hippocampus, Although embryonic neuronal Vps35’s function in promoting neuronal terminal differentiation and survival is evident, it remains unclear whether and how neuronal Vps35 communicates with other types of brain cells, such as blood vessels (BVs), which are essential for supplying nutrients to neurons. Dysfunctional BVs contribute to the pathogenesis of various neurodegenerative disorders. Here, we provide evidence for embryonic neuronal Vps35 as critical for BV branching and maturation in the developing mouse brain. Selectively knocking out (KO) Vps35 in mouse embryonic, not postnatal, neurons results in reductions in BV branching and density, arteriole diameter, and BV-associated pericytes and microglia but an increase in BV-associated reactive astrocytes. Deletion of microglia by PLX3397 enhances these BV deficits in mutant mice. These results reveal the function of neuronal Vps35 in neurovascular coupling in the developing mouse brain and implicate BV-associated microglia as underlying this event.

Alterations in ocular microcirculation and oxygen metabolism in patients with lipemia retinalis

PurposeThe study aims to assess the alterations in retinal oxygen saturation and retinal and choroidal blood flow in lipemia retinalis.MethodsThis was a cross-sectional study on 10 eyes (5 patients) with history of lipemia retinalis. The study comprised 10 eyes with documented history of lipemia retinalis and 10 participants as healthy controls. Patients with a confirmed history of lipemia retinalis were grouped into two cohorts based on their most recent fundus examination: untreated lipemia retinalis (abnormal fundus) and resolved lipemia retinalis (normal fundus). Both retinal arteriolar and venular oxygen saturation were measured using the non-invasive spectrophotometric retinal oximeter (Oxymap T1). The mean blur rate (MBR) of the optic nerve and choroidal blood flow were analyzed using a laser speckle flowgraph (LSFG).ResultsPatients with untreated lipemia retinalis had a significantly higher retinal arteriolar and venular oxygen saturation than that of the other two groups (p < 0.001). Moreover, patients with untreated lipemia retinalis had significantly smaller retinal arteriolar and venular diameters (p < 0.001). On LSFG, there was a significant difference in the overall MBR (p = 0.007) and vessel MBR of the optic nerve between the groups (p = 0.011). The patients with history of lipemia retinalis (untreated and resolved) exhibited a high overall MBR and vessel MBR of the optic nerve than that of the control group. There was a significant elevation of the optic nerve (p = 0.002) and choroidal blowout score (p < 0.001), while the resistivity index of the optic nerve (p = 0.001) and choroids (p = 0.002) was significantly lower in patients with resolved and untreated lipemia retinalis.ConclusionsThere was a significant alteration in retinal oximetry, in untreated lipemia retinalis, and in retinal blood flow, in both the resolved and untreated groups. The increase in retinal blood flow and oxygen saturation may elucidate the preservation of visual acuity and function despite the fundus changes observed in lipemia retinalis.

Association Between the Metabolic Syndrome and Retinal Microvascular Diameters Among Police Officers.

We examined the associations of the metabolic syndrome severity score (MSSS) and the metabolic syndrome (MetSyn) components with central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE). Participants in this cross-sectional study were 253 officers from the Buffalo Cardio-Metabolic Occupational Police Stress study (2011-2014). The MSSS is a z -score that represents the severity of MetSyn and was estimated using a sex/race-specific equation and the five MetSyn components. Associations of MSSS and the MetSyn with CRAE/CRVE were obtained using linear regression models or analysis of covariance. For every 1-standard deviation of MSSS, CRAE decreased by 2.3 μm (SE = 1.2, P = 0.0262) and CRVE increased by 3.4 μm (SE = 1.6, P = 0.0308) after adjusting for confounders. Officers with higher MSSS had narrower (ie, worse) arteriolar diameters and wider (ie, worse) venular diameters.