Increased Myocardial MAO-A, Atrogin-1, and IL-1ß Expression in Transgenic Mice with Pancreatic Carcinoma-Benefit of MAO-A Inhibition for Cardiac Cachexia.

Cancer cachexia (CC) continues to challenge clinicians by massively impairing patients' prognosis, mobility, and quality of life through skeletal muscle wasting. CC also includes cardiac cachexia as characterized by atrophy, compromised metabolism, innervation and function of the myocardium through factors awaiting clarification for therapeutic targeting. Because monoamine oxidase-A (MAO-A) is a myocardial source of H2O2 and implicated in myofibrillar protein catabolism and heart failure, we presently studied myocardial MAO-A expression, inflammatory cells, and capillarization together with transcripts of pro-inflammatory, -angiogenic, -apoptotic, and -proteolytic signals (by qRT-PCR) in a 3x-transgenic (LSL-KrasG12D/+; LSL-TrP53R172H/+; Pdx1-Cre) mouse model of orthotopic pancreatic ductal adenoarcinoma (PDAC) compared to wild-type (WT) mice. Moreover, we evaluated the effect of MAO-A inhibition by application of harmine hydrochloride (HH, 8 weeks, i.p., no sham control) on PDAC-related myocardial alterations. Myocardial MAO-A protein content was significantly increased (1.69-fold) in PDAC compared to WT mice. PDAC was associated with an increased percentage of atrogin-1+ (p < 0.001), IL-1ß+ (p < 0.01), COX2+ (p < 0.001), and CD68+ (p > 0.05) cells and enhanced transcripts of pro-inflammatory IL-1ß (2.47-fold), COX2 (1.53-fold), TNF (1.87-fold), and SOCS3 (1.64-fold). Moreover, PDAC was associated with a reduction in capillary density (-17%, p < 0.05) and transcripts of KDR (0.46-fold) but not of VEGFA, Notch1, or Notch3. Importantly, HH treatment largely reversed the PDAC-related increases in atrogin-1+, IL-1ß+, and TNF+ cell fraction as well as in COX2, IL-1ß, TNF, and SOCS3 transcripts, whereas capillary density and KDR transcripts failed to improve. In mice with PDAC, increased myocardial pro-atrophic/-inflammatory signals are attributable to increased expression of MAO-A, because they are significantly improved with MAO-A inhibition as a potential novel therapeutic option. The PDAC-related loss in myocardial capillary density may be due to other mechanisms awaiting evaluation with consideration of cardiomyocyte size, cardiac function and physical activity.

Superficial vessel density and determinants of macular microvasculature in healthy Chinese subjects.

BACKGROUND: The purpose of this study was to investigate the vessel density (VD) of the macular superficial capillary plexus (SCP) and its associated factors in healthy subjects. METHODS: This prospective, cross-sectional study enrolled healthy Chinese volunteers. The optical coherence tomography angiography (OCTA) was used to measure the superficial VD in macula. A generalized estimation equation (GEE) model was used to analyze the ocular and systemic associated factors. RESULTS: A total of 516 eyes of 262 healthy subjects were included (mean age 38.59 ± 21.03 years). The total VD of macular SCP was 16.85 ± 2.28 mm-1. The VD in the inner ring and outer ring were significantly higher than that in the central ring, with the density being highest in nasal quadrant and lowest in the superior quadrant. After adjusting the ocular and systemic factors, age (ß=-0.0085, P = 0.0122) and SSI (ß=1.3261, P < 0.001) were significantly associated with total VD of the macular SCP. CONCLUSIONS: Among the healthy Chinese subjects included in the study, the mean total VD of macular SCP was 16.85 ± 2.28mm-1. The macular superficial capillary density was positively associated with age and SSI. Further studies are still required to better understand the change of macular VD in aging and other pathological conditions.

Associations of retinal microvascular alterations with diabetes mellitus: an OCTA-based cross-sectional study.

BACKGROUND: Diabetes, a health crisis afflicting millions worldwide, is increasing rapidly in prevalence. The microvascular complications triggered by diabetes have emerged as the principal cause of renal disease and blindness. The retinal microvascular network may be sensitive to early systemic vascular structural and functional changes. Therefore, this research endeavored to discern the systemic determinants influencing the retinal microvascular network in patients with and without diabetes. METHODS: The Kailuan Eye Study is a cross-sectional study based on the community-based cohort Kailuan Study. Participants underwent optical coherence tomography angiography (OCTA) (Zeiss Cirrus 5000; Carl Zeiss Meditec) and comprehensive systemic examination. Metrics such as perfusion density (PD), vascular density (VD), foveal avascular zone (FAZ) parameters of the superficial capillary plexus (SCP) in the macula were assessed. RESULTS: This study included 860 eligible participants (average age = 62.75 ± 6.52 years; 21.9% female), of which 449 were diabetics. People with diabetes had diminished PD and VD in the entire macular and parafoveal regions compared to people without diabetes. Reduced PD in the whole macular region was correlated with higher fasting plasma glucose (FPG, mmol/L) concentration (Beta = -0.19, 95% CI = -0.42 to -0.36, P < 0.001), longer axial length (AL, mm) (Beta = -0.13, 95%CI = -0.48 to -0.25, P = 0.002), and elevated heart rate (Beta = -0.10, 95%CI = -0.14 to -0.19, P = 0.014), after adjusting for younger age (Beta = -0.18, 95%CI = -0.24 to -0.35, P < 0.001), consistent with VD of the whole macular region. A higher FPG level was significantly correlated with lower SCP density of both PD and VD in the macular and parafoveal region (P < 0.05 for all), as well as increased systolic blood pressure and low-density lipoprotein cholesterol concentration (P < 0.01 for all). CONCLUSIONS: In this large-sample cross-sectional study, OCTA evaluation revealed that high prevalence of diabetes and elevated FPG levels were correlated with reduced retinal VD and PD. Hypertension and hyperlipidemia are important risk factors for the development of atherosclerotic cardiovascular disease but have no significant effect on retinal microvascular abnormalities.

Nail fold capillaroscopy in leprosy: Unveiling the microvascular changes.

BACKGROUND: Leprosy, a chronic infectious disease, is associated with various nail changes. Its etiopathogenesis is multifaceted, with microvascular damage being crucial. Nail fold capillaroscopy (NFC) emerges as a novel tool for detecting early vascular deficits in leprosy. The study aimed to assess and provide a complete clinical characterization of NFC changes in leprosy patients. METHODS: It is an observational cross-sectional study, done over a period of 1.5 year (January 2021 to august 2022) in a tertiary care hospital, encompassing 60 patients diagnosed with leprosy (18-60 years). After obtaining informed consent; detailed history, complete cutaneous and neurological examinations were conducted. All fingernails and toenails were examined for clinical changes. Subsequently, onychoscopy was performed using USB type of video-dermatoscope (Model AM7115MZT Dino-lite), a non-invasive tool. This was followed by NFC which was done for all fingernails and images were recorded by single operator, which were then assessed for quantitative and qualitive changes and statistical analysis was conducted using SPSS v20, with mean capillary density compared using Student's t-test, morphological change frequencies assessed by proportions, and group comparisons made using Chi-square or Fischer exact tests, with a significance threshold of p < 0.05. RESULTS: Among the 60 patients, 39 were in the lepromatous group, which included both borderline lepromatous (BL) and lepromatous leprosy (LL) patients, and 17 were in the tuberculoid group, which included borderline tuberculoid (BT) leprosy patients; 23.3 % had Type 1 reactions, and 18.3 % had Type 2 reactions. Nail fold capillaroscopy (NFC) showed microvasculature changes in 93.3 % of patients. The average capillary density was 6.8 ± 1.5 capillaries per mm, with the lepromatous group having a lower density (6.5 ± 1.09) compared to the tuberculoid group (7.0 ± 0.86). The most common NFC changes in the tuberculoid group were tortuous capillaries (70 %), capillary dropouts, and dilated capillaries (both 64.7 %). In the lepromatous group, capillary dropouts (82 %) were most frequent, followed by tortuous (69 %), receding (69 %), and dilated capillaries (66 %). A dilated and prominent subpapillary plexus was more common in the lepromatous group (35 %, p = 0.04). Patients with trophic changes in the lepromatous group had more capillary dropouts and bizarre capillaries. Capillary dropouts, dilated capillaries, and visible subpapillary venous plexus were more prevalent in patients with Type 2 reactions. CONCLUSION: NFC changes are prevalent in both tuberculoid and lepromatous leprosy, which may be an indicator of peripheral vascular compromise and trophic changes, especially in lepromatous leprosy. NFC can be an auxiliary tool for detecting microvascular abnormalities in leprosy patients.

mTert induction in p21-positive cells counteracts capillary rarefaction and pulmonary emphysema.

Lung diseases develop when telomeres shorten beyond a critical point. We constructed a mouse model in which the catalytic subunit of telomerase (mTert), or its catalytically inactive form (mTertCI), is expressed from the p21Cdkn1a locus. Expression of either TERT or TERTCI reduces global p21 levels in the lungs of aged mice, highlighting TERT non-canonical function. However, only TERT reduces accumulation of very short telomeres, oxidative damage, endothelial cell (ECs) senescence and senile emphysema in aged mice. Single-cell analysis of the lung reveals that p21 (and hence TERT) is expressed mainly in the capillary ECs. We report that a fraction of capillary ECs marked by CD34 and endowed with proliferative capacity declines drastically with age, and this is counteracted by TERT but not TERTCI. Consistently, only TERT counteracts decline of capillary density. Natural aging effects are confirmed using the experimental model of emphysema induced by VEGFR2 inhibition and chronic hypoxia. We conclude that catalytically active TERT prevents exhaustion of the putative CD34 + EC progenitors with age, thus protecting against capillary vessel loss and pulmonary emphysema.

High-throughput Analysis of Capillary Density in Skeletal Muscle Cross Sections.

Capillary density in skeletal muscles is key to estimate exercise capacity in healthy individuals, athletes, and those with muscle-related pathologies. Here, we present a step-by-step, high-throughput semi-automated method for quantifying capillary density from whole human skeletal muscle cross-sections, in areas of the muscle occupied by myofibers. We provide a detailed protocol for immunofluorescence staining, image acquisition, processing, and quantification. Image processing is performed in ImageJ, and data analysis is conducted in R. The provided protocol allows high-throughput quantification of capillary density. Key features • This protocol builds upon the method and results described in Abbassi-Daloii et al. (2023b). • It includes step-by-step details on image acquisition and image processing of the entire muscle section. • It enables high-throughput and semi-automated image quantification of capillary density. • It provides a robust analysis for determining capillary density over the entire muscle cross section.

Type II Muscle Fiber Capillarization Is an Important Determinant of Post-Exercise Microvascular Perfusion in Older Adults.

INTRODUCTION: Microvascular perfusion is essential for post-exercise skeletal muscle recovery to ensure adequate delivery of nutrients and growth factors. This study assessed the relationship between various indices of muscle fiber capillarization and microvascular perfusion assessed by contrast-enhanced ultrasound (CEUS) at rest and during recovery from a bout of resistance exercise in older adults. METHODS: Sixteen older adults (72 ± 6 y, 5/11 male/female) participated in an experimental test day during which a muscle biopsy was collected from the vastus lateralis and microvascular perfusion was determined by CEUS at rest and at 10 and 40 min following a bout of resistance exercise. Immunohistochemistry was performed on muscle tissue samples to determine various indices of both mixed and fiber-type-specific muscle fiber capillarization. RESULTS: Microvascular blood volume at t = 10 min was higher compared with rest and t = 40 min (27.2 ± 4.7 vs. 3.9 ± 4.0 and 7.0 ± 4.9 AU, respectively, both p < 0.001). Microvascular blood volume at t = 40 min was higher compared with rest (p < 0.001). No associations were observed between different indices of mixed muscle fiber capillarization and microvascular blood volume at rest and following exercise. A moderate (r = 0.59, p < 0.05) and strong (r = 0.81, p < 0.001) correlation was observed between type II muscle fiber capillary-to-fiber ratio and the microvascular blood volume increase from rest to t = 10 and t = 40 min, respectively. In addition, type II muscle fiber capillary contacts and capillary-to-fiber perimeter exchange index were strongly correlated with the microvascular blood volume increase from rest to t = 40 min (r = 0.66, p < 0.01 and r = 0.64, p < 0.01, respectively). CONCLUSION: Resistance exercise strongly increases microvascular blood volume for at least 40 min after exercise cessation in older adults. This resistance exercise-induced increase in microvascular blood volume is strongly associated with type II muscle fiber capillarization in older adults.

Diagnostic performance of wide-field optical coherence tomography angiography in detecting open-angle glaucoma in high myopia.

PURPOSE: To compare the diagnostic performance of the capillary density (CD) of the central 1-6 mm and peripheral 6-12 mm annular regions in detecting open-angle glaucoma in high myopia (HM) using 15 × 12 mm wide-field swept-source optical coherence tomography angiography (WF SS-OCTA). METHODS: The study enrolled 206 and 103 eyes with HM and highly myopic open-angle glaucoma (HM-OAG), respectively. WF SS-OCTA images centred on the fovea were obtained to analyse the changes in the CD in the 1-3 mm, 3-6 mm, 6-9 mm, and 9-12 mm annular regions. CD of the superficial capillary plexus (SCP) was measured with the built-in software. The area under the receiver operating characteristic curve (AUROC) of each region was compared. RESULTS: The diagnostic performance of the SCP CD in the central 1-6 mm annular region (AUROC = 0.849) was better than that in the peripheral 6-12 mm annular region (AUROC = 0.756, p = 0.001). The annular AUROCs of SCP CD peaked in the 3-6 mm annular region (AUROC = 0.858) and gradually decreased with increasing diameter and were lower than the corresponding AUROCs of the ganglion cell-inner plexiform layer thickness (p < 0.05 for all comparisons). SCP CD of the inferior quadrant in the 3-6 mm annular region had the best diagnostic performance (AUROC = 0.859). CONCLUSION: The SCP CD in the central 1-6 mm annular region exhibited better diagnostic performance for the detection of HM-OAG in HM. The assessment of more peripheral regions has no added value in detecting glaucoma in HM.

Male spiny frogs enter the underwater battlefield with loose skin exhibiting enhanced penetration of capillaries into the epidermis.

The skin has multiple functions, and capillaries can penetrate the epidermis to shorten the diffusion path while allowing maintenance of overall epidermal thickness for nonrespiratory roles. However, a method for quantifying the capillary penetration extent is lacking. Such a method may facilitate making comparisons and detecting associations, potentially making the extent a useful variable in biological studies. We quantified the extent as the ratio of the average minimum thickness of epidermis overlying each capillary to the average epidermal thickness along a skin section and then explored its performance in the Emei mustache toad, Leptobrachium boringii, a species in which breeding males with loose skin call and fight each other with maxillary spines underwater. The ratio showed informative associations with other variables, such as perfused capillary density. It displayed small intragroup variation and could be more sensitive than other variables in revealing structural differences in the skin. The ratio estimates were lowest and were correlated with epidermal and stratum compactum thicknesses in breeding males, i.e., a covariation but not reinforcement against stabbing, constituting early evidence consistent with the increased extensibility of loose skin conferring a defensive advantage during combat in amphibians. In addition, our results lead to the hypothesis that high hemoglobin density along subepidermal capillaries favors the maintenance of low blood partial oxygen pressure and hence increases cutaneous oxygen uptake. We also provide evidence supporting the new idea that the cooccurrence of loose skin and underwater calling found in some frogs can be explained by the latter benefiting from a large functional respiratory surface area. Awareness of the usefulness of the ratio may promote its application and the quantification of the penetration. Regarding exchange surface design, these findings for L. boringii imply a case in which looseness increases surface area as well as prevents damage.

Combining retinal structural and vascular measurements improves discriminative power for multiple sclerosis patients.

Data on how retinal structural and vascular parameters jointly influence the diagnostic performance of detection of multiple sclerosis (MS) patients without optic neuritis (MSNON) are lacking. To investigate the diagnostic performance of structural and vascular changes to detect MSNON from controls, we performed a cross-sectional study of 76 eyes from 51 MS participants and 117 eyes from 71 healthy controls. Retinal macular ganglion cell complex (GCC), retinal nerve fiber layer (RNFL) thicknesses, and capillary densities from the superficial (SCP) and deep capillary plexuses (DCP) were obtained from the Cirrus AngioPlex. The best structural parameter for detecting MS was compensated RNFL from the optic nerve head (AUC = 0.85), followed by GCC from the macula (AUC = 0.79), while the best vascular parameter was the SCP (AUC = 0.66). Combining structural and vascular parameters improved the diagnostic performance for MS detection (AUC = 0.90; p<0.001). Including both structure and vasculature in the joint model considerably improved the discrimination between MSNON and normal controls compared to each parameter separately (p = 0.027). Combining optical coherence tomography (OCT)-derived structural metrics and vascular measurements from optical coherence tomography angiography (OCTA) improved the detection of MSNON. Further studies may be warranted to evaluate the clinical utility of OCT and OCTA parameters in the prediction of disease progression.

Automated nailfold capillary density measurement method based on improved YOLOv5.

Nailfold capillary density is an essential physiological parameter for analyzing nailfold health; however, clinical images of the nailfold are taken in many situations, and most clinicians subjectively analyze nailfold images. Therefore, based on the improved "you only look once v5" (YOLOv5) algorithm, this study proposes an automated method for measuring nailfold capillary density. The improved technique can effectively and rapidly detect distal capillaries by incorporating methods or structures such as 9mosaic, spatial pyramid pooling cross-stage partial construction, bilinear interpolation, and efficient intersection over union. First, the modified YOLOv5 algorithm was used to detect nailfold capillaries. Subsequently, the number of distal capillaries was filtered using the 90° method. Finally, the capillary density was calculated. The results showed that the Average Precision (AP)@0.5 value of the proposed approach reached 85.2 %, which was an improvement of 4.93 %, 5.24 %, and 107 % compared with the original YOLOv5, YOLOv6, and simple-faster rapid-region convolutional network (R-CNN), respectively. For different nailfold images, using the density calculated by nailfold experts as a benchmark, the calculated results of the proposed method were consistent with the manually calculated results and superior to those of the original YOLOv5.

Correlations between capillary density and degree of skin pigmentation in healthy children analysed by nailfold video capillaroscopy.

Background: Nailfold video capillaroscopy (NVC) is a simple, non-invasive diagnostic tool but studies with normal values for capillary density in healthy children are rare. Ethnic background seems to play a role in capillary density; however, this is not well substantiated yet. In this work, we set out to evaluate influence of ethnic background/skin pigmentation and age on capillary density reading in healthy children. Secondary aim was to investigate whether there is a significant difference in density between different fingers within the same patient. Methods: Between 2016 and 2021, healthy children from schools around AUMC were approached, by convenience sampling. In this cross-sectional study, capillaroscopic images were obtained in a one-time videocapillaroscopy (×200 magnification) addressing the capillary density (i.e., number of capillaries per linear millimetre in the distal row). This parameter was compared to age, sex, ethnicity, skin pigment grade (I-III) and between eight different fingers, excluding the thumbs. Density differences were compared by ANOVAs. Correlations between capillary density and age were calculated with Pearson correlations. Results: We investigated 145 healthy children with mean age of 11.03 years (SD 3.51). The range of capillary density was 4-11 capillaries per millimetre. We observed a lower capillary density in the 'grade II' (6.4±0.5 cap/mm, P<0.001) and 'grade III' (5.9±0.8 cap/mm, P<0.001) pigmented-classified groups compared to the 'grade I' group (7.0±0.7 cap/mm). We did not find a significant correlation between age and density in the overall group. The fifth fingers on both sides had a significantly lower density compared to the other fingers. Conclusions: Healthy children <18 years with higher degree of skin pigmentation show a significantly lower nailfold capillary density. In subjects with an African/Afro-Caribbean and North-African/Middle-Eastern ethnicity, a significantly lower mean capillary density was observed compared to subjects with the Caucasian ethnicity (P<0.001, and P<0.05, respectively. There were no significant differences between other ethnicities. No correlation was found between age and capillary density. The fifth fingers on both hands displayed lower capillary density compared to the other fingers. This needs to be taken into account when describing lower density in paediatric patients with connective tissue diseases.

Increased peripapillary capillaries in patients with acute leukemia by using optical coherence tomography angiography.

PURPOSE: To evaluate the radial peripapillary capillary vessel density (RPC-VD) and thickness of the retinal nerve fiber layer (RNFL) in acute leukemia (AL) and the associations of these characteristics with blood laboratory parameters. METHODS: A cross-sectional study was performed at the Ophthalmology Department of the Sun Yat-sen Memorial Hospital from February 2019 to April 2022. Sixty eyes of 30 patients diagnosed with AL and sixty eyes of 30 matched healthy controls were included. Optical coherence tomography angiography (OCTA) in the 4.5-mm Angio Disc scan mode and the Ganglion cell complex scan mode were performed for all participants. Correlation analyses were used to examine the associations of RPC-VD and RNFL with blood laboratory parameters. RESULTS: Patients in the AL group had significantly increased RPC-VD in the whole-image (51.42±0.35 vs. 49.52±0.36) and peripapillary fields (53.90±0.43 vs. 51.17±0.50) compared with people in the control group (all P<0.001), while no difference was found for RPC-VD in the inside optic disk fields in the two groups. The RNFL in the AL group was significantly thicker than that in the control group (131.10±3.89 µm vs. 115.03±2.22 µm, P<0.05). Complete blood count (CBC) parameters, including red blood cells, hemoglobin and hematocrit, had a significant negative correlation with RPC-VD and RNFL (all P <0.05). CONCLUSION: An increased RPC-VD and a thicker RNFL are evidence of fundus changes in patients with early-stage AL, and these metrics may be related to decreases in red blood cells, hemoglobin and hematocrit.

Microcirculatory changes as a hallmark of aging in the heart and kidney / Cambios microcirculatorios como sello distintivo del envejecimiento en el corazón y riñón

SUMMARY: Changes in the microcirculation of multiple tissues and organs have been implicated as a possible mechanism in physiological aging. In particular, vascular endothelial growth factor is a secretory protein responsible for regulating angiogenesis via altering endothelial proliferation, survival, migration, extracellular matrix degradation and cell permeability. The aim of the present study was to evaluate the role of vascular endothelial growth factor in the progression of morphological alterations caused by physiological aging in the heart and kidney and to examine its relation to changes in capillary density. We used two age groups of healthy Wistar rats - 6- and 12-month- old. The expression of vascular endothelial growth factor was examined through immunohistochemistry and immunofluorescence and assessed semi-quantitatively. Changes in capillary density were evaluated statistically and correlated with the expression of vascular endothelial growth factor. We reported stronger immunoreactivity for vascular endothelial growth factor in the left compared to the right ventricle and also observed an increase in its expression in both ventricles in older animals. Contrasting results were reported for the renal cortex and medulla. Capillary density decreased statistically in all examined structures as aging progressed. The studied correlations were statistically significant in the two ventricles in 12-month-old animals and in the renal cortex of both age groups. Our results shed light on some changes in the microcirculation that take place as aging advances and likely contribute to impairment in the function of the examined organs.

Los cambios en la microcirculación de múltiples tejidos y órganos se han implicado como un posible mecanismo en el envejecimiento fisiológico. En particular, el factor de crecimiento endotelial vascular es una proteína secretora responsable de regular la angiogénesis mediante la alteración de la proliferación endotelial, la supervivencia, la migración, la degradación de la matriz extracelular y la permeabilidad celular. El objetivo del presente estudio fue evaluar el papel del factor de crecimiento del endotelio vascular en la progresión de las alteraciones morfológicas causadas por el envejecimiento fisiológico en el corazón y riñón y examinar su relación con los cambios en la densidad capilar. Utilizamos dos grupos de ratas Wistar sanas: 6 y 12 meses de edad. La expresión del factor de crecimiento del endotelio vascular se examinó mediante inmunohistoquímica e inmunofluorescencia y se evaluó semicuantitativamente. Los cambios en la densidad capilar se evaluaron estadísticamente y se correlacionaron con la expresión del factor de crecimiento del endotelio vascular. Informamos una inmunorreactividad más fuerte para el factor de crecimiento endotelial vascular en el ventrículo izquierdo en comparación con el derecho y también observamos un aumento en su expresión en ambos ventrículos en animales mayores. Se informaron resultados contrastantes para la corteza renal y la médula. La densidad capilar disminuyó estadísticamente en todas las estructuras examinadas a medida que avanzaba el envejecimiento. Las correlaciones estudiadas fueron estadísticamente significativas en los dos ventrículos en animales de 12 meses y en la corteza renal de ambos grupos de edad. Nuestros resultados arrojan luz sobre algunos cambios en la microcirculación que tienen lugar a medida que avanza el envejecimiento y probablemente contribuyan a un deterioro en la función de los órganos examinados.

Peripapillary microvasculature changes after vitrectomy in epiretinal membrane via swept-source OCT angiography.

PURPOSE: To evaluate the peripapillary microvasculature changes in patients with epiretinal membrane (ERM) following pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling using swept-source optical coherence tomography angiography (SS-OCTA). METHOD: Medical records and multimodal imaging data of 33 eyes after PPV for ERM were retrospectively reviewed. Peripapillary SS-OCTA images of 6×6 mm2 were recorded at at pre- and post-operatively every 6 months for 1 year. A semi-automated method was used to analyzed SS-OCTA images, excluding the optic disc area, using the MATLAB software. The peripapillary vessel density (pVD) of superficial capillary plexus (SCP) and deep capillary plexus (DCP) was quantified in four quadrants (superior, inferior, nasal and temporal). RESULT: The mean pVD in SCP and DCP decreased at 6- and 12-months follow-up. In sectoral analysis, superior, inferior, and temporal quadrants pVD in SCP and DCP were significantly reduced at 1 year after vitrectomy (all p < 0.05). Meanwhile, inferior quadrants pVD in SCP and DCP showed the earliest significant reduction at 6-months (p = 0.022 and 0.048, respectively). A reduction of post-operative mean pVD in DCP was significantly greater in patients with diabetic retinopathy (p = 0.043). CONCLUSION: Peripapillary capillary density significantly decreased after surgical removal of ERM. Vitrectomy with ILM peeling can cause peripapillary microvascular damage starting in inferior sector.

Age-related alterations in retinal capillary function.

PURPOSE: To determine age-related alterations in the retinal capillary function (RCF, the ability to transport blood flow) in healthy subjects. METHODS: A total of 148 healthy subjects (aged 18 to 83 years) were enrolled, and one eye of each subject was imaged. Retinal blood flow (RBF) was measured using a Retinal Function Imager, and retinal capillary density (RCD, expressed as fractal dimension Dbox) was measured using optical coherence tomography angiography. RCF was defined as the ratio of RBF to RCD, representing the ability to transport blood flow. The relationship between RCF and age was analyzed. In addition, the cohort was divided into four groups (G1, <35 years, G2, 35-49 years, G3, 50-64 years, and G4, ≥65 years) for further analysis. RESULTS: With all data, the relation between the RCF and age had a trend of a quadratic model (G1-4: r = 0.16, P = 0.14). After 35 years (i.e., G2-4), the relation had a trend between the RCF and age fitted into a negative linear model (r = -0.23, P = 0.05). Moreover, after 50 years (i.e., G3-4), the negative linear model became stronger (r = -0.37, P = 0.03). The average RCF was 2.24 ± 0.22 µl/s/Dbox in G4, significantly lower than that in G2 (2.65 ± 0.56 µl/s/Dbox, P = 0.018) and G3 (2.64 ± 0.70 µl/s/Dbox, P = 0.034), but did not reach a significant level compared to that in G1 (2.55 + 0.51 µl/s/Dbox, P = 0.056). CONCLUSIONS: This is the first study to determine age-related alterations in the RCF in a healthy population. Decreased RCF in the older group may represent a characteristic pattern of normal aging.

Assessment of peritubular capillary rarefaction in kidneys of cats with chronic kidney disease.

BACKGROUND: Hypoxia is a key driver of fibrosis and is associated with capillary rarefaction in humans. OBJECTIVES: Characterize capillary rarefaction in cats with chronic kidney disease (CKD). ANIMALS: Archival kidney tissue from 58 cats with CKD, 20 unaffected cats. METHODS: Cross-sectional study of paraffin-embedded kidney tissue utilizing CD31 immunohistochemistry to highlight vascular structures. Consecutive high-power fields from the cortex (10) and corticomedullary junction (5) were digitally photographed. An observer counted and colored the capillary area. Image analysis was used to determine the capillary number, average capillary size, and average percent capillary area in the cortex and corticomedullary junction. Histologic scoring was performed by a pathologist masked to clinical data. RESULTS: Percent capillary area (cortex) was significantly lower in CKD (median 3.2, range, 0.8-5.6) compared to unaffected cats (4.4, 1.8-7.0; P = <.001) and was negatively correlated with serum creatinine concentrations (r = -.36, P = .0013), glomerulosclerosis (r = -0.39, P = <.001), inflammation (r = -.30, P = .009), and fibrosis (r = -.30, P = .007). Capillary size (cortex) was significantly lower in CKD cats (2591 pixels, 1184-7289) compared to unaffected cats (4523 pixels, 1801-7618; P = <.001) and was negatively correlated with serum creatinine concentrations (r = -.40, P = <.001), glomerulosclerosis (r = -.44, P < .001), inflammation (r = -.42, P = <.001), and fibrosis (r = -.38, P = <.001). CONCLUSIONS AND CLINICAL IMPORTANCE: Capillary rarefaction (decrease in capillary size and percent capillary area) is present in kidneys of cats with CKD and is positively correlated with renal dysfunction and histopathologic lesions.

Depletion of vascular adaptive mechanisms in hypertension-induced injury of the heart and kidney.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a signalling protein of critical importance for angiogenesis. In an effort to better understand its significance in hypertension-induced injury of the heart and kidney we aimed at studying the changes in its expression in an experimental model and correlated it with capillary density in the myocardium and the renal parenchyma. METHODS: We used two age groups of spontaneously hypertensive rats (6- and 12-month-old), indicative of early and advanced hypertension. VEGF expression was assessed and a semi-quantitative analysis of its immunoreactivity was conducted. Changes in capillary density in the myocardium and kidney were assessed for statistical significance and correlations with VEGF expression were established. RESULTS: We reported stronger VEGF expression in animals with early compared to advanced hypertension in all examined structures. Capillary density decreased significantly at age 12 months compared to 6 months and was significant in all examined structures. A positive correlation was established between capillary density and the expression of VEGF. CONCLUSION: These findings underscore the key significance of VEGF for compensatory angiogenesis and suggest that a statistically significant depletion of these vascular adaptive mechanisms is a major aspect in the cascade of hypertension-induced injury of the heart and kidney (Tab. 3, Fig. 26, Ref. 47).

Three-dimensional analyses of vascular network morphology in a murine lymph node by X-ray phase-contrast tomography with a 2D Talbot array.

With growing molecular evidence for correlations between spatial arrangement of blood vasculature and fundamental immunological functions, carried out in distinct compartments of the subdivided lymph node, there is an urgent need for three-dimensional models that can link these aspects. We reconstructed such models at a 1.84 µm resolution by the means of X-ray phase-contrast imaging with a 2D Talbot array in a short time without any staining. In addition reconstructions are verified in immunohistochemistry staining as well as in ultrastructural analyses. While conventional illustrations of mammalian lymph nodes depict the hilus as a definite point of blood and lymphatic vessel entry and exit, our method revealed that multiple branches enter and emerge from an area that extends up to one third of the organ's surface. This could be a prerequisite for the drastic and location-dependent remodeling of vascularization, which is necessary for lymph node expansion during inflammation. Contrary to corrosion cast studies we identified B-cell follicles exhibiting a two times denser capillary network than the deep cortical units of the T-cell zone. In addition to our observation of high endothelial venules spatially surrounding the follicles, this suggests a direct connection between morphology and B-cell homing. Our findings will deepen the understanding of functional lymph node composition and lymphocyte migration on a fundamental basis.