Retinal Vascular System Research Articles

Cu-Doping Layered Double Hydroxides Nanozyme Integrated with Nitric Oxide Donor for Enhanced Antioxidant Therapy in Retinopathy.

The prevalence of retinal neovascular diseases necessitates novel treatments beyond current therapies like laser surgery or anti-VEGF treatments, which often carry significant side effects. A novel therapeutic approach is introduced using copper-containing layered double hydroxides (Cu-LDH) nanozymes integrated with nitric oxide-releasing molecules (GSHNO), forming Cu-LDH@GSHNO aimed at combating oxidative stress within the retinal vascular system. Combination of synthetic chemistry and biological testing, Cu-LDH@GSHNO are synthesized, characterized, and assessed for curative effect in HUVECs and an oxygen-induced retinopathy (OIR) mouse model. The results indicate that Cu-LDH@GSHNO demonstrates SOD-CAT cascade catalytic ability, accompanied with GSH and nitric oxide-releasing capabilities, which significantly reduces oxidative cell damage and restores vascular function, presenting a dual-function strategy that enhances treatment efficacy and safety for retinal vascular diseases. The findings encourage further development and clinical exploration of nanozyme-based therapies, promising a new horizon in therapeutic approaches for managing retinal diseases driven by oxidative stress.

Retinal Hemorrhages in a Newborn with Prenatal Cocaine Exposure

A term male newborn small for gestational age and with microcephaly was born from uncomplicated vaginal delivery. Pregnancy was not followed up until 32 weeks. Maternal serologies and vaginal/rectal swabs were negative. Routine ophthalmoscopy revealed hemovitreous in the right eye and massive retinal hemorrhages (RH) in the left eye; subsequent RetCam II examination with fluorescein angiography revealed bilateral RH, involving the fovea in the left eye. Retinal vascularization was normal in both eyes, without signs of ischemic injury or pathological angiogenesis. Complete blood count, coagulation, and thrombophilic studies were normal; a toxicology screen, performed on a hair sample from both mother and infant, was positive for cocaine. With its significant vasoconstrictive effects, cocaine may induce ischemic-hypoxic damage in the developing retinal vascular system of the fetus, leading to extensive RH. Although cocaine-related RH is indistinguishable from other birth-related RH, the formers persist for longer periods, warranting prolonged follow-up and long-term evaluation of visual function.

Segmentation of Low-Light Optical Coherence Tomography Angiography Images under the Constraints of Vascular Network Topology.

Optical coherence tomography angiography (OCTA) offers critical insights into the retinal vascular system, yet its full potential is hindered by challenges in precise image segmentation. Current methodologies struggle with imaging artifacts and clarity issues, particularly under low-light conditions and when using various high-speed CMOS sensors. These challenges are particularly pronounced when diagnosing and classifying diseases such as branch vein occlusion (BVO). To address these issues, we have developed a novel network based on topological structure generation, which transitions from superficial to deep retinal layers to enhance OCTA segmentation accuracy. Our approach not only demonstrates improved performance through qualitative visual comparisons and quantitative metric analyses but also effectively mitigates artifacts caused by low-light OCTA, resulting in reduced noise and enhanced clarity of the images. Furthermore, our system introduces a structured methodology for classifying BVO diseases, bridging a critical gap in this field. The primary aim of these advancements is to elevate the quality of OCTA images and bolster the reliability of their segmentation. Initial evaluations suggest that our method holds promise for establishing robust, fine-grained standards in OCTA vascular segmentation and analysis.

Conditional loss of Ube3d in the retinal pigment epithelium accelerates age-associated alterations in the retina of mice.

Several studies have suggested a correlation between the ubiquitin-proteasome system (UPS) and age-related macular degeneration (AMD), with its phenotypic severity ranging from mild visual impairment to blindness, but the mechanism for UPS dysfunction contributing to disease progression is unclear. In this study, we investigated the role of ubiquitin protein ligase E3D (UBE3D) in aging and degeneration in mouse retina. Conditional knockout of Ube3d in the retinal pigment epithelium (RPE) of mice led to progressive and irregular fundus lesions, attenuation of the retinal vascular system, and age-associated deterioration of rod and cone responses. Simultaneously, RPE-specific Ube3d knockout mice also presented morphological changes similar to the histopathological characteristics of human AMD, in which a defective UPS led to RPE abnormalities such as phagocytosis or degradation of metabolites, the interaction with photoreceptor outer segment, and the transport of nutrients or waste products with choroidal capillaries via Bruch's membrane. Moreover, conditional loss of Ube3d resulted in aberrant molecular characterizations associated with the autophagy-lysosomal pathway, oxidative stress damage, and cell-cycle regulation, which are implicated in AMD pathology. Thus, our findings strengthen and expand the impact of UPS dysfunction on retinal pathophysiology during aging, indicating that genetic Ube3d deficiency in the RPE could lead to the abnormal formation of pigment deposits and secondary fundus alterations. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Senescent Cells: Dual Implications on the Retinal Vascular System.

Cellular senescence, a state of permanent cell cycle arrest in response to endogenous and exogenous stimuli, triggers a series of gradual alterations in structure, metabolism, and function, as well as inflammatory gene expression that nurtures a low-grade proinflammatory milieu in human tissue. A growing body of evidence indicates an accumulation of senescent neurons and blood vessels in response to stress and aging in the retina. Prolonged accumulation of senescent cells and long-term activation of stress signaling responses may lead to multiple chronic diseases, tissue dysfunction, and age-related pathologies by exposing neighboring cells to the heightened pathological senescence-associated secretory phenotype (SASP). However, the ultimate impacts of cellular senescence on the retinal vasculopathies and retinal vascular development remain ill-defined. In this review, we first summarize the molecular players and fundamental mechanisms driving cellular senescence, as well as the beneficial implications of senescent cells in driving vital physiological processes such as embryogenesis, wound healing, and tissue regeneration. Then, the dual implications of senescent cells on the growth, hemostasis, and remodeling of retinal blood vessels are described to document how senescent cells contribute to both retinal vascular development and the severity of proliferative retinopathies. Finally, we discuss the two main senotherapeutic strategies-senolytics and senomorphics-that are being considered to safely interfere with the detrimental effects of cellular senescence.

Retinal microvasculature features in patients with migraine: a systematic review and meta-analysis.

Migraine is a central nervous system disorder involving neuronal and vascular factors. The brain has a close anatomical relationship with retinal vessels and similar regulatory processes, and the retinal vascular system is the only in vivo vessel that can be directly visualized, while optical coherence tomography angiography (OCTA) is an advanced retinal vascular imaging technique. In this study, OCTA was used to study the retinal vascular density (VD) and foveal avascular zone (FAZ) in migraine patients, which provided a theoretical basis for its use as a candidate for rapid and non-invasive diagnosis of migraine. Published studies comparing retinal microvascular profiles between migraine patients and healthy controls were obtained by a comprehensive search of electronic databases. Nine studies were finally included, including 775 eyes (migraine group: 444 eyes, control group: 331 eyes). Pooled effect sizes were presented as standardized mean differences (SMDs) and 95% confidence intervals (CIs). Statistical analysis was performed using Review Manager software (version 5.30). The combined results revealed that the superficial and deep macular whole enface VD (MWEVD) (superficial VD: SMD = -0.30, P = 0.0001; deep VD: SMD = -0.61, P = 0.02), superficial foveal VD (FVD) (SMD = -0.42, P = 0.03), deep parafoveal VD (PFVD) (SMD = -0.31, P = 0.002), and peripapillary VD (PVD) (SMD = -0.49, P = 0.002) were significantly reduced in migraine patients compared with healthy people. However, there was a significant increase in the area of the FAZ in migraine patients (SMD = 0.56, P < 0.0001). Migraine patients are prone to retinal microcirculation disorders, such as decreased blood vessel density and increased avascular area in the fovea. This provides a theoretical basis for OCTA as a candidate for rapid, non-invasive diagnosis of migraine.

Acrolein Induces Retinal Abnormalities of Alzheimer's Disease in Mice.

It is reported that retinal abnormities are related to Alzheimer's disease (AD) in patients and animal models. However, it is unclear whether the retinal abnormities appear in the mouse model of sporadic Alzheimer's disease (sAD) induced by acrolein. We investigated the alterations of retinal function and structure, the levels of β-amyloid (Aβ) and phosphorylated Tau (p-Tau) in the retina, and the changes in the retinal vascular system in this mouse model. We demonstrated that the levels of Aβ and p-Tau were increased in the retinas of mice from the acrolein groups. Subsequently, a decreased amplitudes of b-waves in the scotopic and photopic electroretinogram (ERG), decreased thicknesses of the retinal nerve fiber layer (RNFL) in the retina, and slight retinal venous beading were found in the mice induced by acrolein. We propose that sAD mice induced by acrolein showed abnormalities in the retina, which may provide a valuable reference for the study of the retina in sAD.

Effects of Sinovac-Coronavac and Pfizer-BioNTech mRNA vaccines on choroidal and retinal vascular system

PurposeTo evaluate the effects of Sinovac-Coronavac and Pfizer-BioNTech mRNA vaccines on choroidal and retinal vascular system using enhanced depth imaging optical coherence tomography (EDI-OCT) and optical coherence tomography angiography (OCTA). MethodsIn this prospective cross-sectional study, 63 healthy participants (29 with Pfizer-BioNTech, 34 with Sinovac-CoronaVac) were evaluated after the first dose of vaccination. Vessel density (VD) of the superficial (SCP), deep capillary plexus (DCP) and choriocapillaris (CC) were measured with OCTA. Choroidal thickness (CT) were measured with EDI-OCT. Measurements were performed at the 2nd week and the 4th week after vaccinations and compared to pre-vaccination values. ResultsRegarding Pfizer-BioNTech vaccination, CT in the subfoveal and nasal region significantly increased between the pre-vaccination and post-vaccination 2nd week and then significantly decreased to pre-vaccine values at 4th week. The SCP-VD (whole image, fovea, parafovea, perifovea temporal) variables showed a significant decrease at 2nd week. The DCP-VD inferior hemi, parafovea inferior hemi, parafovea inferior variables demonstrated a significant decrease at 2nd week. The perifovea DCP-VD variables also showed a significant decrease at 2nd week, and these variables returned to pre-vaccination values after 4 weeks. The CC-VD variables showed a significant decrease between pre-vaccine and 2nd week post-vaccination. Regarding the Sinovac-CoronaVac vaccination, there was no statistically significant difference in CT and VD values before and after vaccination (p> 0.05). ConclusionOur study showed significant alterations in retinal vascular density and CT for the Pfizer-BioNTech vaccine at the 2nd week, and these parameters became compatible with pre-vaccination values at the 4th week. In contrast, no differences were observed after the Sinovac-Coronovac vaccination.

Optical coherence tomography angiography: a review of the current literature

This narrative review presents a comprehensive examination of optical coherence tomography angiography (OCTA), a non-invasive retinal vascular imaging technology, as reported in the existing literature. Building on the coherence tomography principles of standard OCT, OCTA further delineates the retinal vascular system, thus offering an advanced alternative to conventional dye-based imaging. OCTA provides high-resolution visualisation of both the superficial and deep capillary networks, an achievement previously unattainable. However, image quality may be compromised by factors such as motion artefacts or media opacities, potentially limiting the utility of OCTA in certain patient cohorts. Despite these limitations, OCTA has various potential clinical applications in managing retinal and choroidal vascular diseases. Still, given its considerable cost implications relative to current modalities, further research is warranted to justify its broader application in clinical practice.

Impact of Microgravity and Other Spaceflight Factors on Retina of Vertebrates and Humans In Vivo and In Vitro.

Spaceflight (SF) increases the risk of developmental, regenerative, and physiological disorders in animals and humans. Astronauts, besides bone loss, muscle atrophy, and cardiovascular and immune system alterations, undergo ocular disorders affecting posterior eye tissues, including the retina. Few studies revealed abnormalities in the development and changes in the regeneration of eye tissues in lower vertebrates after SF and simulated microgravity. Under microgravity conditions, mammals show disturbances in the retinal vascular system and increased risk of oxidative stress that can lead to cell death in the retina. Animal studies provided evidence of gene expression changes associated with cellular stress, inflammation, and aberrant signaling pathways. Experiments using retinal cells in microgravity-modeling systems in vitro additionally indicated micro-g-induced changes at the molecular level. Here, we provide an overview of the literature and the authors' own data to assess the predictive value of structural and functional alterations for developing countermeasures and mitigating the SF effects on the human retina. Further emphasis is given to the importance of animal studies on the retina and other eye tissues in vivo and retinal cells in vitro aboard spacecraft for understanding alterations in the vertebrate visual system in response to stress caused by gravity variations.

Уникальный патологический и физиологический ангиогенез ретинопатии недоношенных в аспектах безопасности селективной анти-VEGF терапии

ROP in the developing retina of premature infants is unique because of the coexistence of physiological and pathological angiogenesis. The type of structure of the vascular nodes is the way to understand the selective treatment of ROP. Purpose. Identification of criteria for the selective ROP treatment choice using the type of pathological vasculogenesis. Material and methods. The study included 279 patients with ROP – 1 group (stage I), 152 (304 eyes); group 2 (stage II) – 45 (90 eyes); 3 group (III stage) – 8 (12 eyes); group 4 (IVA stage) –7 (8 eyes); 5 group (posterior aggressive ROP) – 7 (14 eyes); group 6 (immature retina) 60 (120 eyes) – control; 231 (188 eyes) patients with ROP referred for surgical treatment, divided into subgroups before and after lasercoagulation of the retina. Fractal dimension (Df) and complexity of vascular system (СVS) on wide-field images were assessed. Results. In the group before treatment Df 1.4374 ± 0.03, CVS 2.8 ± 0.14, in the group after treatment Df 1.3756 ± 0.03, CVS 2.3 ± 0.21. According to the morphometric data of 12 images, Df (p = 0.004) and CCC (p = 0.02) values were statistically different in subgroups before and after treatment. Low values of Df (&lt; 1.34) may indicate a more pronounced shift of angiogenesis towards pathological, since normally Df of the formed vasculature is 1.7. In this case, it is preferable to use anti-VEGF therapy. Conclusion. The Df and CVS are indicators are relevant parameters for evaluating the effectiveness of laser treatment in patients with ROP. Vascular patterns are unique for each post-conceptual age, CVS and Df are potential markers of the balance between pathological and physiological angiogenesis for the selective choice of ROP therapy. Keywords: retinopathy of prematurity, retinal laser photocoagulation, retinal vascular system, antiVEGF

Microvasculature evaluation of anisometropic amblyopia children by Angio-OCT

To compare and assess the choroidal and retinal microstructural vascularity in amblyopic eyes with the fellow eyes in anisometropic amblyopic children using angiography optical coherence tomography (Angio-OCT). Twenty-seven children (54 eyes; 5.59 ± 1.08 years old; 59.3% girls) were enrolled in this study. Choroidal thickness (CT) was measured with the use of the enhanced depth imaging mode in Angio-OCT. Parafoveal/peripapillary vascular density indices and the foveal avascular zone (FAZ) size were analyzed by MATLAB code programming on Angio-OCT images. The mean FAZ size of the amblyopic eyes were larger both in superficial and deep capillary plexus layer (SCPL/DCPL). Compared with the contralateral eyes (BCVA were normal), all the vascular density indices of SCPL and DCPL in the parafoveal and peripapillary zones were lower in the amblyopic eyes, however, the difference was insignificant (p > 0.05). No significant decrease was observed in four quadrants analyses of the amblyopic eyes (p > 0.05). Except for the measurement at 2000 µm and 1500 µm from the fovea in temple, CT in amblyopic eyes were significantly thicken than the fellow eyes (p < 0.05). Compared with the fellow eyes, the CT of certain areas were thicker in the amblyopic eyes. Though the FAZ size of the amblyopic eyes was larger in SCPL/DCPL layers, the retinal vascular density indices in SCPL/DCPL were lower in amblyopia eyes without statistical difference. Angio-OCT may be an effective way to evaluate the status of the choroidal and retinal vascular system in amblyopic children.

Dynamic Changes in Retinal Vessel Diameters and Arteriovenous Ratio within 10 Days of Birth

Purpose This study monitored the dynamic changes in retinal vascular width and the AVR in full-term neonates within 1–10 days of birth. Methods It was conducted at hospitals in the Anhui province from October 2020 to March 2022. A total of 700 full-term, healthy infants were chosen randomly within 10 days of birth, and the Star Pupil Medical Cloud Data System (XBDS) was used to collect fundus images. Infants within 6 days of birth were grouped into groups one to six, while those within the 7th to 10th days were grouped into group seven. The fundus photographs were imported into Image-Pro-Plus (IPP) software. The optic disc diameter was measured. The retinal artery and vein’s diameter was measured at a distance between 0.5- and 1.0-disc diameter from the optic disc’s margin. The AVR was also calculated. Finally, each group’s retinal vessel diameters and AVR were compared separately to show their dynamic changes. Results There were differences in the retinal artery diameter between groups one and two, three and four, four and five, and five and six. For retinal vein diameter, there were differences between groups one and two and groups six and seven. There were also differences in the AVR between all groups. In addition, there was a significant positive correlation between the small retinal artery and vein diameters. Conclusion The retinal artery and vein diameters and AVR in neonates change dynamically during the first 10 days of life. The AVR undergoes the most dramatic change daily and is considerably smaller than the AVR in adults. Hence, this study found that the external environment undergoes significant changes following birth that affect the microcirculation. Then, the retinal central vascular system undergoes similar emergency and adaptive alterations.

Changes of Optic Disc and Macular Vessel Perfusion Density in Primary Angle Closure Glaucoma: A Quantitative Study Using Optical Coherence Tomography Angiograph

Introduction: This study aims to investigate the changes of retinal vascular system in primary angle closure glaucoma (PACG) and acute primary angle closure (APAC) by optical coherence tomography (OCT) angiograph (OCTA) and to evaluate the diagnostic ability of changes of vessel density (VD) in different sectors and layers of optic disc and macular area in APAC and PACG. Methods: In this cross-sectional, observational study, 21 APAC patients (22 eyes) and 21 PACG patients (27 eyes) along with 17 healthy people were enrolled from August 2018 to March 2019. Optic disc region and macular region were imaged using swept-source OCTA system. VD of the macular region was quantified by Image J (1.52a, USA) and Matlab 2018a. The circumpapillary retinal nerve fiber layer (cpRNFL) thickness and ganglion cell complex thickness were obtained by spectral-domain OCT. Results: Compared with the healthy group, the cpRNFL thickness in superior sector was thicker in the APAC group, and this area had the most diffuse microvascular dropout as well. The difference in the macular superficial capillary plexus (SCP) VD between APAC and the control group was not statistically significant. The area under the ROC curves (AUC) of the total optic disc VD in the radial peripapillary capillary (RPC) layer was higher than the AUC of the papillary VD in the optic nerve head (ONH) layer. Compared to the control group, the total optic disc VD, peripapillary VD, and each quadrant of peripapillary VD were decreased in PACG (p < 0.01). In PACG macular region, SCP VD, and deep capillary plexus (DCP) VD, parafovea VD (except temporal sectors) decreased (p < 0.01). The PACG eyes had a greater decrease percentage of VD in total ONH than total macula. The diagnostic value of the VD in the ONH layer and the RPC layer was similar. The diagnostic value of the SCP VD in the macula was greater than the DCP VD in the macula. The AUC was no significant difference between cpRNFL thickness and the total optic disc VD AUC. Conclusion: Elevated intraocular pressure preferentially affects vascular perfusion in the optic disc region more than the macular region in APAC and PACG. In the APAC eyes, there was a perfusion defect in the optic disc region and an increase in RNFL thickness. In this study, the OCTA vascular parameters have similar performance to the OCT structural parameters for glaucoma diagnosis in PACG.

Peripheral white blood cell subtypes and the development/progression of diabetic macular edema in type 2 diabetic patients: a comparative study.

Inflammation and immune dysregulation are involved in the pathogenesis of diabetic macular edema (DME). The progressive increase of neutrophils in peripheral blood can lead to the increase of the number of neutrophils in the retina, thus leading to the sustained damage of the retinal vascular system and the destruction of the blood retinal barrier (BRB); lymphocytes play a protective role in vascular diseases caused by type 2 diabetes mellitus (T2DM). The purpose of this study was to study the relationship between the changes of leukocytes and their classification in peripheral blood and the occurrence and progression of DME in patients with T2DM. A retrospective analysis was made on 81 patients with T2DM with DME (DME group) hospitalized in our hospital from January 2019 to December 2020. According to the morphological characteristics of macular edema in optical coherence tomography (OCT), they were divided into early DME group (n=33) and late DME group (n=48); 33 patients with diabetes retinopathy (DR) but without DME matched in age and course of disease served as the control group (NO-DME group). The clinical parameters assessed included eye examination, OCT results, WBCs and subtypes, blood glucose, and glycosylated hemoglobin. Compared with NO-DME group (n=33), Neutrophils% in DME group (n=81) was higher (57.37±9.52 vs. 63.27±7.85; P=0.001); Monocyte% (7.63±1.77 vs. 6.88±1.83; P=0.047) and lymphocyte% (30.35±9.51 vs. 27.26±6.59; P=0.032) were decreased. The optimal model was obtained with R 4.0.5 software. With other relevant variables being the same, females had a significantly increased risk of DME (b=1.273, P=0.015), %neutrophils was significantly associated with increased risk of DME (b=0.152, P=0.0006), and %lymphocytes was significantly associated with a reduced risk of DME (b=-0.027, P=0.179). However, in the early and late DME groups, no significant differences in biological markers were found, and a high-quality model was not obtained. In this preliminary study, %neutrophils is associated with increased risk of DME, whereas %lymphocytes is associated with a reduced risk of DME.

Optimization of diagnostics of retinopathy of prematurity stages based on the integration of clinical data using the Key to Diagnosis I software

Despite the improvement of algorithms of preterm infants’ management, methods for predicting, diagnosing and treating ROP remains a vital issue. Purpose: to improve the diagnostics of retinopathy of prematurity based on the assessment of vascular system configuration, using Key to Diagnosis I software. Material and methods. 279 patients with ROP were divided into 6 groups: group 1 included 152 patients (304 eyes) with stage I; group 2 — 45patients (90 eyes) with stage II; group 3 — 8patients (12 eyes) with stage III; group 4 — 7 patients (8 eyes) with stage IVA; group 5 — 7 patients (14 eyes) with posterior aggressive ROP; control group 6 — 60patients (120 eyes) diagnosed with immature retina who have no ROP signs. 28 eyes were analyzed using wide-field imaging, while 400 eyes were analyzed by separate images. The presence o f“mute” zones, macula localization, traction index of the macular zone (Tm), zone and span of pathological changes, fractal dimension (Df) and complexity of vascular system (СVS) were assessed on automatically created wide-field images, obtained by Ret-Cam Shuttle. Results. We revealed strong correlation between Df and stages (p = 0.85, p = 0.01); moderate negative correlation of Тm and stages (p = 0.62, p = 0.01), except for posterior aggressive ROP; strong positive correlation between CVS and stages ( p = 0.91, p = 0.001). Diagnostic modules of the software have been developed to create wide-field fundus imaging in infants, localize the macula as a marker for morphometry, and isolate the vascular system using deep convolutional neural networks. Conclusions. The developed algorithm for multivari­ate analysis of the retinal vascular system reduces the risks of subjective assessment of retinal changes.

Pathogenesis of diabetic macular edema: the role of pro-inflammatory and vascular factors. Aliterature review

The review presents data on the pathogenesis of diabetic macular edema (DME). DME is a major cause of visual impairment in type 2 diabetes mellitus (DM) patients. Non-specific inflammation is an important factor of the underlying processes of DME. The importance of vascular endothelial growth factor (VEGF), interleukin-6, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1, vascular cell adhesion molecule-1 in the development of diabetes microvascular complications is indicated. Intercellular adhesion molecules (ICAM), particularly, soluble ICAM-1 (sICAM-1), are a local inflammatory mediator involved in the pathogenesis of diabetic injury to the layers of the eye. The literature is scant on the assessment of sICAM-1 in type2 DM patients with diabetic injury to the neurovascular system of the eye (i.e. adhesion of leukocytes to the vascular endothelium (leukostasis) and the concurrent endothelial apoptosis). There are three main stages of microvascular changes due to nonspecific inflammation: dilation of capillaries and increased blood flow, microvascular structural changes and leakage of plasma proteins from the bloodstream, transmigration of leukocytes through the endothelium and accumulation at the site of injury. Vascular dysfunction in diabetic retinopathy (DR) and DMЕ is caused primarily by leukostasis, which is based on the recruitment and adhesion of leukocytes to the retinal vascular system. Leukostasis is the first step in the sequence of adhesion and activation events that lead to the infiltration of leukocytes through the endothelium. Leukocytes involved in leukostasis induce vascular permeability by releasing cytokines, including VEGF and TNF-α, contributing to endothelial protein binding, increasing levels of reactive oxidative substances, and killing pericytes and astrocytes surrounding the endothelium. Thus, the existing data on the main aspects of the pathogenesis of DMЕ indicate that inflammation is an important factor in the processes underlying the development of DMЕ and DR. But a new understanding of the physiology of the retina suggests that the pathogenesis of retinal lesions in type 2 DM can be considered as a change in the neurovascular unit of the retina.

Automated Diagnosis of Optical Coherence Tomography Angiography (OCTA) Based on Machine Learning Techniques.

Diabetic retinopathy (DR) refers to the ophthalmological complications of diabetes mellitus. It is primarily a disease of the retinal vasculature that can lead to vision loss. Optical coherence tomography angiography (OCTA) demonstrates the ability to detect the changes in the retinal vascular system, which can help in the early detection of DR. In this paper, we describe a novel framework that can detect DR from OCTA based on capturing the appearance and morphological markers of the retinal vascular system. This new framework consists of the following main steps: (1) extracting retinal vascular system from OCTA images based on using joint Markov-Gibbs Random Field (MGRF) model to model the appearance of OCTA images and (2) estimating the distance map inside the extracted vascular system to be used as imaging markers that describe the morphology of the retinal vascular (RV) system. The OCTA images, extracted vascular system, and the RV-estimated distance map is then composed into a three-dimensional matrix to be used as an input to a convolutional neural network (CNN). The main motivation for using this data representation is that it combines the low-level data as well as high-level processed data to allow the CNN to capture significant features to increase its ability to distinguish DR from the normal retina. This has been applied on multi-scale levels to include the original full dimension images as well as sub-images extracted from the original OCTA images. The proposed approach was tested on in-vivo data using about 91 patients, which were qualitatively graded by retinal experts. In addition, it was quantitatively validated using datasets based on three metrics: sensitivity, specificity, and overall accuracy. Results showed the capability of the proposed approach, outperforming the current deep learning as well as features-based detecting DR approaches.

Diminution in the Expression of Markers of Diabetic Retinopathy in Human Retinal Microvascular Endothelial Cells by Arctiin

Microvascular complications of diabetes-associated inflammation lead to diabetic retinopathy. However, the molecular mechanism and the biochemical process underlying this process are not well understood. The present study is an attempt to investigate the role of a Chinese herbal compound, arctiin, on the human retinal microvascular endothelial cells damage, a cellular model for diabetic retinopathy, caused by proinflammatory cytokines such as interleukin-10 and interleukin-1β. The results of the study show that arctiin possessed a strong inhibitory potential against interleukin-10 and interleukin-1β with IC50 values less than 0.86 μM and 0.93 μM, respectively. These data also correlate with the results from the computational analysis with a total docking score of -322.524 kJ/mol and -395.026 kJ/mol for interleukin-10 and interleukin-1β, respectively. The results herein also show that the administration of interleukin-10 and interleukin-1β accelerated the leakage of the retinal vascular system and apoptosis of the endothelial cell. In conclusion, the interleukin-10 and interleukin-1β signaling pathway may serve as a potential target for preventing diabetic retinopathy.

Prediction Algorithm of Young Students' Physical Health Risk Factors Based on Deep Learning.

Young people's physical and mental health is the foundation of society's overall development and the key to improving people's health quality. Middle school students' physical examinations and monitoring work are a surefire way to ensure their healthy development. Poor vision, dental caries, overweight and obesity, and high blood pressure are the most common adverse health outcomes of students caused by adolescent health risk behavior factors. Researchers have been concerned about the retinal fundus vascular system, which is the only internal vascular system that can be observed in a noninvasive state of the human body. Fundus images contain a wealth of disease-related information. Fundus images have been widely used in the field of medical auxiliary diagnosis because many important systemic diseases of the human body cause specific reactions in the fundus. Aiming to solve the problem of inseparable tiny blood vessels, this paper proposes a model of retinal vessel segmentation based on attention mechanisms. In light of the retinal arteriovenous division of discontinuous challenges, the topological structure of the constraint system along with overcoming the network and topology restrictions is monitored. Finally, simulation experiments were conducted on two publicly available datasets. The findings show that the proposed method is reliable, effective, and accurate in predicting physical health risk factors in adolescent students.