Retinal Microvascular Damage Research Articles

Artificial Intelligence-Assisted Perfusion Density as Biomarker for Screening Diabetic Nephropathy.

To identify a reliable biomarker for screening diabetic nephropathy (DN) using artificial intelligence (AI)-assisted ultra-widefield swept-source optical coherence tomography angiography (UWF SS-OCTA). This study analyzed data from 169 patients (287 eyes) with type 2 diabetes mellitus (T2DM), resulting in 15,211 individual data points. These data points included basic demographic information, clinical data, and retinal and choroidal data obtained through UWF SS-OCTA for each eye. Statistical analysis, 10-fold cross-validation, and the random forest approach were employed for data processing. The degree of retinal microvascular damage in the diabetic retinopathy (DR) with the DN group was significantly greater than in the DR without DN group, as measured by SS-OCTA parameters. There were strong associations between perfusion density (PD) and DN diagnosis in both the T2DM population (r = -0.562 to -0.481, P < 0.001) and the DR population (r = -0.397 to -0.357, P < 0.001). The random forest model showed an average classification accuracy of 85.8442% for identifying DN patients based on perfusion density in the T2DM population and 82.5739% in the DR population. Quantitative analysis of microvasculature reveals a correlation between DR and DN. UWF PD may serve as a significant and noninvasive biomarker for evaluating DN in patients through deep learning. AI-assisted SS-OCTA could be a rapid and reliable tool for screening DN. We aim to study the pathological processes of DR and DN and determine the correspondence between their clinical and pathological manifestations to further clarify the potential of screening DN using AI-assisted UWF PD.

Indoxyl sulfate induces retinal microvascular injury via COX-2/PGE2 activation in diabetic retinopathy

BackgroundDiabetic retinopathy (DR), the principal cause of acquired blindness among the working-age population, is the most frequent microvascular complication of diabetes. Although metabolic disorders are hypothesized to play a role in its pathogenesis, the underlying mechanism remains largely elusive.MethodsTo elucidate the mechanism, we initially compared metabolite profiles of vitreous fluid between 23 patients with DR and 12 non-diabetic controls using liquid chromatography/tandem mass spectrometry, identifying the distinct metabolite indoxyl sulfate (IS). Subsequently, streptozotocin (STZ)-induced diabetic and IS-injected rat models were established to examine the effects of IS on retinal microvasculature. RNA sequencing was conducted to identify potential regulatory mechanisms in IS-treated human retinal endothelial cells (HREC). Finally, target gene knockdown in HREC and treatment of IS-injected rats with inhibitors (targeting IS production or downstream regulators) were employed to elucidate the detailed mechanisms and identify therapeutic targets for DR.ResultsMetabolomics identified 172 significantly altered metabolites in the vitreous humor of diabetics, including the dysregulated tryptophan metabolite indoxyl sulfate (IS). IS was observed to breach the blood-retinal barrier and accumulate in the intraocular fluid of diabetic rats. Both in vivo and in vitro experiments indicated that elevated levels of IS induced endothelial apoptosis and disrupted cell junctions. RNA sequencing pinpointed prostaglandin E2 (PGE2) synthetase-cyclooxygenase 2 (COX-2) as a potential target of IS. Validation experiments demonstrated that IS enhanced COX-2 expression, which subsequently increased PGE2 secretion by promoting transcription factor EGR1 binding to COX-2 DNA following entry into cells via organic anion transporting polypeptides (OATP2B1). Furthermore, inhibition of COX-2 in vivo or silencing EGR1/OATP2B1 in HREC mitigated IS-induced microcapillary damage and the activation of COX-2/PGE2.ConclusionOur study demonstrated that indoxyl sulfate (IS), a uremic toxin originating from the gut microbiota product indole, increased significantly and contributed to retinal microvascular damage in diabetic retinopathy (DR). Mechanistically, IS impaired retinal microvascular integrity by inducing the expression of COX-2 and the production of PGE2. Consequently, targeting the gut microbiota or the PGE2 pathway may offer effective therapeutic strategies for the treatment of DR.Graphical

Allicin Mitigates Diabetic Retinopathy in Rats by Activating Phosphatase and Tensin Homolog-induced Kinase 1/Parkin-mitophagy and Inhibiting Oxidative Stress-mediated NOD-like Receptor Family Pyrin Domain Containing 3 Inflammasome.

Diabetic retinopathy (DR) is one of the significant disabling outcomes of diabetes mellitus characterized by retinal microvascular damage, inflammation, and neuronal dysfunction. Allicin (Alc), a natural compound found in garlic, has garnered attention for its antioxidant and anti-inflammatory properties, positioning it as a potential therapeutic agent for DR. The aim of the present study was to investigate the therapeutic efficacy of Alc in DR management and elucidate its underlying mechanisms of action. We established a DR model in male Sprague-Dawley rats (n = 50, 200-250 g, 12 weeks old) using a high-fat diet for 8 weeks plus a low dose of streptozotocin administered at the start of the 4th week. The diabetic (Diab) animals were administered Alc (16 mg/kg/day, orally), either alone or in combination with mitochondrial division inhibitor-1 (Mdivi-1) as a mitophagy inhibitor, starting 28 days before tissue sampling. We evaluated histopathological changes, metabolic abnormalities associated with type 2 diabetes mellitus (T2DM), the expression of proteins regulating pyroptosis (NOD-like receptor family pyrin domain containing 3, cleaved-caspase 1, and gasdermin D-N terminal) and mitophagy (phosphatase and tensin homolog-induced kinase 1 [PINK1] and Parkin), as well as the levels of oxidative stress mediators and proinflammatory cytokines. Alc treatment effectively ameliorated histopathological changes and metabolic abnormalities associated with T2DM. It downregulated pyroptosis-related proteins, upregulated mitophagy-related proteins, reduced proinflammatory cytokine levels, and attenuated oxidative stress. Treatment with Mdivi-1 suppressed the beneficial effects of Alc. Our findings highlight the therapeutic potential of Alc in managing DR by targeting multiple pathophysiological pathways, including pyroptosis, inflammation, and oxidative stress. The observed antipyroptotic effects of Alc were partially mediated by the activation of the PINK1/parkin-mediated mitophagy pathway. Additional studies are necessary to thoroughly understand the therapeutic mechanisms of Alc and its viability as a treatment choice for DR.

Plasma Metabolomics Identifies Key Metabolites and Improves Prediction of Diabetic Retinopathy: Development and Validation across Multinational Cohorts

PurposeTo identify longitudinal metabolomic fingerprints of diabetic retinopathy (DR) and evaluate their utility in predicting DR development and progression. DesignMulticenter, multi-ethnic cohort study. ParticipantsThis study included 17,675 participants with baseline pre-diabetes/diabetes, in accordance with the 2021 American Diabetes Association guideline, and free of baseline DR from the UK Biobank (UKB); and an additional 638 diabetic participants from the Guangzhou Diabetic Eye Study (GDES) for external validation. MethodsLongitudinal DR metabolomic fingerprints were identified through nuclear magnetic resonance assay in UKB participants. The predictive value of these fingerprints for predicting DR development were assessed in a fully withheld test set. External validation and extrapolation analyses of DR progression and microvascular damage were conducted in the GDES cohort. Model assessments included the C-statistic, net classification improvement (NRI), integrated discrimination improvement (IDI), calibration, and clinical utility in both cohorts. Main Outcome MeasuresDR development, progression, and retinal microvascular damage. ResultsOf 168 metabolites, 118 were identified as candidate metabolomic fingerprints for future DR development. These fingerprints significantly improved the predictability for DR development beyond traditional indicators (C-statistic: 0.802, 95% CI, 0.760–0.843 vs. 0.751, 95% CI, 0.706–0.796; P = 5.56×10−4). Glucose, lactate, and citrate were among the fingerprints validated in the GDES cohort. Using these parsimonious and replicable fingerprints yielded similar improvements for predicting DR development (C-statistic: 0.807, 95% CI, 0.711–0.903 vs. 0.617, 95% CI, 0.494, 0.740; P = 1.68×10−4) and progression (C-statistic: 0.797, 95% CI, 0.712–0.882 vs. 0.665, 95% CI, 0.545–0.784; P = 0.003) in the external cohort. Improvements in NRIs, IDIs, and clinical utility were also evident in both cohorts (all P <0.05). In addition, lactate and citrate were associated to microvascular damage across macular and optic disc regions (all P <0.05). ConclusionsMetabolomic profiling has proven effective in identifying robust fingerprints for predicting future DR development and progression, providing novel insights into the early and advanced stages of DR pathophysiology.

Retinal Perfusion Analysis of Children with Diabetes Mellitus Type 1 Using Optical Coherence Tomography Angiography.

(1) Background: This study aims to evaluate retinal perfusion by optical coherence tomography angiography (OCTA) in pediatric patients with type 1 diabetes mellitus (T1D) without diabetic retinopathy (DR). (2) Methods: Thirty-one patients affected by T1D were enrolled. All participants were evaluated using OCTA. The foveal avascular zone (FAZ) and superficial and deep macular vessel density (VD) were analyzed. The correlation of these parameters with metabolic factors such as body mass index (BMI), glycated hemoglobin (HbA1c), and the type of insulin therapy (multiple daily injections, MDI vs. continuous subcutaneous insulin infusion, CSII) was determined. (3) Results: None of the OCTA parameters were significantly different between the groups. The patients' HbA1C level did not influence any of the OCTA parameters. The use of MDI tended to reduce the parafoveal and perifoveal deep VD (p = 0.048 and p = 0.021, respectively) compared to CSII. An elevated BMI tended to increase the deep macular (p = 0.005) and perifoveal VD (p = 0.006). (4) Conclusion: VD and FAZ are normal in pubescent children with T1D without signs of DR. Treatment with CSII may be a better choice compared to MDI, as CSII may be protective against retinal microvascular damage. Our results indicate the need for new clinical parameters of glycemic control in addition to HbA1c which could assess the risk of DR.

Retinal Vascular Abnormalities and Clinical Parameters in Systemic Sclerosis.

Background: Systemic sclerosis is a complex autoimmune disease characterized by vasculopathy, fibrosis, and immune dysregulation. Ocular manifestations in these patients are increasingly recognized, suggesting potential correlations between systemic vascular abnormalities and ocular microvascular changes. Advancements in molecular immunology and imaging technology using ocular coherence tomography (OCT) have unveiled intricate pathways underlying possible disease pathogenesis. Understanding the interplay between retinal vascular abnormalities and molecular immunology parameters could provide insights into disease mechanisms and potential biomarkers. Purpose: The aim of this study was to investigate vascular abnormalities, detected with optical coherence tomography angiography (OCT-A), in systemic sclerosis patients and to find correlations between the severity of the disease detected with molecular immunology findings and OCT-A parameters. Methods: A group of 32 systemic sclerosis patients were compared with 9 healthy controls. Ganglion cell complex thickness (GCC), retina thickness of the fovea and parafovea, nerve fiber layer thickness (RNFL) and cup/disc area ratio were investigated using OCT. Vessel density (VD) of the superficial (SCP) and deep capillary plexus (DCP) of the whole macular area and ETDRS grid, size of the foveal avascular zone (FAZ) and vessel density of the radial peripapillary capillary plexus (RPCP) were evaluated using OCT-A. Modified Rodnan skin score (mRSS), capillaroscopy and disease duration were used to stage disease severity. Results: There was a statistically significant reduction in retina thickness of the fovea and parafovea, VD of the whole DCP, VD of the SCP and DCP in ETDRS grid in the patient group compared to controls (p < 0.001). The patients presented a significant enlargement of the FAZ (p 0.005). No significant correlation between OCT and OCT-A parameters and disease severity scores was found. Conclusions: OCT-A could represent a non-invasive tool to detect retinal microvascular damage in systemic sclerosis.

Syringaresinol Alleviates Early Diabetic Retinopathy by Downregulating HIF-1α/VEGF via Activating Nrf2 Antioxidant Pathway.

Early diabetic retinopathy (DR) is characterized by chronic inflammation, excessive oxidative stress, and retinal microvascular damage. Syringaresinol (SYR), as a natural polyphenolic compound, has been proved to inhibit many disease progression due to its antiinflammatory and antioxidant properties. The present study focuses on exploring the effect of SYR on hyperglycemia-induced early DR as well as the underlying mechanisms. Wild-type (WT) and nuclear factor erythroid 2-related factor 2 (Nrf2)-knockout C57BL/6 mice of type 1 diabetes and high glucose (HG)-induced RF/6A cells are used as in vivo and in vitro models, respectively. This study finds that SYR protects the retinal structure and function in diabetic mice and reduces the permeability and apoptosis of HG-treated RF/6A cells. Meanwhile, SYR distinctly mitigates inflammation and oxidative stress in vivo and vitro. The retinal microvascular damages are suppressed by SYR via downregulating hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway. Whereas, SYR-provided protective effects are diminished in Nrf2-knockout mice, indicating that SYR improves DR progression by activating Nrf2. Similarly, SYR cannot exert protective effects against HG-induced oxidative stress and endothelial injury in small interfering RNA (siRNA)-Nrf2-transfected RF/6A cells. In summary, SYR suppresses oxidative stress via activating Nrf2 antioxidant pathway, which ameliorates retinal microvascular damage by downregulating HIF-1α/VEGF, thereby alleviating early DR progression.

Unveiling a Novel Trend: Belimumab Amplifies Retinal Microvascular Density Decline in Lupus Nephritis Patients Revealed by Optical Coherence Tomography Angiography

Background: In systemic lupus erythematosus (SLE), retinopathy is connected to severe disease and poorer prognosis. This study aimed to investigate changes in retinal vascular density (VD) in SLE and lupus nephritis (LN) patients and to examine the effects of Belimumab and hydroxychloroquine (HCQ) on retinal VD in these patients. Methods: This cross-sectional study enrolled 54 SLE patients (21 with LN and 33 without LN). A comprehensive ophthalmological evaluation using optical coherence tomography angiography (OCTA) was conducted on SLE patients. Rheumatological evaluations were performed through the collection of relevant clinical and laboratory data, as well as the assessment of rheumatological treatment. Results: We found that the mean VD in the superficial capillary plexus (SCP-VD) of most regions showed a significant decrease in the LN group. Further analysis revealed that LN patients using Belimumab exhibited a reduction in SCP-VD and deep capillary plexus VD (DCP-VD) (P&lt;0.05). Furthermore, LN patients who had been using HCQ for more than 5 years exhibited a notable decrease in DCP-VD. Notably, SCP-VD and the cumulative dose of HCQ demonstrated a significant negative correlation. Conclusion: This study provides insights into the changes in retinal vascular density in LN patients and highlights the potential impact of long-term Belimumab and HCQ treatment on retinal microvascular damage. These findings contribute to the development of effective strategies for preventing and managing retinal complications in LN patients.

Multi-parametric Retinal Microvascular Functional Perfusion Imaging Based on Dynamic Fundus Fluorescence Angiography.

Retinal microvascular disease has caused serious visual impairment widely in the world, which can be hopefully prevented via early and precision microvascular hemodynamic diagnosis. Due to artifacts from choroidal microvessels and tiny movements, current fundus microvascular imaging techniques including fundus fluorescein angiography (FFA) precisely identify retinal microvascular microstructural damage and abnormal hemodynamic changes difficulty, especially in the early stage. Therefore, this study proposes an FFA-based multi-parametric retinal microvascular functional perfusion imaging (RM-FPI) scheme to assess the microstructural damage and quantify its hemodynamic distribution precisely. Herein, a spatiotemporal filter based on singular value decomposition combined with a lognormal fitting model was used to remove the above artifacts. Dynamic FFAs of patients (n = 7) were collected first. The retinal time fluorescence intensity curves were extracted and the corresponding perfusion parameters were estimated after decomposition filtering and model fitting. Compared with in vivo results without filtering and fitting, the signal-to-clutter ratio of retinal perfusion curves, average contrast, and resolution of RM-FPI were up to 7.32 ± 0.43 dB, 14.34 ± 0.24 dB, and 11.0 ± 2.0 μm, respectively. RM-FPI imaged retinal microvascular distribution and quantified its spatial hemodynamic changes, which further characterized the parabolic distribution of local blood flow within diameters ranging from 9 to 400 μm. Finally, RM-FPI was used to quantify, visualize, and diagnose the retinal hemodynamics of retinal vein occlusion from mild to severe. Therefore, this study provided a scheme for early and precision diagnosis of retinal microvascular disease, which might be beneficial in preventing its development.

On implications of somatostatin in diabetic retinopathy.

Somatostatin, a naturally produced neuroprotective peptide, depresses excitatory neurotransmission and exerts anti-proliferative and anti-inflammatory effects on the retina. In this review, we summarize the progress of somatostatin treatment of diabetic retinopathy through analysis of relevant studies published from February 2019 to February 2023 extracted from the PubMed and Google Scholar databases. Insufficient neuroprotection, which occurs as a consequence of declined expression or dysregulation of retinal somatostatin in the very early stages of diabetic retinopathy, triggers retinal neurovascular unit impairment and microvascular damage. Somatostatin replacement is a promising treatment for retinal neurodegeneration in diabetic retinopathy. Numerous pre-clinical and clinical trials of somatostatin analog treatment for early diabetic retinopathy have been initiated. In one such trial (EUROCONDOR), topical administration of somatostatin was found to exert neuroprotective effects in patients with pre-existing retinal neurodysfunction, but had no impact on the onset of diabetic retinopathy. Overall, we concluded that somatostatin restoration may be especially beneficial for the growing population of patients with early-stage retinopathy. In order to achieve early prevention of diabetic retinopathy initiation, and thereby salvage visual function before the appearance of moderate non-proliferative diabetic retinopathy, several issues need to be addressed. These include the needs to: a) update and standardize the retinal screening scheme to incorporate the detection of early neurodegeneration, b) identify patient subgroups who would benefit from somatostatin analog supplementation, c) elucidate the interactions of somatostatin, particularly exogenously-delivered somatostatin analogs, with other retinal peptides in the context of hyperglycemia, and d) design safe, feasible, low cost, and effective administration routes.

Topical Nerve Growth Factor (NGF) restores electrophysiological alterations in the Ins2Akita mouse model of diabetic retinopathy

People suffering from diabetes mellitus commonly have to face diabetic retinopathy (DR), an eye disease characterized by early retinal neurodegeneration and microvascular damage, progressively leading to sight loss. The Ins2Akita (Akita) diabetic mouse presents the characteristics of DR and experimental drugs can be tested on this model to check their efficacy before going to the clinic. Topical administration of Nerve Growth Factor (NGF) has been recently demonstrated to prevent DR in the Akita mouse, reverting the thinning of retinal layers and protecting the retinal ganglion cells (RGCs) from death. In this study, we characterize the effects of topical NGF on neuroretina function, quantified with the electroretinogram (ERG). In particular, we show that NGF can ameliorate RGC conduction in the retina of Akita mice, which correlates with a recovery of retinal nerve fiber plus ganglion cell layer (RNFL-GCL) structure. Overall, our preclinical results highlight that topical administration of NGF could be a promising therapeutic approach for DR, being capable of exerting a beneficial impact on retinal functionality.

Brain and Cognition Signature Fingerprinting Vascular Health in Diabetic Individuals: An International Multi-Cohort Study

To evaluate the correlation between cognitive signatures and the risk of diabetic vascular complications and mortality, based on a multicountry prospective study. The participants comprised 27,773 diabetics from the UK Biobank (UKB) and 1307 diabetics from the Guangzhou Diabetic Eye Study (GDES) cohort. The exposures were brain volume and cognitive screening tests for UKB participants, whilst the global cognitive score (GCS) measuring orientation to time and attention, episodic memory, and visuospatial abilities were determined for GDES participants. The outcomes for the UKB group were mortality, as well as macrovascular (myocardial infarction [MI] and stroke), microvascular (end-stage renal disease [ESRD], and diabetic retinopathy [DR]) events. The outcomes for the GDES group were retinal and renal microvascular damage. In the UKB group, a 1-SD reduction in brain gray matter volume was associated with 34%-77% higher risks of incident MI, ESRD, and DR. The presence of impaired memory was associated with 18%-73% higher risk of mortality and ESRD; impaired reaction was associated with 1.2-1.7-fold higher risks of mortality, stroke, ESRD, and DR. In the GDES group, the lowest GCS tertile exhibited 1.4-2.2-fold higher risk of developing referable DR and a twofold faster decline in renal function and retinal capillary density compared with the highest tertile. Restricting data analysis to individuals aged less than 65 years produced consistent results. Cognitive decline significantly elevates the risk of diabetic vascular complications and is correlated with retinal and renal microcirculation damage. Cognitive screening tests are strongly recommended as routine tools for management of diabetes.

Clinical Observation of Macular Superficial Capillary Plexus and Ganglion Cell Complex in Patients with Parkinson’s Disease

Introduction: We investigated macular superficial capillary plexus (SCP) density and the thicknesses of the ganglion cell complex (GCC) in patients with Parkinson’s disease (PD) and correlated them. We also observed the correlations between SCP density and clinical parameters of PD patients. The retina might be a novel biomarker of PD and will be useful in the future for the early diagnosis of PD and detecting disease progression. Methods: Seventy-four participants (38 patients with PD and 36 healthy controls) were recruited at the Affiliated Hospital of Xuzhou Medical University between January 2022 and June 2022 in this study. The macular SCP densities was measured by optical coherence tomography angiography (OCTA), and the GCC thickness was measured by optical coherence tomography (OCT). The parameters were compared between PD patients and healthy controls. The correlation between SCP and clinical parameters was tested. Results: Compared with the control group, PD patients showed reduced SCP densities in all areas of the macular region (parafovea-temporal: t = 3.053, p = 0.003; parafovea-superior: t = 3.680, p = 0.001; parafovea-nasal: t = 4.643, p < 0.001; parafovea-inferior: t = 2.254, p = 0.027; perifovea-temporal: t = 3.798, p < 0.001; perifovea-superior: t = 3.014, p = 0.004; perifovea-nasal: t = 2.948, p = 0.004; perifovea-inferior: t = 3.337, p = 0.021). The average GCC thickness in the PD patients was significantly reduced (t = 2.365, p = 0.021). There were positive correlations between the average GCC thickness and the SCP densities in most of the areas of the macular regions in PD patients (parafovea-temporal: r = 0.325, p = 0.005; parafovea-superior: r = 0.295, p = 0.011; parafovea-nasal: r = 0.335, p = 0.003; perifovea-superior: r = 0.362, p = 0.002; perifovea-nasal: r = 0.290, p = 0.012; perifovea-inferior: r = 0.333, p = 0.004). We found significant correlations between SCP densities and Hoehn and Yahr (H and Y) scales, UPDRS III scores, and MMSE scores. No significant correlation was observed between SCP density and PD disease duration (all p > 0.05). Conclusions: We demonstrated that the macular SCP density was decreased, and the average GCC thickness was reduced in PD patients. The correlation between SCP density damage and GCC thinning also suggested that the retinal microvascular damage may be associated with retinal structural degeneration in PD patients. OCTA and OCT may be considered objective biomarkers for detecting microvascular impairment and neuronal damage in the early stages of PD in the future.

Silymarin reduces retinal microvascular damage in streptozotocin-induced diabetic rats

Diabetic retinopathy is a severe microvascular problem in diabetes mellitus. Silymarin is a flavonoid compound, and according to previous studies, it is a bioactive compound with potent antioxidant and anti-inflammatory properties. This investigation aims to peruse the impact of silymarin against diabetic retinopathy in streptozotocin (STZ)-provoked rats. Thirty-two adult male Wistar rats were randomly allocated into the control group, STZ group, STZ + silymarin (50 mg/kg), and STZ + silymarin (100 mg/kg). STZ rats received silymarin every day until 2 months after diabetes induction. The serum and retinal tissues were collected 2 months after silymarin treatment to determine biochemical and molecular analyses. Silymarin markedly lowered the serum glucose concentration in diabetic rats. Silymarin reduced the increased levels of advanced glycosylated end products (AGEs), the receptors for AGEs (RAGE), and reactive oxygen species (ROS) in diabetic rats. Silymarin also attenuated the phosphorylation of p38 MAP kinase and nuclear factor (NF)-κB p65 and diminished diabetes-induced overexpression of inflammatory cytokines, vascular endothelial growth factor (VEGF), adhesion molecules, and extracellular matrix proteins in STZ rats. Our data suggested that silymarin has protective effects against diabetic retinopathy, which might be related to the inhibition of the AGEs/RAGE axis and its antioxidant and anti-inflammatory activities.

P35 Dermatomyositis with retinal involvement: a case series

P35 Dermatomyositis with retinal involvement: a case series

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.

A novel interaction between soluble epoxide hydrolase and the AT1 receptor in retinal microvascular damage

Clinical studies have suggested that the renin-angiotensin system (RAS) may be a promising therapeutic target in treating diabetic retinopathy (DR). While AT1 receptor blockade decreased the incidence of DR in the DIRECT trial, it did not reduce the DR progression. Lack of understanding of the molecular mechanism of retinal microvascular damage induced by RAS is a critical barrier to the use of RAS blockade in preventing or treating DR. The purpose of this study is to investigate the interaction between soluble epoxide hydrolase (sEH) and the AT1 receptor in Angiotensin II (Ang II)- and diabetes-induced retinal microvascular damage. We demonstrate that Ang II increases retinal sEH levels, which is blunted by an AT1 blocker; administration of 11,12-epoxyeicosatrienoic acid (EET) exacerbates intravitreal Ang II-induced retinal albumin leakage; while sEH knockout (KO) and blockade reduce Ang II-induced retinal vascular remodeling, sEH KO causes retinal vascular leakage in Ang II-sEH KO mice; and sEH KO potentiates diabetes-induced retinal damage via promoting retinal vascular endothelial growth factor (VEGF) but reducing expression of tight junction proteins (ZO-1 and occludin). Our studies hold the promise of providing a new strategy, the use of combined EETs blockade with AT1 blocker, to prevent or reduce DR.

A Network Pharmacology to Explore the Mechanism of Astragalus Membranaceus in the Treatment of Diabetic Retinopathy.

Background Diabetic retinopathy (DR) includes a series of typical lesions affected by retinal microvascular damage caused by diabetes mellitus (DM), which not only seriously damages the vision, affecting the life's quality of patients, but also brings a considerable burden to the family and society. Astragalus Membranaceus (AM) is a commonly used medicine in clinical therapy of eye disorders in traditional Chinese medicine (TCM). In recent years, it is also used for treating DR, but the specific mechanism is unclear. Therefore, this study explores the potential mechanism of AM in DR treatment by using network pharmacology. Methods Based on the oral bioavailability (OB) and drug likeness (DL) of two ADME (absorption, distribution, metabolism, excretion) parameters, Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), Swiss Target Prediction platform, GeneCards, and OMIM database were used to predict and screen the active compounds of AM, the core targets of AM in DR treatment. The Metascape data platform was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the core targets. Results 24 active compounds were obtained, such as quercetin, kaempferol, and astragaloside IV. There were 169 effective targets of AM in DR treatment, and the targets were further screened and finally, 38 core targets were obtained, such as VEGFA, AKT1, and IL-6. EGFR tyrosine kinase inhibitor resistance, AGE-RAGE signaling pathway in diabetic complications, PI3K-Akt signaling pathway, and other metabolic pathways participated in oxidative stress, cell apoptosis, angiogenesis signal transduction, inflammation, and other biological processes. Conclusion AM treats DR through multiple compounds, multiple targets, and multiple pathways. AM may play a role in the treatment of DR by targeting VEGFA, AKT1, and IL-6 and participating in oxidative stress, angiogenesis, and inflammation.

Evidence-Based Guidelines for Management of Diabetic Macular Edema

Purpose: The purpose of this article is to provide a data-driven set of best practices to consider in the management of diabetic macular edema (DME). Methods: The current discussion and recommendations represent the authors’ interpretations of data from selected references based on perceived relevance and study design. Results: DME is a common cause of visual impairment globally. The underlying progressive retinal microvascular damage is associated with upregulation of VEGF and a multitude of other inflammatory pathways. Three clinically relevant subcategories of DME can be identified: central-involved DME (CIDME) with preserved visual acuity, CIDME with associated visual loss, and non-CIDME. Management approaches may include observation, laser photocoagulation, intravitreal pharmacotherapy with anti-VEGF agents or corticosteroids, or a combination of these, and may vary depending on the specific type of DME and associated severity of diabetic retinopathy. Additional factors to consider in the management of patients with DME include the appropriate use of imaging and recognition of the chronic nature of the underlying disease process in many eyes. Conclusions: DME management is complex. Intravitreal pharmacotherapies are the current cornerstone of treatment for CIDME and appear poised to remain so for the foreseeable future.

Retinal microvascular damage and nocturnal hypertension: Therapeutic targets to bear in mind

Retinal microvascular damage and nocturnal hypertension: Therapeutic targets to bear in mind