Jagged1-Notch1 Signaling Pathway Induces M1 Microglia to Disrupt the Barrier Function of Retinal Microvascular Endothelial Cells.

PURPOSE: Microglia-related inflammation is closely linked to the pathogenesis of retinal diseases. The primary objective of this research was to investigate the impact and mechanism of M1 phenotype microglia on the barrier function of retina microvascular endothelial cells. METHODS: Quantitative polymerase chain reactions and western blot techniques were utilized to analysis the mRNA and protein expressions of M1 and M2 markers of human microglial clone 3 cell line (HMC3), as well as the levels of Notch ligands and receptors under the intervention of lipopolysaccharide (LPS) or interleukin (IL)-4. ELISA was utilized to detect the pro-inflammatory and anti-inflammatory cytokines from HMC3 cells. The cellular tight junction and apoptosis of human retinal microvascular endothelial cells (HRMECs) were assessed by western blot and fluorescein isothiocyanate-dextran permeability assay. The inhibitors of Notch1 and RNA interference (RNAi) targeting Jagged1 were used to assess their contribution to the barrier function of vascular endothelial cells. RESULTS: Inducible nitric oxide synthase (iNOS) and IL-1ß were considerably elevated in LPS-treated HMC3, while CD206 and Arg-1 markedly elevated under IL-4 stimulation. The conditioned medium derived from LPS-treated HMC3 cells promoted permeability, diminished the expression of zonula occludens-1 and Occludin, and elevated the expression of Cleaved caspase-3 in HRMECs. RNAi targeting Jagged1 or Notch1 inhibitor could block M1 HMC3 polarization and maintain barrier function of HRMECs. CONCLUSION: Our findings suggest that Jagged1-Notch1 signaling pathway induces M1 microglial cells to disrupt the barrier function of HRMECs, which may lead to retinal diseases.

Targeting pathogenic CD8+ tissue-resident T cells with chimeric antigen receptor therapy in murine autoimmune cholangitis.

Primary biliary cholangitis (PBC) is a cholestatic autoimmune liver disease characterized by autoreactive T cell response against intrahepatic small bile ducts. Here, we use Il12b-/-Il2ra-/- mice (DKO mice) as a model of autoimmune cholangitis and demonstrate that Cd8a knockout or treatment with an anti-CD8α antibody prevents/reduces biliary immunopathology. Using single-cell RNA sequencing analysis, we identified CD8+ tissue-resident memory T (Trm) cells in the livers of DKO mice, which highly express activation- and cytotoxicity-associated markers and induce apoptosis of bile duct epithelial cells. Liver CD8+ Trm cells also upregulate the expression of several immune checkpoint molecules, including PD-1. We describe the development of a chimeric antigen receptor to target PD-1-expressing CD8+ Trm cells. Treatment of DKO mice with PD-1-targeting CAR-T cells selectively depleted liver CD8+ Trm cells and alleviated autoimmune cholangitis. Our work highlights the pathogenic role of CD8+ Trm cells and the potential therapeutic usage of PD-1-targeting CAR-T cells.

Construction of Imidazole-Fused-Ring Systems by Iron-Catalyzed C(sp3)-H Amination-Cyclization under Aerobic Conditions.

An iron-catalyzed efficient C-H amination for the construction of imidazole-fused-ring systems was developed under aerobic conditions. Compared to previous studies, this work exhibited green features. The reaction was conducted in the green solvent anisole, with water as the only byproduct. Four C(sp3)-H bonds were cleaved and three C-N bonds were formed in this transformation. Imidazo[1,5-a]pyridine-, imidazo[5,1-b]oxazole-, imidazo[5,1-b]thiazole-, imidazo[1,5-a]pyrazine-, and imidazo[1,5-a]imidazole-related N-heterocycles were obtained in acceptable-to-excellent yield.

Associations of concomitant retinopathy and depression with mortality in a nationally representative population.

OBJECTIVE: To evaluate the interaction effects between retinopathy and depression on mortality risks in genral population and subpopulation with diabetes. METHODS: Prospective analyses were conducted on data from the National Health and Nutrition Examination Surveys study. Associations of retinopathy, depression and their interaction with all-cause, cardiovascular disease (CVD)-specific, cancer-specific and other-specific mortality risk were estimated using Kaplan-Meier curves and multivariate Cox proportional hazards models. RESULTS: Among 5367 participants, the weighted prevalence of retinopathy and depression was 9.6 % and 7.1 %, respectively. After a follow-up period of 12.1 years, 1295 deaths (17.3 %) occurred. Retinopathy was associated with an increased risk of all-cause (hazard ratio [HR]; 95 % confidence interval [CI]) (1.47; 1.27-1.71), CVD-specific (1.87; 1.45-2.41), and other-specific (1.43; 1.14-1.79) mortality. Similar relationship was observed between depression and all-cause mortality (1.24; 1.02-1.52). Retinopathy and depression had a positive multiplicative and additive interaction effect on all-cause (Pinteraction = 0.015; relative excess risk of interaction [RERI] 1.30; 95 % CI 0.15-2.45) and CVD-specific mortality (Pinteraction = 0.042; RERI 2.65; 95 % CI -0.12-5.42). Concomitant retinopathy and depression was more markedly associated with all-cause (2.86; 1.91-4.28), CVD-specific (4.70; 2.57-8.62), and other-specific mortality risks (2.18; 1.14-4.15) compared to those without retinopathy and depression. These associations were more pronounced in the diabetic participants. CONCLUSIONS: The co-occurrence of retinopathy and depression increases the risk of all-cause and CVD-specific mortality among middle-aged and older adults in the United States, especially in population with diabetes. Focus on diabetic patients and active evaluation and intervention of retinopathy with depression may improve their quality of life and mortality outcomes.

A specialized channel for encoding auditory transients in the magnocellular division of the human medial geniculate nucleus.

We test the hypothesis that there exists a generalized magnocellular system in the brain optimized for temporal processing. In the visual system, it is well known that the magnocellular layers in the lateral geniculate nucleus (LGN) are strongly activated by transients and quickly habituate. However, little is known about the perhaps analogous magnocellular division of the medial geniculate nucleus (MGN), the auditory relay in the thalamus. We measured the functional responses of the MGN in 11 subjects who passively listened to sustained and transient nonlinguistic sounds, using functional MRI. We observed that voxels in the ventromedial portion of the MGN, corresponding to the magnocellular division, exhibited a robust preference to transient sounds, consistently across subjects, whereas the remainder of the MGN did not discriminate between sustained and transient sounds. We conclude that the magnocellular neurons in the MGN parallel the magnocellular neurons in its visual counterpart, LGN, and constitute an information stream specialized for encoding auditory dynamics.

A clickable photoaffinity probe of betulinic acid identifies tropomyosin as a target.

Target identification of bioactive compounds is important for understanding their mechanisms of action and provides critical insights into their therapeutic utility. While it remains a challenge, unbiased chemoproteomics strategy using clickable photoaffinity probes is a useful and validated approach for target identification. One major limitation of this approach is the efficient synthesis of appropriately substituted clickable photoaffinity probes. Herein, we describe an efficient and consistent method to prepare such probes. We further employed this method to prepare a highly stereo-congested probe based on naturally occurring triterpenoid betulinic acid. With this photoaffinity probe, we identified tropomyosin as a novel target for betulinic acid that can account for the unique biological phenotype on cellular cytoskeleton induced by betulinic acid.

A MULTITASK DEEP-LEARNING SYSTEM FOR ASSESSMENT OF DIABETIC MACULAR ISCHEMIA ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IMAGES.

PURPOSE: We aimed to develop and test a deep-learning system to perform image quality and diabetic macular ischemia (DMI) assessment on optical coherence tomography angiography (OCTA) images. METHODS: This study included 7,194 OCTA images with diabetes mellitus for training and primary validation and 960 images from three independent data sets for external testing. A trinary classification for image quality assessment and the presence or absence of DMI for DMI assessment were labeled on all OCTA images. Two DenseNet-161 models were built for both tasks for OCTA images of superficial and deep capillary plexuses, respectively. External testing was performed on three unseen data sets in which one data set using the same model of OCTA device as of the primary data set and two data sets using another brand of OCTA device. We assessed the performance by using the area under the receiver operating characteristic curves with sensitivities, specificities, and accuracies and the area under the precision-recall curves with precision. RESULTS: For the image quality assessment, analyses for gradability and measurability assessment were performed. Our deep-learning system achieved the area under the receiver operating characteristic curves >0.948 and area under the precision-recall curves >0.866 for the gradability assessment, area under the receiver operating characteristic curves >0.960 and area under the precision-recall curves >0.822 for the measurability assessment, and area under the receiver operating characteristic curves >0.939 and area under the precision-recall curves >0.899 for the DMI assessment across three external validation data sets. Grad-CAM demonstrated the capability of our deep-learning system paying attention to regions related to DMI identification. CONCLUSION: Our proposed multitask deep-learning system might facilitate the development of a simplified assessment of DMI on OCTA images among individuals with diabetes mellitus at high risk for visual loss.

High HDL-C and high LDL-C are risk factors of pterygium in a population-based cross-sectional study in Southern China: the Dongguan Eye Study.

OBJECTIVES: To investigate the relationship between serum lipids and pterygium in a large-scale rural population aged 40 years or older from Southern China. STUDY DESIGN: The Dongguan Eye Study was a cross-sectional population-based study from September 2011 to February 2012. SETTING: The area was set in the rural area of Dongguan, Southern China. PARTICIPANTS: Adult rural population aged 40 or older. METHODS: Participants underwent physical, haematological and ophthalmic examinations. PRIMARY AND SECONDARY OUTCOME MEASURES: The frequency and risk factors of pterygium. RESULTS: A total of 11 357 participants were eligible for inclusion and 8952 (78.8%) participants were enrolled for the systemic and ophthalmic examinations. The prevalence of pterygium was 17.3% after adjusting the sex and age distribution, 22.0% in participants with hypercholesterolaemia (total cholesterol ≥6.22 mmol/L (240 mg/dL)) and 21.8% in those with low-density lipoprotein-cholesterol (LDL-C) ≥4.14 mmol/L (160 mg/dL), respectively. After adjusting for multiple confounding factors, higher level of high-density lipoprotein-cholesterol (HDL-C) (OR: 1.23, 95% CI: 1.06 to 1.41) and LDL-C (OR: 1.13, 95% CI: 1.06 to 1.20) were positively associated with the risk of pterygium. The ORs for HDL-C or LDL-C with pterygium were significantly greater in participants aged 40-49 years than those aged 50 years or above (P for interaction <0.001). Furthermore, increased HDL-C showed greater association with pterygium in normal body mass index (BMI) group compared with overweight group (P for interaction=0.002). CONCLUSION: Increased HDL-C and LDL-C are risk factors of pterygium, especially in people <50 years or those with normal BMI level. Strict control of HDL-C and LDL-C may be a new prevention method in reducing the risk of pterygium.

Long-Term Retinal Neurovascular and Choroidal Changes After Panretinal Photocoagulation in Diabetic Retinopathy.

Purpose: To evaluate the long-term retinal microvascular, neural, and choroidal changes in the patients with severe nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) following panretinal photocoagulation (PRP). Methods: Forty-five eyes of 28 patients with treatment-naive severe NPDR and PDR were included and followed for 12 months after PRP. Microvascular and neural changes in the macular and peripapillary areas were assessed by using optical coherence tomography angiography. Subfoveal choroidal thickness (SFCT) was measured by using optical coherence tomography. A Linear mixed-effects model was used to highlight the differences for the variables after adjusting for sex, age, and axial length. Results: Compared to baseline, there were no statistical differences in the best corrected visual acuity (BCVA), macular and peripapillary vessel density (VD), and SFCT following PRP. Macular thickness significantly increased at 1 and 3-6 months after PRP (p < 0.05), while the peripapillary retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness significantly increased at 1 month postoperatively (p < 0.01). Global loss volume and focal loss volume significantly decreased at the same time point (p < 0.05). Conclusion: The unchanged BCVA, VD, the thickness of RNFL and GCC, and SFCT during the 12-month follow-up period suggest that PRP may prevent the retinal neurovascular and choroidal damage.

Cytoskeleton-associated protein 2 (CKAP2) is regulated by vascular endothelial growth factor and p53 in retinal capillary endothelial cells under high-glucose conditions.

PURPOSE: We previously found the mutation frequency of cytoskeleton-associated protein 2 (CKAP2) was significantly increased in proliferative diabetic retinopathy (PDR) patients through whole exome sequencing. The present study was conducted to explore the expression and possible mechanism of CKAP2 in PDR patients and human retinal capillary endothelial cells (HRCECs) under high-glucose (HG) conditions. METHODS: Expression of CKAP2 and p53 in the vitreous fluid and fibrovascular membrane (FVM) of PDR patients and HRCECs under HG conditions was observed. Cell proliferation, migration and tubule formation were assessed. Ranibizumab and siRNA transfection were used in the inhibition assay. RESULTS: CKAP2 and p53 were significantly increased in the ocular tissues of PDR patients. HG combined with VEGF treatment significantly up-regulated expression of CKAP2 and p53 in HRCECs. Inhibition of CKAP2 attenuated the abilities of cell proliferation, migration and tube formation under HG conditions. Blocking VEGF or p53 significantly decreased CKAP2 expression, whereas inhibition of CKAP2 failed to alter the level of VEGF or p53. CONCLUSIONS: CKAP2 is involved in the pathogenesis of PDR and regulated by VEGF and p53 under HG conditions.

VDAC1 regulates mitophagy in NLRP3 inflammasome activation in retinal capillary endothelial cells under high-glucose conditions.

Diabetic retinopathy (DR) has been considered to involve mitochondrial alterations and be related to the nucleotide-binding oligomerization domain-like receptors 3 (NLRP3) inflammasome activation. The voltage-dependent anion channel 1 (VDAC1) protein is one of the key proteins that regulates the metabolic and energetic functions of the mitochondria. To explore the involvement of VDAC1 in mitophagy regulation of NLRP3 inflammasome activation under high-glucose (HG) conditions, this study examined expressions of VDAC1, mitochondrial function and mitophagy-related proteins, and NLRP3 inflammasome-related proteins in human retinal capillary endothelial cells (HRCECs) cultured with 30 mM of glucose in the presence or absence of mitophagy inhibitor (Mdivi-1) using Western blot. Mitochondrial membrane potential and mitochondrial reactive oxygen species (mtROS) were detected using flow cytometry. GFP-tagged pAdTrack-VDAC1 adenovirus was used to overexpress VDAC1. Cell biological behaviors, including proliferation, migration, tubule formation, and apoptosis, were also observed. Our results showed that when compared to the normal glucose and high mannitol groups, increased amounts of mitochondrial fragments, reduced mitochondrial membrane potential, increased expression of mitochondrial fission protein Drp 1, decreased expression of mitochondrial fusion protein Mfn 2, accumulation of mtROS, and activation of the NLRP3 inflammasome were observed in the HG group. Meanwhile, HG markedly reduced the protein expressions of PINK1, Parkin and VDAC1. Inhibition of mitophagy reduced PINK1 expression, enhanced NLRP3 expression, but failed to alter VDAC1. VDAC1 overexpression promoted PINK1 expression, inhibited NLRP3 activation and changed the cell biological behaviors under HG conditions. These findings demonstrate that VDAC1-mediated mitophagy plays a crucial role in regulating NLRP3 inflammasome activation in retinal capillary endothelial cells under HG conditions, suggesting that VDAC1 may be a potential target for preventing or treating DR.

Usefulness of Machine Learning for Identification of Referable Diabetic Retinopathy in a Large-Scale Population-Based Study.

Purpose: To development and validation of machine learning-based classifiers based on simple non-ocular metrics for detecting referable diabetic retinopathy (RDR) in a large-scale Chinese population-based survey. Methods: The 1,418 patients with diabetes mellitus from 8,952 rural residents screened in the population-based Dongguan Eye Study were used for model development and validation. Eight algorithms [extreme gradient boosting (XGBoost), random forest, naïve Bayes, k-nearest neighbor (KNN), AdaBoost, Light GBM, artificial neural network (ANN), and logistic regression] were used for modeling to detect RDR in individuals with diabetes. The area under the receiver operating characteristic curve (AUC) and their 95% confidential interval (95% CI) were estimated using five-fold cross-validation as well as an 80:20 ratio of training and validation. Results: The 10 most important features in machine learning models were duration of diabetes, HbA1c, systolic blood pressure, triglyceride, body mass index, serum creatine, age, educational level, duration of hypertension, and income level. Based on these top 10 variables, the XGBoost model achieved the best discriminative performance, with an AUC of 0.816 (95%CI: 0.812, 0.820). The AUCs for logistic regression, AdaBoost, naïve Bayes, and Random forest were 0.766 (95%CI: 0.756, 0.776), 0.754 (95%CI: 0.744, 0.764), 0.753 (95%CI: 0.743, 0.763), and 0.705 (95%CI: 0.697, 0.713), respectively. Conclusions: A machine learning-based classifier that used 10 easily obtained non-ocular variables was able to effectively detect RDR patients. The importance scores of the variables provide insight to prevent the occurrence of RDR. Screening RDR with machine learning provides a useful complementary tool for clinical practice in resource-poor areas with limited ophthalmic infrastructure.

Differential distribution of manifest lesions in diabetic retinopathy by fundus fluorescein angiography and fundus photography.

BACKGROUND: To analyze the distribution of manifest lesions of diabetic retinopathy (DR) by fundus fluorescein angiography (FFA) and color fundus photography (FP). METHODS: A total of 566 eyes of 324 Chinese patients diagnosed with DR were included in this retrospective study. DR severity was graded by the international grading criterion. The distributions of microaneurysms (MA), intraretinal hemorrhages/exudates (He/Ex), intraretinal microvascular abnormality (IRMA), capillary nonperfusion areas (NPA), and neovascularization (NV) were estimated by multiple logistic regression analyse based on nine-field FFA and FP images. RESULTS: In mild nonproliferative diabetic retinopathy (NPDR), the highest frequency of MA was found in the posterior pole (67.7%), followed by the inferior nasal (59.4%), and the nasal (55.4%) fields. In moderate NPDR, MA frequently distributed in the posterior pole (98.0%), nasal (97.0%), superior (96.0%), inferior nasal (94.9%), and inferior (92.9%) fields, whereas He/Ex were most prevalent in the posterior pole (69.7%). In severe NPDR and proliferative DR, IRMA, NPA, and NV were more frequent in the nasal field, particularly in the inferior nasal field (60.3, 38.7, and 76.0%, respectively). All lesions were more observed in the combined posterior pole, nasal, and inferior nasal fields than in the posterior pole or combined two fields in the early and severe stages of DR (P < 0.05). CONCLUSIONS: The manifest lesions of DR were common in the nasal field besides the posterior pole in Chinese patients. A combined examination of the posterior pole, nasal, and inferior nasal mid-peripheral retina would help to detect different retinal lesions of DR. TRIAL REGISTRATION: ClinicalTrial. gov, NCT03528720 . Registered 18 May 2018 - Retrospectively registered.

Identifying Microvascular and Neural Parameters Related to the Severity of Diabetic Retinopathy Using Optical Coherence Tomography Angiography.

Purpose: To identify microvascular and neural parameters related to the severity of diabetic retinopathy (DR) by using optical coherence tomography angiography in patients with type 2 diabetes. Methods: This cross-sectional study included 110 eyes (63 patients) with no DR, 46 eyes (33 patients) with mild nonproliferative DR, 36 eyes (23 patients) with moderate nonproliferative DR, 36 eyes (22 patients) with severe nonproliferative DR, and 31 eyes (19 patients) with proliferative DR. The optical coherence tomography angiography images were processed to quantify the foveal avascular zone parameters, macular vessel density (VD), retinal thickness, peripapillary VD, retinal nerve fiber layer thickness, and ganglion cell complex thickness. A LASSO-based continuation ratio model was used to select the most clinically relevant parameters for predicting the stage of DR. Results: The regression model identified a set of regional parameters for each scanning pattern that identified the DR severity, including foveal avascular zone perimeter; FD-300; temporal perifoveal superficial capillary plexus VD and retinal thickness; temporal and nasal parafoveal deep capillary plexus VD; peripapillary VD in the temporal superior, nasal inferior, and temporal inferior sectors; temporal superior and nasal inferior retinal nerve fiber layer thickness; ganglion cell complex thickness; and FLV, which changed significantly with the progression of DR. Furthermore, two combined blocks exhibited different sensitive parameters to differentiate between the groups based on DR severity. Similar results were obtained in eyes without diabetic macular edema. Conclusions: We identified microvascular and neural parameters related to the severity of DR using optical coherence tomography angiography, suggesting their potential clinical application for better screening and staging of DR.

Is kidney function associated with primary open-angle glaucoma? Findings from the Asian Eye Epidemiology Consortium.

AIM: To comprehensively examine the association between kidney function and primary open angle glaucoma (POAG) in a large consortium of multiple Asian population-based studies. METHODS: 28 925 participants (57 340 eyes) from 9 population-based studies (from China, Hong Kong, India, Korea, Russia, Singapore) of the Asian Eye Epidemiology Consortium were included. Across all studies, POAG was defined based on the International Society of Geographical and Epidemiological Ophthalmology criteria. Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine. Chronic kidney disease (CKD) was defined as eGFR<60 mL/min/1.73 m2. Eye-specific data were pooled from each study. Multivariable regression analysis with generalised estimating equation models was performed to evaluate the associations between kidney function with POAG and intraocular pressure (IOP). RESULTS: After adjusting for age, gender, study group, hypertension, diabetes, hyperlipidaemia, body mass index, smoking status and IOP, lower eGFR (per 10 mL/min/1.73 m2 decrease) was not significantly associated with POAG (OR=1.01; p=0.77). Presence of CKD was also not significantly associated with POAG (OR=1.01; p=0.739). Furthermore, lower eGFR and presence of CKD were not associated with IOP (all p≥0.12), However, in the subgroup of combined Korean and Chinese individuals, significant associations between lower eGFR (OR=1.09; 95% CI 1.00 to 1.18; p=0.048) and severe kidney function decline (<45 mL/min/1.73 m2; OR=2.57; 95% CI 1.34 to 4.93; p=0.004) with POAG, were observed. CONCLUSION: In this large pooled-analysis of multiple Asian population-based studies, our findings suggest that the association between CKD and POAG may only be present in East Asians specifically but not in the overall Asian population. Further evaluation in Japanese population is warranted to confirm this observation.

Prevalence and risk factors for diabetic retinopathy in a cross-sectional population-based study from rural southern China: Dongguan Eye Study.

RESEARCH QUESTION: The current population-based study aimed to investigate the prevalence of diabetic retinopathy (DR) and risk factors among residents over 40 years old in the rural area of Dongguan, southern China. STUDY DESIGN: The Dongguan Eye Study was a population-based study from September 2011 to February 2012. SETTING: The area was set in the rural area of Dongguan, southern China. PARTICIPANTS: Adult rural population aged 40 or older. INTERVENTION: Participants underwent haematological, physical, ophthalmic examinations and completed a questionnaire regarding lifestyles and systemic medical conditions. PRIMARY AND SECONDARY OUTCOME MEASURES: The frequency and risk factors of visual impairment and the major vision-threatening eye diseases. RESULTS: Of the 8952 Han Chinese, 1500 were diagnosed with type 2 diabetes mellitus (T2DM) with an average age of 59.5±11.1 years, and 1310 participants with fundus photography results were analysed. Standardised prevalence rate of DR was 18.2% for all patients with diabetes, 32.8% for the patients with previously diagnosed diabetes and 12.6% for newly diagnosed patients with T2DM. The prevalence rate of male DR was significantly higher than that of female DR (23.0% vs 14.1%, p<0.001). No significant difference was found in age-specific prevalence of DR. In diabetic patients, the prevalence rates of vision-threatening diabetic retinopathy, diabetic macular oedema and clinically significant macular oedema were 2.5%, 2.8% and 0.9%, respectively. Male gender, higher education level, longer duration of diabetes mellitus (DM), higher systolic blood pressure and glycosylated haemoglobin were independent risk factors for DR development in patients with diabetes. CONCLUSION: A relatively lower prevalence of DR was found among the participants with T2DM in residents over 40 years in the rural area of southern China. Thus, an ophthalmic examination is recommended, especially for individuals with DM and DR risk factors. There is a need to increase awareness and education on DM and DR, especially in subjects with DR risk factors to reduce the incidence of DR and macular oedema.

Macular Capillary Perfusion in Chinese Patients With Diabetic Retinopathy Obtained With Optical Coherence Tomography Angiography.

BACKGROUND AND OBJECTIVE: To compare the macular perfusion in the retina and choroidal layer between control subjects and Chinese patients with diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA) and to evaluate the association of OCTA characteristics with the stage of DR. PATIENTS AND METHODS: A total of 200 eyes (normal controls = 40; mild non-proliferative diabetic retinopathy [NPDR] = 40; moderate NPDR = 40; severe NPDR = 40; and PDR [proliferative diabetic retinopathy] = 40) underwent OCTA imaging. OCTA parameters were vessel densities in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris, as well as foveal avascular zone (FAZ) area (mm2) in the SCP. RESULTS: The reduction of macular perfusion in the SCP, DCP, and choriocapillaris was correlated with increasing severity of DR. Vessel density in the SCP, DCP, and choriocapillaris was 55.31% ± 2.56%, 62.40% ± 2.46%, and 66.87% ± 1.30%, respectively, in control subjects; 50.58% ± 3.14%, 56.31% ± 4.24%, and 66.20% ± 1.69%, respectively, in mild NPDR; 46.46% ± 3.09%, 49.40% ± 5.68%, and 64.39% ± 1.94%, respectively, in moderate NPDR; 45.61% ± 3.81%, 49.33% ± 6.14%, and 63.75% ± 2.21%, respectively, in severe NPDR; and 43.78% ± 3.71%, 44.78% ± 6.36%, and 61.32% ± 6.29%, respectively, in PDR. Vessel density in DR groups decreased compared with normal controls (P < .001). FAZ area in the SCP was 0.34 ± 0.09 mm2 in control subjects compared with 0.48 ± 0.17 mm2 (mild NPDR), 0.52 ± 0.13 mm2 (moderate NPDR), 0.62 ± 0.24 mm2 (severe NPDR), and 0.75 ± 0.30 mm2 (PDR). FAZ in the SCP of patients with DR was greater than that in control subjects (P < .001). Vessel density in the DCP shows better ability to identify the severity of DR (area under the curve, sensitivity, and specificity of 0.967, 92.5%, and 93.1%, respectively) than vessel density in the SCP and choriocapillaris. CONCLUSION: OCTA might be clinically useful to evaluate different stages of DR in a noninvasive manner. Vessel density in DCP could be an objective and reliable indicator for monitoring progression of DR. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e88-e95.].

Synthesis, Characterization, and Evaluation of Near-IR Boron Dipyrromethene Bioconjugates for Labeling of Adenocarcinomas by Selectively Targeting the Epidermal Growth Factor Receptor.

A series of five boron dipyrromethene (BODIPY) bioconjugates containing an epidermal growth factor receptor (EGFR)-targeted pegylated LARLLT peptide and/or a glucose or biotin ethylene diamine group were synthesized, and the binding capability of the new conjugates to the extracellular domain of EGFR was investigated using molecular modeling, surface plasmon resonance, fluorescence microscopy, competitive binding assays, and animal studies. The BODIPY conjugates with a LARLLT peptide were found to bind specifically to EGFR, whereas those lacking the peptide bound weakly and nonspecifically. All BODIPY conjugates showed low cytotoxicity (IC50 > 94 µM) in HT-29 cells, both in the dark and upon light activation (1.5 J/cm2). Studies of nude mice bearing subcutaneous human HT-29 xenografts revealed that only BODIPY conjugates bearing the LARLLT peptide showed tumor localization 24 h after intravenous administration. The results of our studies demonstrate that BODIPY bioconjugates bearing the EGFR-targeting peptide 3PEG-LARLLT show promise as near-IR fluorescent imaging agents for colon cancers overexpressing EGFR.

Intraocular Pressure in General and Diabetic Populations From Southern China: the Dongguan Eye Study.

Purpose: To investigate the distribution and risk factors for intraocular pressure (IOP) among general and diabetic populations in Southern China. Methods: The study participants aged 40 years or older were enrolled from the Dongguan Eye Study, a population-based cross-sectional study from September 2011 to February 2012. Systemic and ophthalmic examinations were performed, and diabetes status was screened based on the American Diabetes Association diagnostic criteria (2010). IOP was measured by a noncontact tonometer per standardized protocol. Regression analyses were used to assess the association between potential risk factors and IOP. Results: A total of 2112 subjects were included with a median age of 55 years. IOP for general population showed a near normal distribution with an average of 15.58 ± 3.27 mm Hg. Multiple regression analyses revealed that higher IOP was significantly correlated with younger age, higher body mass index (BMI), shorter height, higher blood pressure (BP), higher fasting blood glucose (FBG), higher low-density lipoprotein cholesterol (LDL-C), lower high-density lipoprotein cholesterol (HDL-C), and thicker central corneal thickness (CCT). There was no association between diabetes status and IOP after adjusting for possible confounders. IOP for diabetic participants showed a right-skewed distribution. Risk factors for IOP elevation in diabetes included female, younger age, higher BP, higher LDL-C, lower HDL-C, and thicker CCT. Conclusions: The present study identifies risk factors for elevated IOP in general and diabetic populations. Younger age and lower HDL-C, as well as higher BP, LDL-C, and CCT were significant factors contributing to higher IOP, especially in the female diabetic population.