Adipose-derived stem cells promote glycolysis and peritoneal metastasis via TGF-ß1/SMAD3/ANGPTL4 axis in colorectal cancer.

Peritoneal metastasis, the third most common metastasis in colorectal cancer (CRC), has a poor prognosis for the rapid progression and limited therapeutic strategy. However, the molecular characteristics and pathogenesis of CRC peritoneal metastasis are poorly understood. Here, we aimed to elucidate the action and mechanism of adipose-derived stem cells (ADSCs), a prominent component of the peritoneal microenvironment, in CRC peritoneal metastasis formation. Database analysis indicated that ADSCs infiltration was increased in CRC peritoneal metastases, and high expression levels of ADSCs marker genes predicted a poor prognosis. Then we investigated the effect of ADSCs on CRC cells in vitro and in vivo. The results revealed that CRC cells co-cultured with ADSCs exhibited stronger metastatic property and anoikis resistance, and ADSCs boosted the intraperitoneal seeding of CRC cells. Furthermore, RNA sequencing was carried out to identify the key target gene, angiopoietin like 4 (ANGPTL4), which was upregulated in CRC specimens, especially in peritoneal metastases. Mechanistically, TGF-ß1 secreted by ADSCs activated SMAD3 in CRC cells, and chromatin immunoprecipitation assay showed that SMAD3 facilitated ANGPTL4 transcription by directly binding to ANGPTL4 promoter. The ANGPTL4 upregulation was essential for ADSCs to promote glycolysis and anoikis resistance in CRC. Importantly, simultaneously targeting TGF-ß signaling and ANGPTL4 efficiently reduced intraperitoneal seeding in vivo. In conclusion, this study indicates that tumor-infiltrating ADSCs promote glycolysis and anoikis resistance in CRC cells and ultimately facilitate peritoneal metastasis via the TGF-ß1/SMAD3/ANGPTL4 axis. The dual-targeting of TGF-ß signaling and ANGPTL4 may be a feasible therapeutic strategy for CRC peritoneal metastasis.

The role of purinergic signaling in acupuncture-mediated relief of neuropathic and inflammatory pain.

Acupuncture is a traditional medicinal practice in China that has been increasingly recognized in other countries in recent decades. Notably, several reports have demonstrated that acupuncture can effectively aid in pain management. However, the analgesic mechanisms through which acupuncture provides such benefits remain poorly understood. Purinergic signaling, which is mediated by purine nucleotides and purinergic receptors, has been proposed to play a central role in acupuncture analgesia. On the one hand, acupuncture affects the transmission of nociception by increasing adenosine triphosphate dephosphorylation and thereby decreasing downstream P2X3, P2X4, and P2X7 receptors signaling activity, regulating the levels of inflammatory factors, neurotrophic factors, and synapsin I. On the other hand, acupuncture exerts analgesic effects by promoting the production of adenosine, enhancing the expression of downstream adenosine A1 and A2A receptors, and regulating downstream inflammatory factors or synaptic plasticity. Together, this systematic overview of the field provides a sound, evidence-based foundation for future research focused on the application of acupuncture as a means of relieving pain.

A Deep Learning Application of Capsule Endoscopic Gastric Structure Recognition Based on a Transformer Model.

BACKGROUND: Gastric structure recognition systems have become increasingly necessary for the accurate diagnosis of gastric lesions in capsule endoscopy. Deep learning, especially using transformer models, has shown great potential in the recognition of gastrointestinal (GI) images according to self-attention. This study aims to establish an identification model of capsule endoscopy gastric structures to improve the clinical applicability of deep learning to endoscopic image recognition. METHODS: A total of 3343 wireless capsule endoscopy videos collected at Nanfang Hospital between 2011 and 2021 were used for unsupervised pretraining, while 2433 were for training and 118 were for validation. Fifteen upper GI structures were selected for quantifying the examination quality. We also conducted a comparison of the classification performance between the artificial intelligence model and endoscopists by the accuracy, sensitivity, specificity, and positive and negative predictive values. RESULTS: The transformer-based AI model reached a relatively high level of diagnostic accuracy in gastric structure recognition. Regarding the performance of identifying 15 upper GI structures, the AI model achieved a macroaverage accuracy of 99.6% (95% CI: 99.5-99.7), a macroaverage sensitivity of 96.4% (95% CI: 95.3-97.5), and a macroaverage specificity of 99.8% (95% CI: 99.7-99.9) and achieved a high level of interobserver agreement with endoscopists. CONCLUSIONS: The transformer-based AI model can accurately evaluate the gastric structure information of capsule endoscopy with the same performance as that of endoscopists, which will provide tremendous help for doctors in making a diagnosis from a large number of images and improve the efficiency of examination.

Long-term surgical outcomes of combined Ahmed glaucoma valve implantation and phacoemulsification with intraocular lens implantation for patients with glaucoma secondary to iridocorneal endothelial syndrome.

BACKGROUND: To assess the long-term outcomes of patients with glaucoma secondary to iridocorneal endothelial syndrome (GS-ICE) who underwent Ahmed glaucoma valve (AGV) implantation combined with phacoemulsification and intraocular lens (IOL) implantation surgery. METHODS: In this non-comparative retrospective case series study, twelve patients with uncontrolled GS-ICE and cataract underwent Ahmed aqueous shunt combined with phacoemulsification and IOL implantation surgery at Beijing Tongren Eye Center between June 2014 and June 2022. Main medical records included best-corrected visual acuity (BCVA), intraocular pressure (IOP), number of antiglaucoma medications (AGM), corneal status and further surgical interventions. Surgical success was defined as a postoperative IOP ≥ 6mmHg and ≤ 21mmHg without (complete success) or with/without (qualified success) topical AGM and vision of at least light perception during the follow-up period. RESULTS: Twelve eyes of twelve patients were reviewed. Preoperative IOP was decreased from a mean of 38.5 ± 6.7 mmHg on 3.3 ± 0.9 AGM to a mean of 16.3 ± 4.3 mmHg (P<0.001) on 0.6 ± 1.1 medications (P<0.001) at the last follow-up (47.0 ± 24.7 months). Eight eyes (66.7%) had stable vision or at least one line improvement than that before surgery. Eight eyes (66.7%) achieved qualified success and six eyes (50.0%) achieved complete success after surgery. The surgical procedure had a qualified survival of 91.7% at 1 year, 82.5% at 3 years, 72.2% at 5 years, and 48.1% at 7 years. CONCLUSION: AGV implantation combined with phacoemulsification and IOL implantation seems to be an effective method in IOP control and vision maintain for patients with GS-ICE. The combined surgical procedure may be a reliable option for those GS-ICE patients with coexisting cataract.

The Impact of Parental Myopia and High Myopia on the Hyperopia Reserve of Preschool Children.

INTRODUCTION: The aim of this study was to explore the association between parental myopia and high myopia with children's refraction and ocular biometry in large-scale Chinese preschool children from the Beijing Hyperopia Reserve Study. SUBJECTS/METHODS: This cross-sectional kindergarten-based study enrolled children aged 3-6 years. Cycloplegic refraction, axial length (AL), and corneal radius (CR) were measured for all children. Parents were asked to complete a questionnaire about refractive status (no myopia, mild myopia <-3 D, moderate myopia ≥-3 D and ≤-6, and high myopia >-6 D). RESULTS: The study enrolled 2,053 children (1,069 boys and 984 girls), with a mean age of 4.26 ± 0.96 years and mean spherical equivalent refraction (SER) of 1.11 ± 0.97 diopter. Of the children, 90.7% had at least one myopic parent, and 511 children (24.9%) had at least one highly myopic parent. SER decreased significantly with increasing severity of parental myopia (p < 0.001). Preschool children's myopia was independently associated with parental myopia (OR, 10.4 and 11.5 for one and two highly myopic parent[s]). Age (OR = 1.1), gender (OR = 1.7; girls as references), near work time (OR = 1.2), and both maternal (OR, 1.4 and 2.0 for moderate and high myopia) and paternal myopia (OR, 1.6 and 1.9 for moderate and high myopia) were independent risk factors for lacking hyperopia reserve. CONCLUSION: Severe parental myopia was associated with a lower SER, longer AL, and higher AL/CR ratio in preschool children. Parental myopia and near work may predispose children to faster elimination of hyperopia reserves before exposure to higher educational stress.

Circ-ZNF236 mediates stem cells from apical papilla differentiation by regulating LGR4-induced autophagy.

AIM: Human stem cells from the apical papilla (SCAPs) are an appealing stem cell source for tissue regeneration engineering. Circular RNAs (circRNAs) are known to exert pivotal regulatory functions in various cell differentiation processes, including osteogenesis of mesenchymal stem cells. However, few studies have shown the potential mechanism of circRNAs in the odonto/osteogenic differentiation of SCAPs. Herein, we identified a novel circRNA, circ-ZNF236 (hsa_circ_0000857) and found that it was remarkably upregulated during the SCAPs committed differentiation. Thus, in this study, we showed the significance of circ-ZNF236 in the odonto/osteogenic differentiation of SCAPs and its underlying regulatory mechanisms. METHODOLOGY: The circular structure of circ-ZNF236 was identified via Sanger sequencing, amplification of convergent and divergent primers. The proliferation of SCAPs was detected by CCK-8, flow cytometry analysis and EdU incorporation assay. Western blotting, qRT-PCR, Alkaline phosphatase (ALP) and Alizarin red staining (ARS) were performed to explore the regulatory effect of circ-ZNF236/miR-218-5p/LGR4 axis in the odonto/osteogenic differentiation of SCAPs in vitro. Fluorescence in situ hybridization, as well as dual-luciferase reporting assays, revealed that circ-ZNF236 binds to miR-218-5p. Transmission electron microscopy (TEM) and mRFP-GFP-LC3 lentivirus were performed to detect the activation of autophagy. RESULTS: Circ-ZNF236 was identified as a highly stable circRNA with a covalent closed loop structure. Circ-ZNF236 had no detectable influence on cell proliferation but positively regulated SCAPs odonto/osteogenic differentiation. Furthermore, circ-ZNF236 was confirmed as a sponge of miR-218-5p in SCAPs, while miR-218-5p targets LGR4 mRNA at its 3'-UTR. Subsequent rescue experiments revealed that circ-ZNF236 regulates odonto/osteogenic differentiation by miR-218-5p/LGR4 in SCAPs. Importantly, circ-ZNF236 activated autophagy, and the activation of autophagy strengthened the committed differentiation capability of SCAPs. Subsequently, in vivo experiments showed that SCAPs overexpressing circ-ZNF236 promoted bone formation in a rat skull defect model. CONCLUSIONS: Circ-ZNF236 could activate autophagy through increasing LGR4 expression, thus positively regulating SCAPs odonto/osteogenic differentiation. Our findings suggested that circ-ZNF236 might represent a novel therapeutic target to prompt the odonto/osteogenic differentiation of SCAPs.

Enzyme-Mediated Proximity Labeling Identifies Small RNAs in the Endoplasmic Reticulum Lumen.

In eukaryotic cells, the subcellular targeting of RNA controls many fundamental aspects of cellular physiology. Despite broad distributions throughout the cytoplasm, RNA molecules are conventionally believed to be excluded from the secretory pathway compartments including the endoplasmic reticulum (ER). Recent discovery of RNA N-glycan modification (glycoRNAs) has challenged this view, but direct evidence of RNA localization in the ER lumen has been lacking. In this study, we applied enzyme-mediated proximity labeling to profile the ER lumen-localized RNAs in human embryonic kidney 293T cells and rat cortical neurons. Our data set reveals the presence of small non-coding RNAs in the ER lumen, including U RNAs and Y RNAs, which raises interesting questions regarding their transport mechanism and biological functions in the ER.

Mechanisms of acupuncture-electroacupuncture on inflammatory pain.

Acupuncture, as a traditional treatment, has been extensively used in China for thousands of years. According to the World Health Organization (WHO), acupuncture is recommended for the treatment of 77 diseases. And 16 of these diseases are related to inflammatory pain. As a combination of traditional acupuncture and modern electrotherapy, electroacupuncture (EA) has satisfactory analgesic effects on various acute and chronic pain. Because of its good analgesic effects and no side effects, acupuncture has been widely accepted all over the world. Despite the increase in the number of studies, the mechanisms via which acupuncture exerts its analgesic effects have not been conclusively established. A literature review of related research is of great significance to elaborate on its mechanisms and to inform on further research directions. We elucidated on its mechanisms of action on inflammatory pain from two levels: peripheral and central. It includes the mechanisms of acupuncture in the periphery (immune cells and neurons, purinergic pathway, nociceptive ion channel, cannabinoid receptor and endogenous opioid peptide system) and central nervous system (TPRV1, glutamate and its receptors, glial cells, GABAergic interneurons and signaling molecules). In this review, we collected relevant recent studies to systematically explain the mechanisms of acupuncture in treating inflammatory pain, with a view to providing direction for future applications of acupuncture in inflammatory pain and promoting clinical development.

Photocatalytic Proximity Labeling for Profiling the Subcellular Organization of Biomolecules.

Investigating the subcellular organization of biomolecules is important for understanding their biological functions. Over the past decade, proximity-dependent labeling methods have emerged as powerful tools for mapping biomolecules in their native context. These methods often capitalize on the in-situ generation of highly reactive intermediates for covalently tagging biomolecules located within nanometers to sub-micrometers of the source of labeling. Among these, photocatalytic proximity labeling methods achieve precise spatial and temporal control of labeling with visible light illumination. In this review, we summarize the mechanisms and applications of existing photocatalytic proximity labeling methods and discuss future opportunities for improving the method.

Adenosine signaling mediate pain transmission in the central nervous system.

Pain is a common clinical symptom that seriously affects the quality of life in a variety of patient populations. In recent years, research on the role of adenosine signaling in pain modulation has made great progress. Adenosine is a purine nucleoside and a neuromodulator, and regulates multiple physiological and pathophysiological functions through the activation of four G protein-coupled receptors, which are classified as A1, A2A, A2B, and A3 adenosine receptors (ARs). Adenosine and its receptors that are widespread in the central nervous system (CNS) play an important role in the processing of nociceptive sensory signals in different pain models. A1Rs have the highest affinity to adenosine, and the role in analgesia has been well investigated. The roles of A2ARs and A2BRs in the modulation of pain are controversial because they have both analgesic and pronociceptive effects. The analgesic effects of A3Rs are primarily manifested in neuropathic pain. In this article, we have reviewed the recent studies on ARs in the modulation of neuropathic pain, inflammatory pain, postoperative pain, and visceral pain in the CNS. Furthermore, we have outlined the pathways through which ARs contribute to pain regulation, thereby shedding light on how this mechanism can be targeted to provide effective pain relief.

SHED-derived exosomes attenuate trigeminal neuralgia after CCI of the infraorbital nerve in mice via the miR-24-3p/IL-1R1/p-p38 MAPK pathway.

BACKGROUND: Microglial activation in the spinal trigeminal nucleus (STN) plays a crucial role in the development of trigeminal neuralgia (TN). The involvement of adenosine monophosphate-activated protein kinase (AMPK) and N-methyl-D-aspartate receptor 1 (NMDAR1, NR1) in TN has been established. Initial evidence suggests that stem cells from human exfoliated deciduous teeth (SHED) have a potential therapeutic effect in attenuating TN. In this study, we propose that SHED-derived exosomes (SHED-Exos) may alleviate TN by inhibiting microglial activation. This study sought to assess the curative effect of SHED-Exos administrated through the tail vein on a unilateral infraorbital nerve chronic constriction injury (CCI-ION) model in mice to reveal the role of SHED-Exos in TN and further clarify the potential mechanism. RESULTS: Animals subjected to CCI-ION were administered SHED-Exos extracted by differential ultracentrifugation. SHED-Exos significantly alleviated TN in CCI mice (increasing the mechanical threshold and reducing p-NR1) and suppressed microglial activation (indicated by the levels of TNF-α, IL-1ß and IBA-1, as well as p-AMPK) in vivo and in vitro. Notably, SHED-Exos worked in a concentration dependent manner. Mechanistically, miR-24-3p-upregulated SHED-Exos exerted a more significant effect, while miR-24-3p-inhibited SHED-Exos had a weakened effect. Bioinformatics analysis and luciferase reporter assays were utilized for target gene prediction and verification between miR-24-3p and IL1R1. Moreover, miR-24-3p targeted the IL1R1/p-p38 MAPK pathway in microglia was increased in CCI mice, and participated in microglial activation in the STN. CONCLUSIONS: miR-24-3p-encapsulated SHED-Exos attenuated TN by suppressing microglial activation in the STN of CCI mice. Mechanistically, miR-24-3p blocked p-p38 MAPK signaling by targeting IL1R1. Theoretically, targeted delivery of miR-24-3p may offer a potential strategy for TN.

Incidental detection of retinoblastoma from accidental trauma in children.

BACKGROUND: To report a case series of patients who were diagnosed with retinoblastoma (RB), which was preceded by trauma, in a large multicenter cohort and to investigate the incidence, clinical characteristics, and causes of RB misdiagnosis. METHODS: The medical records of consecutive patients with RB between 2006 and 2015 were retrospectively reviewed. Characteristics of trauma patients, including their age at initial trauma, site of trauma, sex, and RB laterality, were analyzed. RESULTS: Among 3780 patients, 30 (0.8%) experienced systemic or ocular trauma prior to the detection of RB. The median age was 20.7 months, and the median follow-up time was 6 years. There were 2 eyes in stage A, 2 in stage B, 3 in stage C, 12 in stage D, and 15 in stage E. The remaining 2 eyes had extraocular RB. A total of 20 patients experienced ocular trauma, 9 patients experienced head trauma, and 1 patient experienced trauma in other body parts. RB was suspected or detected in 22 patients (73.3%) at the time of primary trauma occurrence, and 8 patients (26.7%) were misdiagnosed with RB during their first visit. Among them, all experienced blunt ocular trauma, and enucleation was performed in 7 patients in which 1 patient died. CONCLUSIONS: Less than 1% of the patients experienced systemic or ocular trauma before RB was detected. The majority were unilateral and in advanced stages. Differential diagnoses that are not trauma-related must always be considered, and comprehensive examinations must be conducted before diagnostic and therapeutic intraocular procedures are initiated.

Inhibition of PFKFB3 in HER2-positive gastric cancer improves sensitivity to trastuzumab by inducing tumour vessel normalisation.

BACKGROUND: Multiple mechanisms have been proposed that lead to reduced effectiveness of trastuzumab in HER2-positive gastric cancer (GC), yet resistance to trastuzumab remains a challenge in clinics. METHODS: We established trastuzumab-resistant cells and patient-derived xenografts models to measure metabolic levels and vascular density and shape. The HER2-positive GC patient samples were used to determine clinical significance. We also measured protein expression and phosphorylation modifications to determine those alterations related to resistance. In vivo studies combining inhibitor of PFKFB3 with trastuzumab corroborated the in vitro findings. RESULTS: The 6-phosphofructo-2-kinase (PFKFB3)-mediated trastuzumab resistance pathways in HER2-positive GC by activating the glycolytic pathway. We also found vessels are chaotic and destabilised in the tumour during the trastuzumab resistance process. Inhibition of PFKFB3 significantly diminished tumour proliferation and promoted vessel normalisation in the patient-derived xenograft model. Mechanistically, PFKFB3 promoted the secretion of CXCL8 into the tumour microenvironment, and phosphorylated Ser1151 of ERBB2, enhancing the transcription of CXCL8 by activating the PI3K/AKT/NFκB p65 pathway. CONCLUSIONS: Our current findings discover that PFKFB3 inhibitors might be effective tools to overcome adjuvant therapy resistance in HER2-positive GC and reshaping the microenvironment by normalising tumour vessels is a novel strategy to overcome trastuzumab resistance.

Convolution neural network for the diagnosis of wireless capsule endoscopy: a systematic review and meta-analysis.

BACKGROUND: Wireless capsule endoscopy (WCE) is considered to be a powerful instrument for the diagnosis of intestine diseases. Convolution neural network (CNN) is a type of artificial intelligence that has the potential to assist the detection of WCE images. We aimed to perform a systematic review of the current research progress to the CNN application in WCE. METHODS: A search in PubMed, SinoMed, and Web of Science was conducted to collect all original publications about CNN implementation in WCE. Assessment of the risk of bias was performed by Quality Assessment of Diagnostic Accuracy Studies-2 risk list. Pooled sensitivity and specificity were calculated by an exact binominal rendition of the bivariate mixed-effects regression model. I2 was used for the evaluation of heterogeneity. RESULTS: 16 articles with 23 independent studies were included. CNN application to WCE was divided into detection on erosion/ulcer, gastrointestinal bleeding (GI bleeding), and polyps/cancer. The pooled sensitivity of CNN for erosion/ulcer is 0.96 [95% CI 0.91, 0.98], for GI bleeding is 0.97 (95% CI 0.93-0.99), and for polyps/cancer is 0.97 (95% CI 0.82-0.99). The corresponding specificity of CNN for erosion/ulcer is 0.97 (95% CI 0.93-0.99), for GI bleeding is 1.00 (95% CI 0.99-1.00), and for polyps/cancer is 0.98 (95% CI 0.92-0.99). CONCLUSION: Based on our meta-analysis, CNN-dependent diagnosis of erosion/ulcer, GI bleeding, and polyps/cancer approached a high-level performance because of its high sensitivity and specificity. Therefore, future perspective, CNN has the potential to become an important assistant for the diagnosis of WCE.

Hospital-based study of risk factors associated with development of myopic macular neovascularization in highly myopic eyes.

INTRODUCTION: Myopic macular neovascularization (MNV) is the most common cause of a reduction of central vision in eyes with pathologic myopia, and it can progress to macular atrophy in the long-term. The aim of this study was to determine the risk factors associated with the development of MNVs. METHODS: There were 17,198 follow-up records from 5,409 eyes of 2,784 highly myopic patients that were reviewed. The general information and ophthalmic information in the records were studied. The significance of the correlations of factors associated with the development and predicting the development of myopic MNV were determined. RESULTS: Being a woman (odds ratio [OR]: 0.727, P<0.001), having a longer axial length (OR = 0.948, P<0.001), a poorer baseline best-correct visual acuity (BCVA, OR = 2.098, P<0.001), having severe myopic maculopathy (overall: P<0.001), prior myopic MNV in the fellow eye (OR = 4.105, P<0.001), presence of patchy atrophy (overall P<0.001), lacquer cracks (OR = 1.718, P<0.001), prior foveal retinal detachment (RD, OR = 3.269, P<0.001), prior macular hole (MH, OR = 0.641, P <0.001), prior macular retinoschisis (OR = 1.533, P<0.001), and prior macular edema (OR = 1.508, P<0.001) were significantly correlated with the development of myopic MNV. Eyes with MNV and patchy atrophy would require an intensive follow-up examination for myopic patients as the fellow eye would have a risk of >70% for the development of myopic MNV in 3-years and nearly 80% in 5-years. CONCLUSIONS: Clinicians need to pay special attention to eyes with severe grades of myopic maculopathy, prior myopic MNV in the fellow eye, presence of patchy atrophy, and prior foveal retinal detachment to determine the onset of myopic MNV.

CLINICAL AND MORPHOLOGIC FEATURES OF POSTERIOR STAPHYLOMA EDGES BY ULTRA-WIDEFIELD IMAGING IN PATHOLOGIC MYOPIA.

PURPOSE: To investigate morphologic features along posterior staphyloma edges in eyes with pathologic myopia using ultra-widefield optical coherence tomography imaging. METHODS: Highly myopic patients (refractive error < -8 diopters or axial length ≥26.5 mm) were consecutively examined by prototype ultra-widefield optical coherence tomography with a scan width of 23 mm and depth of 5 mm. Staphyloma edges were assessed for scleral, choroidal, and retinal status, as well as measurements of angle size. Findings were correlated with pigmentary changes observed on Optos fundus photography, and multivariate logistic regression analyses were performed. RESULTS: In 164 eyes diagnosed with posterior staphyloma by ultra-widefield optical coherence tomography, choroidal thinning and scleral protrusion were hallmark features of staphyloma edges, observed simultaneously in more than 95% of staphylomatous eyes. Outer neural retinal thinning was observed in 80 eyes (48.8%), whereas 15 eyes (9.1%) showed retinal pigment epithelium damage. The mean angle at the staphyloma edge was 23° ± 12.4° (range 8° to 77°). Larger angles were significant predictors of retinal thinning (adjusted odds ratio: 1.17, confidence interval: 1.09-1.25), and the staphyloma was detected by Optos pseudocolor fundus photography (adjusted odds ratio: 1.08, confidence interval: 1.02-1.15). CONCLUSION: These morphologic findings may provide a basis for exploring the natural evolution of posterior staphyloma as part of the development of pathologic myopia.

ROLE OF DILATED SUBFOVEAL CHOROIDAL VEINS IN EYES WITH MYOPIC MACULAR NEOVASCULARIZATION.

PURPOSE: To investigate the dilated choroidal veins (DCVs) at or around myopic macular neovascularizations (MNVs) and to determine whether there is a hemodynamic relationship between them. METHODS: Fifty-eight eyes of 57 patients with myopic MNVs were examined. Dilated choroidal veins were defined as choroidal veins whose diameter was 2X larger than adjacent veins. Indocyanine green angiography and swept-source optical coherence tomography images were reviewed to detect DCVs that crossed the subfoveal area. The filling sequence of the DCVs and MNVs was determined. RESULTS: Patients' mean age was 71.4 ± 10.6 years. The mean axial length was 29.3 ± 1.8 mm. Dilated choroidal veins below or around the MNV were found in 17 eyes (29.3%). Emissaries of the short posterior ciliary arteries were seen at or around MNVs in 8 of the 17 eyes. In these eyes, the short posterior ciliary artery was filled first or almost simultaneously with the filling of the MNV, followed by a laminar filling of the DCVs. In one eye, afferent arterioles from the short posterior ciliary arteries and efferent venules connected to DCVs were seen. CONCLUSION: Dilated choroidal veins are present below or around MNVs in about 30% of eyes with myopic MNVs. Our findings suggest that an MNV might be a vascular unit consisting of short posterior ciliary arteries, afferent arterioles, efferent venules, and DCVs.

Genome-Wide Mapping of Oxidative DNA Damage via Engineering of 8-Oxoguanine DNA Glycosylase.

The occurrence of 8-oxo-7,8-dihydroguanine (OG) in the genome, as one of the major DNA oxidative damages, has been implicated in an array of biological processes, ranging from mutagenesis to transcriptional regulation. Genome-wide mapping of oxidative damages could shed light on the underlying cellular mechanism. In the present study, we engineered the hOGG1 enzyme, a primary 8-oxoguanine DNA glycosylase, into a guanine oxidation-profiling tool. Our method, called enTRAP-seq, successfully identified more than 1400 guanine oxidation sites in the mouse embryonic fibroblast genome. These OG peaks were enriched in open chromatin regions and regulatory elements, including promoters, 5' untranslated regions, and CpG islands. Collectively, we present a simple and generalizable approach for the genome-wide profiling of DNA damages with high sensitivity and specificity.

CLINICAL FEATURES OF PATCHY CHORIORETINAL ATROPHY IN PATHOLOGIC MYOPIA.

PURPOSE: To reveal clinical features of patchy atrophy in pathologic myopia and investigate the status of the Bruch membrane and retinal pigment epithelium by swept-source optical coherence tomography. METHODS: This study reviewed highly myopic patients who visited the high myopia clinic between January 2015 and February 2018. Wide-field photographs and wide-field fundus autofluorescence fundus images were used as the primary method for identifying PAs, and swept-source optical coherence tomography images were used for investigating the retinochoroid status of PAs. RESULTS: Four hundred fifty-six PAs were detected in 137 eyes (118 patients). Patchy atrophys were located most often in the macular area (28.3%), followed by the inferior (25.9%), temporal (18.9%), nasal (14.5%), and superior (12.5%) region. All 210, PAs which had been fully or partially scanned by swept-source optical coherence tomography, showed a retinal pigment epithelium defect, and 174 (82.9%) PAs showed a Bruch membrane defect on the available scans. In 101 (82.8%) of 122 PAs with clearly detectable borders of the retinal pigment epithelium and Bruch membrane defect, the Bruch membrane defects were smaller than the retinal pigment epithelium defects. A dome-shape inward bulging of the sclera was observed in 10 PAs. CONCLUSION: These morphological findings may provide a basis for exploring the biomechanical etiology of the PAs as part of the development of pathologic myopia.

DEVELOPMENT OF MACULAR ATROPHY AFTER PARS PLANA VITRECTOMY FOR MYOPIC TRACTION MACULOPATHY AND MACULAR HOLE RETINAL DETACHMENT IN PATHOLOGIC MYOPIA.

PURPOSE: To determine the incidence and long-term outcome of macular atrophy (MA) after pars plana vitrectomy (PPV) in pathologic myopia. METHODS: Highly myopic patients who underwent PPV for myopic traction maculopathy and macular hole retinal detachment at Tokyo Medical and Dental University between 2012 and 2016 were studied. Fundus photographs and/or optical coherence tomography were examined before and after PPV at every visit. RESULTS: A total of 133 eyes were followed for 39 months with the mean age of 62.8 years and the mean axial length of 30.0 mm. Postoperatively, 14 eyes (10.5%) developed fovea-centered MA, observed initially as a small, isolated, whitish lesion at the center of fovea at 3.5 months after PPV. The appearance of the MA was distinctly different from the choroidal neovascularization-related MA or patchy atrophy-related MA. With time, the lesions enlarged circumferentially. In these 14 eyes, the final best-corrected visual acuity was worse than the baseline, although the difference was not significant. The occurrence of MA was significantly associated with the preoperative foveal status. CONCLUSION: The development of MA can occur in 11% of highly myopic eyes after PPV for myopic traction maculopathy and macular hole retinal detachment. This postoperative MA might be a new complication of pathologic myopia.