Atg16L1 as a Novel Biomarker and Autophagy Gene for Diabetic Retinopathy.

Objective: Accumulating evidence suggests the critical role of autophagy in the pathogenesis of diabetic retinopathy (DR). In the current study, we aim to identify autophagy genes involved in DR via microarray analyses. Methods: Gene microarrays were performed to identify differentially expressed lncRNAs/mRNAs between normal and DR retinas. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of lncRNA-coexpressed mRNAs were used to determine the related pathological pathways and biological modules. Real-time polymerase chain reactions (PCR) were conducted to validate the microarray analyses. Results: A total of 2474 significantly dysregulated lncRNAs and 959 differentially expressed mRNAs were identified in the retina of DR. Based upon Signalnet analysis, Bcl2, Gabarapl2, Atg4c, and Atg16L1 participated the process of cell death in DR. Moreover, real-time PCR revealed significant upregulation of Atg16L1. Conclusion: This study indicated the importance and potential role of Atg16L1, one of the autophagy genes, as a biomarker in DR development and progression

Adiponectin-Mediated Promotion of CD44 Suppresses Diabetic Vascular Inflammatory Effects

While adiponectin (APN) was known to significantly abolish the diabetic endothelial inflammatory response, the specific mechanisms have yet to be elucidated. Aortic vascular tissues from mice fed normal and high-fat diets (HFD) were analyzed by transcriptome analysis. GO functional annotation showed that APN inhibited vascular endothelial inflammation in an APPL1-dependent manner. We confirmed that activation of the Wnt/β-catenin signaling plays a key role in APN-mediated anti-inflammation. Mechanistically, APN promoted APPL1/reptin complex formation and β-catenin nuclear translocation. Simultaneously, we identified APN promoted the expression of CD44 by activating TCF/LEF in an APPL1-mediated manner. Clinically, the serum levels of APN and CD44 were decreased in diabetes; the levels of these two proteins were positively correlated. Functionally, treatment with CD44 C-terminal polypeptides protected diabetes-induced vascular endothelial inflammation in vivo. Collectively, we provided a roadmap for APN-inhibited vascular inflammatory effects and CD44 might represent potential targets against the diabetic endothelial inflammatory effect

Scleral Buckling for Primary Retinal Detachment: Outcomes of Scleral Tunnels versus Scleral Sutures

Purpose: There are primarily two techniques for affixing the scleral buckle (SB) to the sclera in the repair of rhegmatogenous retinal detachment (RRD): scleral tunnels or scleral sutures. Methods: This retrospective study examined all patients with primary RRD who were treated with primary SB or SB combined with vitrectomy from January 1, 2015 through December 31, 2015 across six sites. Two cohorts were examined: SB affixed using scleral sutures versus scleral tunnels. Pre- and postoperative variables were evaluated including visual acuity, anatomic success, and postoperative strabismus. Results: The mean preoperative logMAR VA for the belt loop cohort was 1.05 ± 1.06 (Snellen 20/224) and for the scleral suture cohort was 1.03 ± 1.04 (Snellen 20/214, p = 0.846). The respective mean postoperative logMAR VAs were 0.45 ± 0.55 (Snellen 20/56) and 0.46 ± 0.59 (Snellen 20/58, p = 0.574). The single surgery success rate for the tunnel cohort was 87.3% versus 88.6% for the suture cohort (p = 0.601). Three patients (1.0%) in the scleral tunnel cohort developed postoperative strabismus, but only one patient (0.1%) in the suture cohort (p = 0.04, multivariate p = 0.76). All cases of strabismus occurred in eyes that underwent SB combined with PPV (p = 0.02). There were no differences in vision, anatomic success, or strabismus between scleral tunnels versus scleral sutures in eyes that underwent primary SB. Conclusion: Scleral tunnels and scleral sutures had similar postoperative outcomes. Combined PPV/SB in eyes with scleral tunnels might be a risk for strabismus post retinal detachment surgery

HCTNet: A Hybrid ConvNet-Transformer Network for Retinal Optical Coherence Tomography Image Classification

Automatic and accurate optical coherence tomography (OCT) image classification is of great significance to computer-assisted diagnosis of retinal disease. In this study, we propose a hybrid ConvNet-Transformer network (HCTNet) and verify the feasibility of a Transformer-based method for retinal OCT image classification. The HCTNet first utilizes a low-level feature extraction module based on the residual dense block to generate low-level features for facilitating the network training. Then, two parallel branches of the Transformer and the ConvNet are designed to exploit the global and local context of the OCT images. Finally, a feature fusion module based on an adaptive re-weighting mechanism is employed to combine the extracted global and local features for predicting the category of OCT images in the testing datasets. The HCTNet combines the advantage of the convolutional neural network in extracting local features and the advantage of the vision Transformer in establishing long-range dependencies. A verification on two public retinal OCT datasets shows that our HCTNet method achieves an overall accuracy of 91.56% and 86.18%, respectively, outperforming the pure ViT and several ConvNet-based classification methods

Corneal arcus and xanthomas in homozygous familial hypercholesterolemia: First report from China

We report the case of a 12-year-old male who developed corneal arcus and multiple skin lesions with a 10-year history of xanthomas. The lesions appeared over his fingers, hands, elbows, knees, buttocks and feet. Laboratory studies showed a total serum cholesterol level of 752.1 mg/dL; a triglyceride level of 96.6 mg/dL; a low-density lipoprotein cholesterol level of 661.3 mg/dL. Findings were consistent with homozygous familial hypercholesterolemia. To our knowledge, this is the first such case to be reported from China

Continuous High Frequency Deep Brain Stimulation of the Rat Anterior Insula Attenuates the Relapse Post Withdrawal and Strengthens the Extinction of Morphine Seeking

Deep brain stimulation (DBS) modulates the neuronal activity in specific brain circuits and has been recently considered as a promising intervention for refractory addiction. The insula cortex is the hub of interoception and is known to be involved in different aspects of substance use disorder. In the present study, we investigate the effects of continuous high frequency DBS in the anterior insula (AI) on drug-seeking behaviors and examined the molecular mechanisms of DBS action in morphine-addicted rats. Sprague-Dawley rats were trained to the morphine-conditioned place preference (CPP, day 1-8) followed by bilaterally implanted with DBS electrodes in the AI (Day 10) and recovery (Day 10-15). Continuous high-frequency (HF) -DBS (130 Hz, 150 mu A, 90 mu s) was applied during withdrawal (Day 16-30) or extinction sessions. CPP tests were conducted on days 16, 30, 40 during withdrawal session and several rats were used for proteomic analysis on day 30. Following the complete extinction, morphine-CPP was reinstated by a priming dose of morphine infusion (2 mg/kg). The open field and novel objective recognition tests were also performed to evaluate the DBS side effect on the locomotion and recognition memory. Continuous HF-DBS in the AI attenuated the expression of morphine-CPP post-withdrawal (Day 30), but morphine addictive behavior relapsed 10 days after the cessation of DBS (Day 40). Continuous HF-DBS reduced the period to full extinction of morphine-CPP and blocked morphine priming-induced recurrence of morphine addiction. HF-DBS in the AI had no obvious effect on the locomotor activity and novel objective recognition and did not cause anxiety-like behavior. In addition, our proteomic analysis identified eight morphine-regulated proteins in the AI and their expression levels were reversely changed by HF-DBS. Continuous HF-DBS in the bilateral anterior insula prevents the relapse of morphine place preference after withdrawal, facilitates its extinction, blocks the reinstatement induced by morphine priming and reverses the expression of morphine-regulated proteins. Our findings suggest that manipulation of insular activity by DBS could be a potential intervention to treat substance use disorder, although future research is warranted