Ingestion and surgical retrieval of an endodontic file: a case report.

Ingestions and aspirations of foreign bodies are rare, but do occasionally occur during dental treatment. Although reports exist, few include photos demonstrating the extensive surgical intervention that may be necessary to manage such events. Perhaps this lack of visualization, and associated lack of awareness, is one of the reasons some clinicians still provide non-surgical root canal therapy (NSRCT) without a rubber dam. This case report outlines the medical treatment of a 30-year-old male who initially presented to a general dentist's office (not associated with the authors) for NSRCT of their mandibular right first molar. A rubber dam was not used for this procedure, during which the accidental ingestion of an endodontic K-file occurred. The patient was subsequently hospitalized for evaluation and treatment, consisting of numerous imaging studies, endoscopic evaluation, and surgical removal of the file from his small intestine. The ingestion of foreign bodies, and the associated complications, can be reduced through the routine use of a rubber dam, which is considered the standard of care for NSRCT. This case graphically illustrates the potential consequences associated with deviating from the standard of care and should remind clinicians that a rubber dam is necessary for all cases of NSRCT.

Incidental Findings in Small Field of View Cone-beam Computed Tomography Scans, Part 2: Interpretation with Aid of a Checklist.

INTRODUCTION: Cone-beam computed tomography (CBCT) scans are routinely used by endodontic residents and faculty at Tufts University School of Dental Medicine for diagnostic purposes but are not routinely read for pathologic findings by a radiologist. In a 2017 study by Oser et al (part 1), endodontic residents and a radiologist interpreted CBCT scans taken for endodontic diagnostic purposes, and their findings were compared. The results demonstrated that a radiologist is significantly more likely to report incidental findings in small field of view (FOV) scans. A limitation of this study was that the radiologist used a checklist of common findings to review the scans. The purpose of this study was to examine whether the use of a checklist would improve the sensitivity of the endodontic residents' reporting of incidental findings in small FOV CBCT scans. METHODS: The 203 small FOV CBCT scans used in part 1 were obtained and reviewed by endodontic residents in a systematic fashion. Radiographic findings were reported using a blank checklist. The results were compared with those previously reported. RESULTS: The radiologist reported abnormalities in 176 of the 203 subjects (87%), and the residents reported abnormalities in 184 of the 203 subjects (91%). There was an increase in false positive findings when the residents were using a checklist. CONCLUSIONS: The use of a checklist improved the sensitivity but decreased the specificity of the reporting of incidental findings in small FOV CBCT scans by endodontic residents.

Pre-Eruptive Intracoronal Resorption (PEIR): A Case Report.

Pre-Eruptive Intracoronal Resorption (PEIR) is a rare yet significant phenomenon in which an abnormal, well-circumscribed, radiolucent area develops in the tooth prior to eruption. This case report outlines the treatment of a 12 year old Hispanic female who was referred for endodontic evaluation of tooth #31 and subsequently diagnosed with PEIR. The patient's chief complaint was recorded as "spontaneous pain" in the lower right quadrant of her jaw. Clinical examination revealed a partially erupted tooth #31 with no visible decay. Radiographic examination, including a cone beam computed tomography scan, led to the detection of a radiolucent area surrounding the pulp chamber on the mesial aspect of tooth #31. Radiographically, the enamel appeared intact with no signs of perforation. Based on the clinical and radiographic evaluation, tooth #31 was determined to have PEIR, with the pulpal and periapical diagnosis of "Symptomatic Irreversible Pulpitis" and "Normal Apical Tissue," respectively. The Orthodontic consultation obtained for this patient recommended that tooth #31 be maintained at least until tooth #32 appeared in the oral cavity and could be used as a replacement. Therefore, a treatment plan involving vital pulp therapy and gingivectomy was selected. During the procedure, granulation tissue was excavated and sent for histological evaluation, which concluded the presence of "granulation tissue with acute and chronic inflammation". No caries were detected. Following the procedure, the tooth was found to be asymptomatic with continued root development. A positive response to Electric Pulp Test was achieved after 3.5 years of follow up.

Thrombospondin 1 missense alleles induce extracellular matrix protein aggregation and TM dysfunction in congenital glaucoma.

Glaucoma is a highly heritable disease that is a leading cause of blindness worldwide. Here, we identified heterozygous thrombospondin 1 (THBS1) missense alleles altering p.Arg1034, a highly evolutionarily conserved amino acid, in 3 unrelated and ethnically diverse families affected by congenital glaucoma, a severe form of glaucoma affecting children. Thbs1R1034C-mutant mice had elevated intraocular pressure (IOP), reduced ocular fluid outflow, and retinal ganglion cell loss. Histology revealed an abundant, abnormal extracellular accumulation of THBS1 with abnormal morphology of juxtacanalicular trabecular meshwork (TM), an ocular tissue critical for aqueous fluid outflow. Functional characterization showed that the THBS1 missense alleles found in affected individuals destabilized the THBS1 C-terminus, causing protein misfolding and extracellular aggregation. Analysis using a range of amino acid substitutions at position R1034 showed that the extent of aggregation was correlated with the change in protein-folding free energy caused by variations in amino acid structure. Extracellular matrix (ECM) proteins, especially fibronectin, which bind to THBS1, also accumulated within THBS1 deposits. These results show that missense variants altering THBS1 p.Arg1034 can cause elevated IOP through a mechanism involving impaired TM fluid outflow in association with accumulation of aggregated THBS1 in the ECM of juxtacanalicular meshwork with altered morphology.

Anti-angiogenic properties of microRNA-29a in preclinical ocular models.

Abnormal neovascularization is an important cause of blindness in many ocular diseases, for which the etiology and pathogenic mechanisms remain incompletely understood. Recent studies have revealed the diverse roles of noncoding RNAs in various biological processes and facilitated the research and development of the clinical application of numerous RNA drugs, including microRNAs. Here, we report the antiangiogenic activity of microRNA-29a (miR-29a) in three animal models of ocular neovascularization. The miR-29a knockout (KO) mice displayed enhanced vessel pruning, resulting in a decreased vascularized area during retinal development. In contrast, miR-29a deletion in adult mice accelerated angiogenesis in preclinical disease models, including corneal neovascularization, oxygen-induced retinopathy, and choroidal neovascularization, while the administration of agomir-29a ameliorated pathological neovascularization. Furthermore, miR-29a exerted inhibitory effects on endothelial cell proliferation, migration, and tube formation capacities. RNA sequencing analysis of retinas from miR-29a KO mice and RNA interference experiments identified platelet-derived growth factor C and several extracellular matrix genes as downstream targets of miR-29a involved in regulating ocular angiogenesis. Our data suggest that miR-29a may be a promising clinical candidate for the treatment of neovascular diseases.

The Prominin-1-Derived Peptide Improves Cardiac Function Following Ischemia.

Myocardial infarction (MI) remains the leading cause of death in the western world. Despite advancements in interventional revascularization technologies, many patients are not candidates for them due to comorbidities or lack of local resources. Non-invasive approaches to accelerate revascularization within ischemic tissues through angiogenesis by providing Vascular Endothelial Growth Factor (VEGF) in protein or gene form has been effective in animal models but not in humans likely due to its short half-life and systemic toxicity. Here, we tested the hypothesis that PR1P, a small VEGF binding peptide that we developed, which stabilizes and upregulates endogenous VEGF, could be used to improve outcome from MI in rodents. To test this hypothesis, we induced MI in mice and rats via left coronary artery ligation and then treated animals with every other day intraperitoneal PR1P or scrambled peptide for 14 days. Hemodynamic monitoring and echocardiography in mice and echocardiography in rats at 14 days showed PR1P significantly improved multiple functional markers of heart function, including stroke volume and cardiac output. Furthermore, molecular biology and histological analyses of tissue samples showed that systemic PR1P targeted, stabilized and upregulated endogenous VEGF within ischemic myocardium. We conclude that PR1P is a potential non-invasive candidate therapeutic for MI.

Identification of Basp1 as a novel angiogenesis-regulating gene by multi-model system studies.

We have previously used the genetic diversity available in common inbred mouse strains to identify quantitative trait loci (QTLs) responsible for the differences in angiogenic response using the corneal micropocket neovascularization (CoNV) assay. Employing a mouse genome-wide association study (GWAS) approach, the region on chromosome 15 containing Basp1 was identified as being significantly associated with angiogenesis in inbred strains. Here, we developed a unique strategy to determine and verify the role of BASP1 in angiogenic pathways. Basp1 expression in cornea had a strong correlation with a haplotype shared by mouse strains with varied angiogenic phenotypes. In addition, inhibition of BASP1 demonstrated a dosage-dependent effect in both primary mouse brain endothelial and human microvascular endothelial cell (HMVEC) migration. To investigate its role in vivo, we knocked out basp1 in transgenic kdrl:zsGreen zebrafish embryos using a widely adopted CRISPR-Cas9 system. These embryos had severely disrupted vessel formation compared to control siblings. We further show that basp1 promotes angiogenesis by upregulating ß-catenin gene and the Dll4/Notch1 signaling pathway. These results, to the best of our knowledge, provide the first in vivo evidence to indicate the role of Basp1 as an angiogenesis-regulating gene and opens the potential therapeutic avenues for a wide variety of systemic angiogenesis-dependent diseases.

Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England.

The SARS-CoV-2 lineage B.1.1.7, designated variant of concern (VOC) 202012/01 by Public Health England1, was first identified in the UK in late summer to early autumn 20202. Whole-genome SARS-CoV-2 sequence data collected from community-based diagnostic testing for COVID-19 show an extremely rapid expansion of the B.1.1.7 lineage during autumn 2020, suggesting that it has a selective advantage. Here we show that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by S gene target failures (SGTF) in community-based diagnostic PCR testing. Analysis of trends in SGTF and non-SGTF case numbers in local areas across England shows that B.1.1.7 has higher transmissibility than non-VOC lineages, even if it has a different latent period or generation time. The SGTF data indicate a transient shift in the age composition of reported cases, with cases of B.1.1.7 including a larger share of under 20-year-olds than non-VOC cases. We estimated time-varying reproduction numbers for B.1.1.7 and co-circulating lineages using SGTF and genomic data. The best-supported models did not indicate a substantial difference in VOC transmissibility among different age groups, but all analyses agreed that B.1.1.7 has a substantial transmission advantage over other lineages, with a 50% to 100% higher reproduction number.

Clinical Response to COVID-19 and Utilization of an Emergency Dental Clinic in an Academic Institution.

INTRODUCTION: The spread of coronavirus disease 2019 (COVID-19) in the spring of 2020 resulted in the temporary suspension of elective dental procedures and clinical dental education in academic institutions. This study describes the use of the Tufts University School of Dental Medicine emergency dental clinic during the peak surge in COVID-19 cases in Massachusetts, highlighting the number of endodontic emergencies. METHODS: Aggregate data from clinical encounters and call records to an emergency triage phone line from March 30 through May 8, 2020, were used to describe the characteristics of dental emergencies, clinical encounters, and procedures performed. RESULTS: A total of 466 patient interactions occurred during this period, resulting in 199 patients advised by phone and 267 clinical encounters. The most common dental emergencies were severe dental pain from pulpal inflammation (27.7% of clinical encounters) followed by a surgical postoperative visit (13.1%). The most frequent procedures were extractions (13.9% of clinical encounters) and surgical follow-up (13.5%); 50.2% of the clinical encounters were categorized as aerosol generating, and 86.1% of encounters would have required treatment in a hospital emergency department if dental care was not available. There were no known transmissions of severe acute respiratory syndrome coronavirus-2 among clinic providers, patients, or staff during this period. CONCLUSIONS: These results highlight the importance of endodontic diagnosis and treatment in the provision of emergency dental care during a pandemic and demonstrate that dental treatment can be provided in a manner that minimizes the risk of viral transmission, maintaining continuity of care for a large patient population.

Angiogenic responses in a 3D micro-engineered environment of primary endothelial cells and pericytes.

Angiogenesis plays a key role in the pathology of diseases such as cancer, diabetic retinopathy, and age-related macular degeneration. Understanding the driving forces of endothelial cell migration and organization, as well as the time frame of these processes, can elucidate mechanisms of action of important pathological pathways. Herein, we have developed an organ-specific microfluidic platform recapitulating the in vivo angiogenic microenvironment by co-culturing mouse primary brain endothelial cells with brain pericytes in a three-dimensional (3D) collagen scaffold. As a proof of concept, we show that this model can be used for studying the angiogenic process and further comparing the angiogenic properties between two different common inbred mouse strains, C57BL/6J and 129S1/SvlmJ. We further show that the newly discovered angiogenesis-regulating gene Padi2 promotes angiogenesis through Dll4/Notch1 signaling by an on-chip mechanistic study. Analysis of the interplay between primary endothelial cells and pericytes in a 3D microfluidic environment assists in the elucidation of the angiogenic response.

The Association between Choice of Diagnostic Imaging Modality and Long-term Treatment Outcomes for Patients Undergoing Nonsurgical Root Canal Treatment on Maxillary First Molars.

INTRODUCTION: Radiography has played a fundamental role in the advancement of nonsurgical root canal therapy (NSRCT), allowing for more accurate diagnosis and treatment. Typically, providers choose to perform NSRCT using periapical (PA) radiographs alone or, often in more difficult cases, in conjunction with cone-beam computed tomographic (CBCT) imaging. This study aimed to evaluate the outcomes of NSRCT based on imaging modality selection for the initial treatment of maxillary first molars. METHODS: A retrospective chart review was conducted using 1385 cases of NSRCT on maxillary first molars. Charts were reviewed for patient demographics and treatment outcomes. Based on the imaging modality used, patients were stratified into 2 groups (PA radiographs alone or PA radiographs + CBCT imaging). Those who required additional treatment(s) after the completion of NSRCT were classified as having "posttreatment disease." Statistical analysis was performed to assess the differences between groups. RESULTS: After the completion of primary endodontic therapy, 5.8% (n = 81) of the entire sample had posttreatment disease. CBCT imaging was used in 13.4% (n = 185) of NSRCTs. Although not significant, cases that were difficult enough to require the use of CBCT imaging had a higher rate of posttreatment disease compared to those that could be completed with PA radiographs alone (8.6% vs 5.4%, P > .05). Results from a multivariable logistic regression model showed that the need for CBCT imaging had a nonsignificant positive association with posttreatment disease (P > .05). CONCLUSIONS: The decision to use CBCT imaging appears to serve as a proxy for case complexity and the associated increase in risk of posttreatment disease. This is important to keep in mind when assessing treatment prognosis.

Low dose amiodarone reduces tumor growth and angiogenesis.

Amiodarone is an anti-arrhythmic drug that was approved by the US Food and Drug Administration (FDA) in 1985. Pre-clinical studies suggest that Amiodarone induces cytotoxicity in several types of cancer cells, thus making it a potential candidate for use as an anti-cancer treatment. However, it is also known to cause a variety of severe side effects. We hypothesized that in addition to the cytotoxic effects observed in cancer cells Amiodarone also has an indirect effect on angiogensis, a key factor in the tumor microenvironment. In this study, we examined Amiodarone's effects on a murine tumor model comprised of U-87 MG glioblastoma multiforme (GBM) cells, known to form highly vascularized tumors. We performed several in vitro assays using tumor and endothelial cells, along with in vivo assays utilizing three murine models. Low dose Amiodarone markedly reduced the size of GBM xenograft tumors and displayed a strong anti-angiogenic effect, suggesting dual cancer fighting properties. Our findings lay the ground for further research of Amiodarone as a possible clinical agent that, used in safe doses, maintains its dual properties while averting the drug's harmful side effects.

A Method for Developing Novel 3D Cornea-on-a-Chip Using Primary Murine Corneal Epithelial and Endothelial Cells.

Microfluidic-based organ-on-a-chip assays with simultaneous coculture of multi-cell types have been widely utilized for basic research and drug development. Here we describe a novel method for a primary cell-based corneal microphysiological system which aims to recapitulate the basic functions of the in vivo cornea and to study topically applied ocular drug permeation. In this study, the protocols for isolating and cultivating primary corneal epithelial cells and endothelial cells from mouse inbred strain C57BL/6J were optimized, to allow for the development of a primary-cell based microfluidic 3D micro-engineered cornea. This tissue unit, by overcoming the limitations of 2D conventional cell culture, supports new investigations on cornea function and facilitates drug delivery testing.

MicroRNA-18a-5p Administration Suppresses Retinal Neovascularization by Targeting FGF1 and HIF1A.

Pathologic ocular neovascularization commonly results in visual impairment or even blindness in numerous fundus diseases, including proliferative diabetic retinopathy (PDR), retinopathy of prematurity (ROP), and age-related macular degeneration (AMD). MicroRNAs regulate angiogenesis through modulating target genes and disease progression, making them a new class of targets for drug discovery. In this study, we investigated the potential role of miR-18a-5p in retinal neovascularization using a mouse model of oxygen-induced proliferative retinopathy (OIR). We found that miR-18a-5p was highly expressed in the retina of pups as well as retinal endothelial cells, and was consistently down-regulated during retinal development. On the other hand, miR-18a-5p was increased significantly during pathologic neovascularization in the retinas of OIR mice. Moreover, intravitreal administration of miRNA mimic, agomiR-18a-5p, significantly suppressed retinal neovascularization in OIR models. Accordingly, agomir-18a-5p markedly suppressed human retinal microvascular endothelial cell (HRMEC) function including proliferation, migration, and tube formation ability. Additionally, we demonstrated that miR-18a-5p directly down-regulated known vascular growth factors, fibroblast growth factor 1 (FGF1) and hypoxia-inducible factor 1-alpha (HIF1A), as the target genes. In conclusion, miR-18a-5p may be a useful drug target for pathologic ocular neovascularization.

Validation and Clinical Applications of a Comprehensive Next Generation Sequencing System for Molecular Characterization of Solid Cancer Tissues.

Identification of somatic molecular alterations in primary and metastatic solid tumor specimens can provide critical information regarding tumor biology and its heterogeneity, and enables the detection of molecular markers for clinical personalized treatment assignment. However, the optimal methods and target genes for clinical use are still being in development. Toward this end, we validated a targeted amplification-based NGS panel (Oncomine comprehensive assay v1) on a personal genome machine sequencer for molecular profiling of solid tumors. This panel covers 143 genes, and requires low amounts of DNA (20 ng) and RNA (10 ng). We used 27 FFPE tissue specimens, 10 cell lines, and 24 commercial reference materials to evaluate the performance characteristics of this assay. We also evaluated the performance of the assay on 26 OCT-embedded fresh frozen specimens (OEFF). The assay was found to be highly specific (>99%) and sensitive (>99%), with low false-positive and false-negative rates for single-nucleotide variants, indels, copy number alterations, and gene fusions. Our results indicate that this is a reliable method to determine molecular alterations in both fixed and fresh frozen solid tumor samples, including core needle biopsies.

Jumpstart Mirror Trainer: A New Device for Teaching Mirror Skills to First-Year Dental Students.

Learning indirect vision with a dental mirror is challenging and can be overwhelming for beginning dental students. The Jumpstart Mirror Trainer is a new device that allows students to become proficient with mirror use before the start of preclinic without requiring in-class practice sessions. The aim of this study, conducted in 2017, was to compare the effectiveness of the Jumpstart Mirror Trainer with the Mirroprep for teaching indirect motor skills. Forty-seven first-year dental students were randomized into three groups to use the Jumpstart Mirror Trainer, Mirroprep, or a control device for 15 minutes a day for ten days. To assess indirect motor skills improvement, students performed a maxillary cavity preparation before and after using their devices. A survey was used to assess students' comfort level with mirror skills and perceived helpfulness of the exercises. Forty students completed the study. The Jumpstart Mirror Trainer activities improved the students' scores significantly more than the Mirroprep activities (p=0.04) and the control device (p=0.006). Students in the Jumpstart Mirror Trainer group rated their device as being significantly more helpful than the control group rated its device in preparing them for the evaluation (p=0.001). There was no statistically significant difference in perceived helpfulness between the Mirroprep group and the control group (p=0.75). These results suggest that the Jumpstart Mirror Trainer may be able to improve students' indirect motor skills without requiring in-class practice sessions and to do so more effectively than other existing methods.

PR1P ameliorates neurodegeneration through activation of VEGF signaling pathway and remodeling of the extracellular environment.

Neurodegenerative diseases affect millions of people worldwide. Optic neuropathies are the most commonly occurring neurodegenerative diseases, characterized by progressive retinal ganglion cell (RGC) degeneration. We recently reported that Prominin-1, a protein found on the surface of stem cells, interacts with VEGF and enhances its activity. VEGF is known to have various protective roles in the nervous system. Subsequently, we have developed a 12-mer peptide derived from Prominin-1, named PR1P, and investigated its effects on neuronal survival of damaged RGCs in a rat model of optic nerve crush (ONC). PR1P prevented RGC apoptosis resulting in improvement of retinal function in the rat ONC model. PR1P treatment significantly increased phosphorylation of ERK and AKT and expression its downstream proteins c-fos and Egr-1 in the retina. Additionally, PR1P beneficially increased the MMP-9/TIMP-1 ratio and promoted glial activation in the retina of ONC rats. Thus, PR1P displayed neuroprotective effects through enhanced VEGF-driven neuronal survival and reconstruction of the extracellular environment in ONC model. Our data indicate that PR1P may be a promising new clinical candidate for the treatment of neurodegenerative diseases.

Can bone scans guide therapy with radium-223 dichloride for prostate cancer bone metastases?

BACKGROUND: Radium-223 dichloride (Ra-223 Xofigo) has recently been approved as an addition to the host of available therapies in the USA as a treatment option for metastatic castrate-resistant prostate cancer (mCRPC) with bone metastases. This study describes our initial experience in patients treated with Ra-223 dichloride. It attempts to optimize patients' selection for the best outcome from Ra-223 dichloride therapy. METHODS: Consecutive patients who were referred for treatment with Ra-223 dichloride were prospectively followed. Patients' demographics, functional status per the Eastern Cooperative Oncology Group (ECOG) performance score, pain level per the numeric rating score (NRS), prostate-specific antigen (PSA), creatinine, and hematological values were compared at baseline and at the end of therapy. Patients also had a bone scan before starting therapy and at the end of therapy. Patients were divided into the favorable response (FR) group if their pain and/or functional status improved and the unfavorable response (UR) group if they did not improve, deteriorated, or deceased. Bone scan findings before and after Ra-223 dichloride therapy were compared in both the FR and UR groups. RESULTS: Twenty patients were treated with Ra-223 dichloride. Twelve patients had innumerable bone metastases, three patients had super scans, and three patients had two to seven bone lesions. Two patients were lost to follow-up after the first injection. There were eight patients in the FR group and 10 patients in the UR group. Patients with UR had mean ECOG and NRS pain scores of 1.3 and 5.0 versus 0.8 and 4.4 in the FR group. The mean PSA and creatinine levels in the UR group were 445.2 ng/mL and 1.2 mg/dL versus 22.7 ng/mL and 1.1 mg/dL in the FR group. The mean hemoglobin, platelets, and absolute neutrophil values were 11.2 g/dL, 314.9 K/cmm, and 7.3 K/cmm in the UR group versus 11.6 g/dL, 207.0 K/cmm, and 6.2 K/cmm in the FR group. Seven of the eight patients with FR had a bone scan at the end of therapy showing improvement in five patients, a mixed response in one patient, and progression in another patient. Five patients in the UR group completed five or six injections and had bone scans showing flare of bone metastases in three patients, progression in one patient, and improvement in the fifth patient. Three patients in the UR group died after the first or second injections. Two of these patients had baseline super scans and the third one had widespread bone metastases. CONCLUSION: mCRPC patients with lower PSA levels at baseline and fewer bone lesions are more likely to respond favorably to Ra-223 dichloride therapy.

Epsin deficiency promotes lymphangiogenesis through regulation of VEGFR3 degradation in diabetes.

Impaired lymphangiogenesis is a complication of chronic complex diseases, including diabetes. VEGF-C/VEGFR3 signaling promotes lymphangiogenesis, but how this pathway is affected in diabetes remains poorly understood. We previously demonstrated that loss of epsins 1 and 2 in lymphatic endothelial cells (LECs) prevented VEGF-C-induced VEGFR3 from endocytosis and degradation. Here, we report that diabetes attenuated VEGF-C-induced lymphangiogenesis in corneal micropocket and Matrigel plug assays in WT mice but not in mice with inducible lymphatic-specific deficiency of epsins 1 and 2 (LEC-iDKO). Consistently, LECs isolated from diabetic LEC-iDKO mice elevated in vitro proliferation, migration, and tube formation in response to VEGF-C over diabetic WT mice. Mechanistically, ROS produced in diabetes induced c-Src-dependent but VEGF-C-independent VEGFR3 phosphorylation, and upregulated epsins through the activation of transcription factor AP-1. Augmented epsins bound to and promoted degradation of newly synthesized VEGFR3 in the Golgi, resulting in reduced availability of VEGFR3 at the cell surface. Preclinically, the loss of lymphatic-specific epsins alleviated insufficient lymphangiogenesis and accelerated the resolution of tail edema in diabetic mice. Collectively, our studies indicate that inhibiting expression of epsins in diabetes protects VEGFR3 against degradation and ameliorates diabetes-triggered inhibition of lymphangiogenesis, thereby providing a novel potential therapeutic strategy to treat diabetic complications.