Digital Commons Network^™

Optimized Legionella Expression Strain For Affinity Purification Of His-Tagged Membrane Proteins Eliminates Major Multimeric Contaminant, Sukhithasri Vijayrajratnam, Jonasz B Patkowski, Joshua Khorsandi, Wandy L Beatty, Shanmugapriya Kannaiah, Ahmet Hasanovic, Tamara J O'Connor, Tiago R D Costa, Joseph P Vogel

2020-Current year OA Pubs

Polyhistidine tags are frequently used for isolating proteins through

The Loss Of Opa1 Accelerates Intervertebral Disc Degeneration And Osteoarthritis In Aged Mice, Vedavathi Madhu, Miriam Hernandaz-Meadows, Ashley Coleman, Kimheak Sao, Kameron Inguito, Owen Haslam, Paige K Boneski, Hiromi Sesaki, Ruteja A Barve, John A Collins, Makarand V Risbud

2020-Current year OA Pubs

Recent studies have highlighted the importance of mitochondria in NP cells and articular chondrocyte health. Since the understanding of mechanisms governing mitochondrial dynamics in these tissues is lacking, we investigated the role of OPA1, a mitochondrial fusion protein, in their homeostasis. OPA1 knockdown in NP cells altered mitochondrial size and cristae shape and increased the oxygen consumption rate. OPA1 governed the morphology of multiple organelles, including peroxisomes, early endosomes and cis-Golgi and loss resulted in the dysregulation of autophagy. Metabolic profiling and

Exploitable Mechanisms Of Antibody And Car Mediated Macrophage Cytotoxicity, Tianyi Liu, Alexander B Kim, Young Ah Goo, Minsoo Son, Jaenyeon Kim, Carl J Deselm, Et Al.

2020-Current year OA Pubs

Macrophages infiltrate solid tumors and either support survival or induce cancer cell death through phagocytosis or cytotoxicity. To uncover regulators of macrophage cytotoxicity towards cancer cells, we perform two co-culture CRISPR screens using CAR-macrophages targeting different tumor associated antigens. Both identify ATG9A as an important regulator of this cytotoxic activity. In vitro and in vivo, ATG9A depletion in cancer cells sensitizes them to macrophage-mediated killing. Proteomic and lipidomic analyses reveal that ATG9A deficiency impairs the cancer cell response to macrophage-induced plasma membrane damage through defective lysosomal exocytosis, reduced ceramide production, and disrupted caveolar endocytosis. Depleting non-cytotoxic macrophages using CSF1R inhibition …

Participation In Activities Among People With Long-Term Spinal Cord Injury In Sweden And The Usa - An Explorative Study Using Secondary Data Analysis, Jessica L Dashner, Ulrica Antepohl

2020-Current year OA Pubs

STUDY DESIGN: Secondary data analysis.

OBJECTIVE: To explore differences in participation, secondary health complications, and the use of assistive devices and personal assistance among people with long-term SCI in Sweden and the USA.

SETTING: Community dwelling individuals with SCI in Sweden and USA.

METHODS: Secondary analysis of data collected via PARTS-Mv3 among individuals living with SCI in Sweden (n = 73) and in the USA (n = 45). Descriptive analyses provided information regarding the participants, their participation in activities, and secondary health complications, together with the use of assistive devices and personal assistance.

RESULTS: Both samples included more males than …

Incident Depression After Breast Cancer Among Older Asian, Native Hawaiian, And Pacific Islander Women, Alzina Koric, Chun-Pin Esther Chang, Yuan-Chin Amy Lee, Mei Wei, Catherine Lee, Jing Wang, Mia Hashibe

2020-Current year OA Pubs

BACKGROUND: Longitudinal studies examining mental health outcomes among older (≥66 years) Asian, Native Hawaiian, and Pacific Islander (ANHPI) women diagnosed with breast cancer are limited. We evaluated incident depression after breast cancer among specific groups of older ANHPI compared with older non-Hispanic White (NHW) women. Predictors of depression and the risk of death following early onset of depression after breast cancer were also evaluated.

METHODS: A cohort of 26 776 older ANHPI women in the United States diagnosed with breast cancer between 2000 and 2017 was identified from the SEER-Medicare linked claims. There were 6694 older ANHPI and 20 082 …

Sexually Dimorphic Impact Of Prenatal Hyperandrogenism On Offspring Growth Trajectory In Sheep, Eylem Topaktas, Joseph Ciarelli, Stephanie Domke, Brooke Pallas, Adel Ghnenis, Mansi Agarwal, Charles Goss, Kevin Cho, Leah P Shriver, Gary J Patti, Vasantha Padmanabhan, Arpita Kalla Vyas

2020-Current year OA Pubs

In a translationally relevant ovine model of gestational hyperandrogenism we have previously reported cardiometabolic disruption in female offspring (males were not extensively studied). We hypothesized that gestational hyperandrogenism would lead to sex-specific disruption in offspring's growth, cytokine and metabolic milieu, potential mediators of cardiometabolic disease (CMD). 100 mg Testosterone propionate (T) or vehicle (C) was administered intramuscularly twice weekly between gestational days (GD) 30-90. Two cohorts of offspring were generated, including both males and females. Fetal weight and systemic metabolomics were analyzed in the fetal cohort (GD120). Growth trajectory, systemic cytokines, and metabolomics were analyzed in the postnatal cohort. Data …

Soft Tissue Stabilization Of Midcarpal Instability In Ehlers-Danlos Patients Using A Cadaveric Tendon Graft, Mohammed Muneer, Fadi Bouri, Kjell Van Royen, Saif Badran, Jorge I. Quintero, Tuna Ozyurekoglu

2020-Current year OA Pubs

Ehlers-Danlos syndrome (EDS) is a group of hereditary disorders that affects collagen synthesis. In the wrist, pain and midcarpal laxity may affect up to 70% of EDS patients. The mainstay treatment of midcarpal instability in patients with ligamentous injury but not EDS includes orthotics, physiotherapy, and activity modification. These methods of conservative treatment may be unsuccessful in controlling instability in the longer term. Using autologous tendon for reconstructing midcarpal instability in patients with EDS carries the risk of loosening over time due to intrinsic abnormalities in collagen metabolism. In this article, we present a novel surgical technique using a cadaveric …

The Impact Of Diabetes And Metabolic Syndrome Burden On Pain, Neuropathy Severity And Fiber Type, Long Davalos, Brian C Callaghan, Lavanya Muthukumar, Simone Thomas, Evan L Reynolds, A Gordon Smith, J Robinson Singleton, Ahmet Höke, Senda Ajroud-Driss, Mazen M Dimachkie, Stefanie Geisler, David M Simpson, Pnrr Study Group, Amro M Stino

2020-Current year OA Pubs

OBJECTIVE: Determine the association between diabetes and metabolic syndrome (MetS) burden (number of MetS criteria fulfilled) and pain, neuropathy severity, and fiber type involvement in individuals with established polyneuropathy.

METHODS: The Peripheral Neuropathy Research Registry was queried for individuals with type 1 and type 2 diabetes (DPN) and non-diabetic peripheral neuropathy (cryptogenic sensory polyneuropathy and prediabetes) using cross-sectional observational data. Associations between diabetes or MetS burden and pain presence (yes/no), neuropathy severity (Total Neuropathy Score reduced), and fiber type involvement (pinprick, vibration, and proprioception examination-small, large, mixed) using logistic, linear, and multinomial regression models were determined.

RESULTS: A total of …

Medications To Reduce Breast Cancer Risk: A Network Meta-Analysis Of Randomized Controlled Trials, Ghazaleh Pourali, Minglu Liu, Supriya S Sherpa, Angela Hardi, Chongliang Luo, Adetunji T Toriola

2020-Current year OA Pubs

BACKGROUND: Given the rising incidence of breast cancer, especially in premenopausal women, there is an urgent need to identify additional risk-reducing medications to accelerate prevention, as only a few are currently approved. We, therefore, performed network meta-analysis (NMA) to identify and compare the efficacy of medications for primary breast cancer prevention.

METHODS: We performed a literature search completed on November 16, 2023, in Embase, Ovid-Medline, Scopus, and Cochrane Library for randomized controlled trials (RCTs) evaluating risk-reducing medications in women without a history of invasive breast cancer. Two reviewers independently screened and extracted data based on predefined criteria, following the Preferred …

Eculizumab Treatment Of Tacrolimus-Associated Autoimmune Haemolytic Anaemia And Thrombotic Microangiopathy In A Child With Orthotopic Heart Transplant, Daniel Pike, Monica Hulbert, Alicia Kamsheh

2020-Current year OA Pubs

BACKGROUND: Tacrolimus is the standard immunosuppressant used in paediatric orthotopic heart transplantation, but it can be associated with rare and life-threatening haemolysis.

METHODS: Retrospective chart review was used for this case report.

RESULTS/CONCLUSION: We present the case of a 6-year-old heart transplant recipient who developed life-threatening haemolysis in the setting of mycoplasma infection while on tacrolimus immunosuppression that was treated successfully with eculizumab.

Factors Associated With Self-Report Symptom Screening Adherence In Pediatric Cancer Patients, L Lee Dupuis, Allison A King, Lisa M Klesges, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Objective was to describe the association between baseline characteristics and the number of Symptom Screening in Pediatrics Tool (SSPedi) assessments completed over an 8-week period.

METHODS: This was a sub-analysis of a cluster randomized controlled trial among 10 sites that were randomized to the intervention group. Participants were English- or Spanish-speaking pediatric patients 8-18 years of age newly diagnosed with cancer. Participants were prompted to complete SSPedi three times weekly for 8 weeks. The outcome was the number of SSPedi assessments completed during the 8-week period. Factors associated with the number of assessments were determined using mixed effects Poisson …

Cardiac Transplantation Does Not Improve Exercise Tolerance, Muscle Mass, Or Substrate Metabolism In Barth Syndrome, W Todd Cade, Kathryn L Bohnert, Linda R Peterson, Lisa De Las Fuentes, Emily Poehlein, Cynthia L Green, Christina A Pacak, Barry J Byrne, Dominic N Reeds, Adil Bashir, Brian Feingold, Carolyn Taylor

2020-Current year OA Pubs

Barth syndrome (BTHS) is a rare X-linked recessive disorder characterized by mutations in the TAFAZZIN gene, leading to mitochondrial dysfunction, cardioskeletal myopathy, neutropenia, exercise intolerance, and growth delay. While cardiac transplantation can improve heart function in BTHS patients, the metabolic effects of this procedure remain poorly understood. This study aimed to compare skeletal muscle morphology, substrate metabolism, energetics, and exercise tolerance in individuals with BTHS who had undergone cardiac transplantation (BTHS-T) versus BTHS patients without transplantation (BTHS-noT) and healthy controls. Six (

Molecular Profile Of Adult Primary Leptomeningeal Gliomatosis Aligns With Glioblastoma, Idh-Wildtype, Yi Zhu, Darin D Carabenciov, Derek R Johnson, Jorge A Trejo-Lopez, Aivi T Nguyen, Aditya Raghunathan, Giuseppe Lanzino, Cristiane M Ida, Cinthya J Zepeda-Mendoza, Surendra Dasari, Emilie Russler-Germain, Sonika Dahiya, Martha Quezado, Kenneth Aldape, Caterina Giannini

2020-Current year OA Pubs

Adult primary leptomeningeal gliomatosis (PLG) is a rare, rapidly progressive and fatal disease characterized by prominent leptomeningeal infiltration by a glial tumor without an identifiable parenchymal mass. The molecular profile of adult PLG has not been well-characterized. We report the clinical, pathological, and molecular findings of six adult PLG patients (five males and one female), median age 58 years. All cases exhibited pathological leptomeningeal enhancement at presentation. Leptomeningeal biopsy was diagnostic in five (of six) cases, revealing infiltration by an astrocytic glioma with mitotic activity, lacking microvascular proliferation or necrosis. One case was diagnosed at autopsy. All tumors were IDH-wildtype, …

Kpna2 Promotes Osteosarcoma Progression By Regulating The Alternative Splicing Of Ddx3x Mediated By Ybx1, Li Cao, Ke Jia, B A Van Tine, Yihan Yu, Yizhong Peng, Xuanzuo Chen, Qing Pan, Wenbo Yang, Zhicai Zhang, Zengwu Shao, Wei Wu

2020-Current year OA Pubs

Osteosarcoma (OS) is a rapidly progressive primary malignant bone tumor that occurs in children and adolescents aged between 15 and 19 years and adults aged over 60 years. As alternative splicing (AS) changes caused by abnormal splicing factors contribute to tumor progression, gene expression and AS analyses were performed on 44 osteosarcoma patients to create a genome-wide co-expression network of RNA-binding proteins (RBPs), AS events, and AS genes. A gain- or loss-of-function osteosarcoma cell model was established, and an interactive network analysis and enrichment analysis were performed. Karyopherin Subunit Alpha 2 (KPNA2) negatively correlated with patient survival. KPNA2 transports splicing …

Choroid Plexus Apocrine Secretion Shapes Csf Proteome During Mouse Brain Development, Ya'el Courtney, Joshua P Head, Neil Dani, Olga V. Chechneva, Frederick B Shipley, Yong Zhang, Michael J Holtzman, Cameron Sadegh, Towia A Libermann, Maria K Lehtinen

2020-Current year OA Pubs

The choroid plexus (ChP) regulates cerebrospinal fluid (CSF) composition, providing essential molecular cues for brain development; yet, embryonic ChP secretory mechanisms remain poorly defined. Here we identify apocrine secretion by embryonic ChP epithelial cells as a key regulator of the CSF proteome and neurodevelopment in male and female mice. We demonstrate that the activation of serotonergic 5-HT

Polygenic Prediction Of Body Mass Index And Obesity Through The Life Course And Across Ancestries, Roelof A J Smit, Lihua Wang, Mary F. Feitosa, Michael A. Province, Dabeeru C. Rao, Adam E. Locke, Et Al.

2020-Current year OA Pubs

No abstract provided.

Molecular Mechanisms Of Inverse Agonism Via Κ-Opioid Receptor-G Protein Complexes, Aaliyah S Tyson, Saif Khan, Zenia Motiwala, Gye Won Han, Zixin Zhang, Mohsen Ranjbar, Daniel Styrpejko, Nokomis Ramos-Gonzalez, Stone Woo, Kelly Villers, Delainey Landaker, Terry Kenakin, Ryan Shenvi, Susruta Majumdar, Cornelius Gati

2020-Current year OA Pubs

Opioid receptors, a subfamily of G protein-coupled receptors (GPCRs), are key therapeutic targets. In the canonical GPCR activation model, agonist binding is required for receptor-G protein complex formation, while antagonists prevent G protein coupling. However, many GPCRs exhibit basal activity, allowing G protein association without an agonist. The pharmacological impact of agonist-free receptor-G protein complexes is poorly understood. Here we present biochemical evidence that certain κ-opioid receptor (KOR) inverse agonists can act via KOR-G

Sleep Variability And Time To Achieving Pregnancy: Findings From A Pilot Cohort Study Of Women Desiring Pregnancy, Peinan Zhao, Emily S Jungheim, Bronwyn S Bedrick, Leping Wan, Patricia T Jimenez, Ronald Mccarthy, Jessica Chubiz, Justin C Fay, Erik D Herzog, Siobhan Sutcliffe, Sarah K England

2020-Current year OA Pubs

OBJECTIVE: To determine whether chronodisruption is associated with achieving pregnancy.

DESIGN: Pilot prospective cohort study.

SETTING: Academic Medical Center.

SUBJECTS: One hundred eighty-three women desiring pregnancy were recruited from the local community of an academic medical center located in the Midwest and provided sleep information between February 1, 2015, and November 30, 2017.

EXPOSURE: Sleep and activity data were obtained via actigraphy watches worn continuously for 2 weeks to assess measures of chronodisruption, including sleep period onset, offset, midtime, and duration; as well as variability in each of these measures.

MAIN OUTCOME MEASURES: Time to becoming pregnant over 1-year of …

Reduced Risk Of Cesarean Delivery With Oxytocin Discontinuation In Active Labor: A Systematic Review And Meta-Analysis, Julia Whitley, Julia Burd, Michelle Doering, Jeannie Kelly, Antonina Frolova, Nandini Raghuraman

2020-Current year OA Pubs

OBJECTIVE: Our objective was to determine if oxytocin discontinuation in the active phase of labor impacts the rate of cesarean delivery compared to continuation of oxytocin.

DATA SOURCES: This study was a systematic review and meta-analysis of randomized controlled trials. A research librarian performed a database search using a combination of standardized terms and keywords related to oxytocin discontinuation and stages of labor from database inception until February 2024. This protocol was registered in The International Prospective Register of Systematic Reviews (PROSPERO).

STUDY ELIGIBILITY CRITERIA: Randomized controlled trials of pregnant patients who received oxytocin for induction or augmentation of labor, …

Liger-Hn Phase Iii Trials Of Petosemtamab + Pembrolizumab And Petosemtamab Monotherapy In Recurrent Or Metastatic Hnscc, Jean-Pascal Machiels, Douglas Adkins, Et Al.

2020-Current year OA Pubs

Patients with recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC) have limited treatment options and a dismal prognosis, especially when their cancer is resistant to standard treatments like anti-programmed cell death protein 1 and platinum-based therapies. Petosemtamab - a human, common light chain, bispecific antibody with enhanced antibody-dependent cellular cytotoxicity targeting epidermal growth factor receptor (EGFR) and leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) - demonstrated antitumor activity in r/m HNSCC. In many tumor types, including HNSCC, EGFR is an oncogenic driver, while LGR5 is upregulated. LGR5 can potentiate the wingless-type integration site (WNT)/β-catenin signaling pathway in response to …

Mayo Normative Studies: Regression-Based Normative Data For Remote Self-Administration Of The Stricker Learning Span, Symbols Test, And Mayo Test Drive Screening Battery Composite And Validation In Individuals With Mild Cognitive Impairment And Dementia, Nikki H Stricker, Jason Hassenstab, Et Al.

2020-Current year OA Pubs

No abstract provided.

Projection-Tags Enable Multiplex Projection Tracing And Multi-Modal Profiling Of Projection Neurons, Lite Yang, Fang Liu, Hannah Hahm, Takao Okuda, Xiaoyue Li, Yufen Zhang, Vani Kalyanaraman, Monique R Heitmeier, Vijay K Samineni

2020-Current year OA Pubs

Single-cell multiomic techniques have sparked immense interest in developing a comprehensive multi-modal map of diverse neuronal cell types and their brain-wide projections. However, investigating the complex wiring diagram, spatial organization, transcriptional, and epigenetic landscapes of brain-wide projection neurons is hampered by the lack of efficient and easily adoptable tools. Here we introduce Projection-TAGs, a retrograde AAV platform that allows multiplex tagging of projection neurons using RNA barcodes. By using Projection-TAGs, we performed multiplex projection tracing of the cortex and high-throughput single-cell profiling of the transcriptional and epigenetic landscapes of the cortical projection neurons in female mice. Projection-TAGs can be leveraged …

Determining Falls Risk In People With Parkinson's Disease Using Wearable Sensors: A Systematic Review, Maeve Bradley, Sarah O'Loughlin, Eoghan Donlon, Amy Gallagher, Clodagh O'Keeffe, John Inocentes, Federica Ruggieri, Richard B Reilly, Richard Walsh, Tim Lynch, Daniel G Di Luca, Conor Fearon

2020-Current year OA Pubs

A prior history of falls remains the strongest predictor of future falls in individuals with Parkinson's disease (PD). There are limited biomarkers available to identify falls risk before falls begin to occur. The aim of this review is to investigate if features associated with falls risk may be detected by wearable sensors in patients with PD. A systematic search of the MEDLINE, EMBASE, Cochrane, and Cinahl databases was performed. Key quality criteria include sample size adequacy, data collection procedures, and the clarity of statistical analyses. The data from each included study were extracted into defined data extraction spreadsheets. Results were …

Comparison Of Clinical Features And Outcomes Of Chinese Patients With Takotsubo Syndrome And Acute Myocardial Infarction- Results From The First Chinese Takotsubo Syndrome Registry, Yuxi Huang, Kan Liu, Et Al.

2020-Current year OA Pubs

BACKGROUND: Takotsubo syndrome (TTS) differs significantly from acute myocardial infarction (AMI) in clinical features and pathological mechanisms, but evidence in Asian populations remains limited. The aim of this study is to compare clinical features and outcomes between patients with TTS and AMI in the first Chinese registry of TTS (ChiTTS Registry, ChiCTR1900026725).

METHODS: In this multicenter 6-year retrospective cohort study (February 2016-June 2022), a total of 116 consecutive TTS patients diagnosed according to the international Takotsubo diagnostic criteria and 232 age- and sex-matched AMI patients (1:2 ratio) meeting the 2023 European Society of Cardiology guidelines criteria were enrolled from 10 …

Evolution And Predictors Of Right Ventricular Failure In Fontan Patients: A Case-Control Study, Hannah S Kim, Ginnie Abarbanell, Kathleen Simpson, Aaron M Abarbanell, Pirooz Eghtesady, Philip T Levy, Gautam K Singh

2020-Current year OA Pubs

No abstract provided.

Cannabis Use In Women And Sexual Dysfunction, Becky K. Lynn, Julia D. López, Morgan E. Link, E C. Campian

2020-Current year OA Pubs

No abstract provided.

What Drives Clinic Follow-Up After Traumatic Spinal Injury? An Observational Cohort Study From Tanzania, Chibuikem A Ikwuegbuenyi, Julie Woodfield, Romani Roman Sabas, Sean Inzerillo, Noah Willett, Magalie Cadieux, Scott L Zuckerman, Francois Waterkeyn, Halinder S Mangat, Hamisi K Shabani, Roger Härtl

2020-Current year OA Pubs

OBJECTIVES: To evaluate factors associated with clinic follow-up after traumatic spinal injury (TSI) in Tanzania, focusing on demographic, injury-related and hospital variables. We hypothesised that socioeconomic and injury-specific factors would predict follow-up adherence.

DESIGN: Retrospective observational cohort study.

SETTING: Tertiary government referral centre for neurosurgery and orthopaedics in Dar es Salaam, Tanzania.

PARTICIPANTS: 443 adults with TSI admitted between September 2016 and October 2021. Inclusion criteria included survival to discharge and availability of the discharge date. Patients with missing data were excluded.

PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes were any clinic follow-up and 1-year follow-up post-discharge. Secondary outcome was …

Low Frequency, High Complexity: Assessing Skill Decay In Transesophageal Echocardiography Post-Simulation Training, Enyo Ablordeppey, Emily Terian, Collyn T Murray, Laura Wallace, Wendy Huang, Erica Blustein, Alexander Croft, Ernesto Romo, Mansi Agarwal, Daniel Theodoro

2020-Current year OA Pubs

INTRODUCTION: Resuscitative transesophageal echo (rTEE) is a promising adjunct to cardiac arrest resuscitation. However, it is a high-acuity diagnostic tool that is rarely used in this setting and its safety establishment is limited because of low occurrence. High-acuity, low occurrence skills such as rTEE during cardiac arrest inevitably decay. In this study we examined the content and percentage of rTEE skill decay following simulation-based education (SBE).

METHODS: Resuscitative TEE-naïve emergency physicians (EP) were trained using a combination of clinical exposure, web-based didactics, and monthly hands-on sessions with a high-fidelity rTEE simulator for four months. The COVID-19 pandemic created a natural …

Metabolic Control Of Glycosylation Forms For Establishing Glycan-Dependent Protein Interaction Networks, Xingyu Liu, Li Yi, Zongtao Lin, Siyu Chen, Shunyang Wang, Ying Sheng, Carlito B Lebrilla, Benjamin A Garcia, Yixuan Xie

2020-Current year OA Pubs

Protein-protein interactions (PPIs) are crucial for comprehending the molecular mechanisms and signaling pathways underlying diverse biological processes and disease progression. However, investigating PPIs involving membrane proteins is challenging due to the complexity and heterogeneity of glycosylation. To tackle this challenge, we developed an approach termed glycan-dependent affinity purification coupled with mass spectrometry (GAP-MS), specifically designed to characterize changes in glycoprotein PPIs under varying glycosylation conditions. GAP-MS integrates metabolic control of glycan profiles in cultured cells using small molecules referred to as glycan modifiers with affinity purification followed by mass spectrometry analysis (AP-MS). Here, GAP-MS was applied to characterize and compare …

Apolipoprotein M Attenuates Age-Related Macular Degeneration Phenotypes Via Sphingosine-1-Phosphate Signaling And Lysosomal Lipid Catabolism, Tae Jun Lee, Andrea Santeford, Kristen M Pitts, Carla Valenzuela Ripoll, Ryo Terao, Zhen Guo, Mualla Ozcan, Dagmar Kratky, Christina Christoffersen, Ali Javaheri, Rajendra S Apte

2020-Current year OA Pubs

Age-related macular degeneration (AMD) is a leading cause of blindness in people over 50. AMD and cardiovascular disease share risk factors including age, impaired lipid metabolism, and extracellular lipid deposition. Because of its importance in age-related diseases, we hypothesize that apolipoprotein M (ApoM), a lipocalin that binds sphingosine-1-phosphate (S1P), might restore lipid homeostasis and retinal function in AMD. In support, we find that human patients with AMD demonstrate significantly reduced ApoM compared to controls. In mice with impaired retinal cholesterol efflux, ApoM improves retinal pigment epithelium (RPE) function and lipotoxicity in an S1P- and S1P receptor 3-dependent manner. Ultrastructural evidence …