Ophthalmology Commons^™

Dapk2 Regulates Pkm2 Phosphorylation At Threonine 45 To Facilitate Disturbed Flow-Induced Atherosclerosis, Shuai Guo, Long Xu, Yixin Chen, Yuan Zhao, Yuting Zhang, Runfa Yu, Kaixiang Cao, Litao Wang, Wenjia Ai, Jiang-Yun Luo, Lu Lu, Jun He, Yuan Zhou, Li Wang, Andrew H Baker, Yuqing Huo, Yiming Xu

Faculty, Staff and Students Publications

Background: Oscillatory shear stress (OSS), resulting from disturbed blood flow, is implicated in atherosclerotic plaque formation by incompletely understood mechanisms. This study aims to elucidate the involvement of death-associated protein kinase (DAPK) 2 in OSS-induced endothelial cell (EC) activation and atherosclerosis.

Methods: Publicly available resources, including genome-wide microarray, RNA sequencing, and single-cell RNA sequencing, were utilized to identify key OSS-sensitive regulatory factors. Techniques such as mass spectrometry, immunoprecipitation, proximity ligation assay, and RNA sequencing were employed to identify pyruvate kinase M2 (PKM2) as the binding protein of DAPK2 and determine the specific site of PKM2 phosphorylation by DAPK2. To assess …

Endothelial Micu1 Protects Against Vascular Inflammation And Atherosclerosis By Inhibiting Mitochondrial Calcium Uptake, Lu Sun, Ruixue Leng, Monan Liu, Meiming Su, Qingze He, Zhidan Zhang, Zhenghong Liu, Zhihua Wang, Hui Jiang, Li Wang, Shuai Guo, Yiming Xu, Yuqing Huo, Clint L Miller, Maciej Banach, Yu Huang, Paul C Evans, Jaroslav Pelisek, Giovanni G Camici, Bradford C Berk, Stefan Offermanns, Junbo Ge, Suowen Xu, Jianping Weng

Faculty, Staff and Students Publications

Mitochondrial dysfunction fuels vascular inflammation and atherosclerosis. Mitochondrial calcium uptake 1 (MICU1) maintains mitochondrial Ca2+ homeostasis. However, the role of MICU1 in vascular inflammation and atherosclerosis remains unknown. Here, we report that endothelial MICU1 prevents vascular inflammation and atherosclerosis by maintaining mitochondrial homeostasis. We observed that vascular inflammation was aggravated in endothelial cell–specific Micu1 knockout mice (Micu1ECKO) and attenuated in endothelial cell–specific Micu1 transgenic mice (Micu1ECTg). Furthermore, hypercholesterolemic Micu1ECKO mice also showed accelerated development of atherosclerosis, while Micu1ECTg mice were protected against atherosclerosis. Mechanistically, MICU1 depletion increased mitochondrial Ca2+ influx, thereby decreasing the expression …

The Role Of Inflammation In Diabetic Retinopathy In Patients With Type Ii Diabetes; Potential Therapeutic Perspectives, Adriana Georgescu, Ana Dascalu, Daniela Stana, Cristina Alexandrescu, Anca Bobirca, Bogdan Mihai Cristea, Geta Vancea, Crenguta Sorina Serboiu, Dragos Serban, Corneliu Tudor, Andreea Letitia Arsene, Laura Carina Tribus

Journal of Mind and Medical Sciences

Diabetic retinopathy is one of the major causes of visual impairment and blindness in adult population. The pathology is complex, the metabolic changes induced by the hyperglycemic environment leading to neurodegeneration, microvascular damage, with secondary ischemic and inflammatory changes in the retina. This review aims to update the literature data related to the role of inflammation in the onset and progression of diabetic retinopathy. Thus, the molecular and biochemical mechanisms triggered by excess glucose increase the expression of genes involved in inflammatory processes, which leads to the synthesis of inflammatory cytokines such as Il1, Il6, TNF alpha as well as …

A Double-Blind, Randomized Controlled Study Of The Effects Of Celecoxib On Clinical Symptoms And Cognitive Impairment In Patients With Drug-Naïve First Episode Schizophrenia: Pharmacogenetic Impact Of Cyclooxygenase-2 Functional Polymorphisms, Dong-Mei Wang, Da-Chun Chen, Mei-Hong Xiu, Li Wang, Thomas R Kosten, Xiang-Yang Zhang

Faculty, Staff and Students Publications

Chronic low-grade peripheral and central nervous system inflammation may have a role in the pathogenesis of schizophrenia (SCZ). Inhibition of cyclooxygenase-2 (COX2), the arachidonic acid pathway, may inhibit cytokine responses and minimize inflammation. In this study, we added the COX2 inhibitor celecoxib to risperidone monotherapy to examine its efficacy on clinical symptoms and cognitive deficits in drug-naïve first episode (DNFE) SCZ patients. First, we genotyped two polymorphisms (rs5275 and rs689466) in the COX-2 gene in a case-control study of 353 SCZ patients and 422 healthy controls. Ninety patients participated in a 12-week, double-blind, randomized, placebo-controlled trial of celecoxib 400 mg/day. …

Ectoine, From A Natural Bacteria Protectant To A New Treatment Of Dry Eye Disease, Xin Chen, Na Lin, Jin-Miao Li, Haixia Liu, Anmar Abu-Romman, Ebru Yaman, Fang Bian, Cintia S De Paiva, Stephen C Pflugfelder, De-Quan Li

Faculty, Staff and Students Publications

Ectoine, a novel natural osmoprotectant, protects bacteria living in extreme environments. This study aimed to explore the therapeutic effect of ectoine for dry eye disease. An experimental dry eye model was created in C57BL/6 mice exposed to desiccating stress (DS) with untreated mice as controls (UT). DS mice were dosed topically with 0.5-2.0% of ectoine or a vehicle control. Corneal epithelial defects were detected via corneal smoothness and Oregon Green dextran (OGD) fluorescent staining. Pro-inflammatory cytokines and chemokines were evaluated using RT-qPCR and immunofluorescent staining. Compared with UT mice, corneal epithelial defects were observed as corneal smoothness irregularities and strong …

Exploring Angiotensin Ii And Oxidative Stress In Radiation-Induced Cataract Formation: Potential For Therapeutic Intervention, Vidya P. Kumar, Yali Kong, Riana Dolland, Sandra R. Brown, Kan Wang, Damian Dolland, David Mu, Milton L. Brown

Department of Biomedical and Translational Sciences Faculty Publications

Radiation-induced cataracts (RICs) represent a significant public health challenge, particularly impacting individuals exposed to ionizing radiation (IR) through medical treatments, occupational settings, and environmental factors. Effective therapeutic strategies require a deep understanding of the mechanisms underlying RIC formation (RICF). This study investigates the roles of angiotensin II (Ang II) and oxidative stress in RIC development, with a focus on their combined effects on lens transparency and cellular function. Key mechanisms include the generation of reactive oxygen species (ROS) and oxidative damage to lens proteins and lipids, as well as the impact of Ang II on inflammatory responses and cellular apoptosis. …

Inflammation And Fibrosis In Orbital Inflammatory Disease: A Histopathologic Analysis., Rohan Verma, Allison J Chen, Dongseok Choi, David J Wilson, Hans E Grossniklaus, Roger A Dailey, John D Ng, Eric A Steele, Stephen R Planck, Craig N Czyz, Bobby S Korn, Don O Kikkawa, Jill A Foster, Michael Kazim, Gerald J Harris, Deepak P Edward, Azza Al Maktabi, James T Rosenbaum

Surgery Articles

PURPOSE: The purpose of this study was to compare the histopathologic inflammation and fibrosis of orbital adipose tissue in orbital inflammatory disease (OID) specimens.

METHODS: In this retrospective cohort study, inflammation, and fibrosis in orbital adipose tissue from patients with thyroid-associated orbitopathy (TAO), granulomatosis with polyangiitis (GPA), sarcoidosis, nonspecific orbital inflammation (NSOI), and healthy controls were scored by 2 masked ocular pathologists. Both categories were scored on a scale of 0 to 3 with scoring criteria based on the percentage of specimens containing inflammation or fibrosis, respectively. Tissue specimens were collected from oculoplastic surgeons at 8 international centers representing 4 …

The Role Of Inflammation In Age-Related Macular Degeneration, Diana Florina Tricorache, Ana Maria Dascalu, Crenguta Serboiu, Anca Bobirca, Dragos Cretoiu, Dan Bratu, Corneliu Tudor, Laura Carina Tribus

Journal of Mind and Medical Sciences

Age-related macular degeneration (AMD) is a complex, chronic, and progressive disease which affects the macular area, being one of the leading causes of irreversible vision loss worldwide. Specific alterations of retinal structure occur at the macular level, which regarding its severity can range from the presence of drusen to the development of geographic atrophy or choroidal neovascularization. AMD has long been considered a degenerative disease, but new studies highlight the role of inflammation present both in the atrophic form and in the exudative form. The present review is based on comprehensive research on PubMed and Web of Science databases, and …

Tnf Is A Critical Cytokine In Age-Related Dry Eye Disease, Yashaswini Kelagere, Kaitlin K Scholand, Erica N Dejong, Andrea I Boyd, Zhiyuan Yu, Roger A Astley, Michelle C Callegan, Dawn Me Bowdish, Helen P Makarenkova, Cintia S De Paiva

Faculty, Staff and Students Publications

Aging is a complex biological process that is characterized by low-grade inflammation, called inflammaging. Aging affects multiple organs including eye and lacrimal gland. Tumor necrosis factor (TNF) is a pleiotropic cytokine that participates in inflammation, activation of proteases such as cathepsin S, and formation of ectopic lymphoid organs. Using genetic and pharmacological approaches, we investigated the role of TNF in age-related dry eye disease, emphasizing the ocular surface and lacrimal gland inflammation. Our results show the increased protein and mRNA levels of TNF in aged lacrimal glands, accompanied by increased TNF, IL1β, IL-18, CCL5, CXCL1, IL-2, IL-2 receptor alpha (CD25), …

Demodex Blepharitis: A Comprehensive Review Of The Disease, Current Management, And Emerging Therapies, Michelle K. Rhee, Elizabeth Yeu, Melissa Barnett, Christopher J. Rapuano, Deepinder K Dhaliwal, Kelly K. Nichols, Paul Karpecki, Francis S. Mah, Arthur Chan, James Mun, Ian Benjamin Gaddie

Wills Eye Hospital Papers

Demodex blepharitis is a common disease of the eyelid, affecting approximately 25 million Americans. This article reviews what is known about the mechanisms and impact of Demodex blepharitis, risk factors, signs and symptoms, diagnostic techniques, current management options, and emerging treatments. Demodex mites contribute to blepharitis in several ways: direct mechanical damage, as a vector for bacteria, and by inducing hypersensitivity and inflammation. Risk factors for Demodex blepharitis include increasing age, rosacea, and diabetes. The costs, symptom burden, and psychosocial effects of Demodex blepharitis are considerable. The presence of collarettes is pathognomonic for Demodex blepharitis. Redness, dryness, discomfort, foreign body …

An Ocular Th1 Immune Response Promotes Corneal Nerve Damage Independently Of The Development Of Corneal Epitheliopathy, Alexia Vereertbrugghen, Manuela Pizzano, Florencia Sabbione, Irene Angelica Keitelman, Carolina Maiumi Shiromizu, Douglas Vera Aguilar, Federico Fuentes, Cintia S De Paiva, Mirta Giordano, Analía Trevani, Jeremías G Galletti

Faculty, Staff and Students Publications

Proper sight is not possible without a smooth, transparent cornea, which is highly exposed to environmental threats. The abundant corneal nerves are interspersed with epithelial cells in the anterior corneal surface and are instrumental to corneal integrity and immunoregulation. Conversely, corneal neuropathy is commonly observed in some immune-mediated corneal disorders but not in others, and its pathogenesis is poorly understood. Here we hypothesized that the type of adaptive immune response may influence the development of corneal neuropathy. To test this, we first immunized OT-II mice with different adjuvants that favor T helper (Th)1 or Th2 responses. Both Th1-skewed mice (measured …

Extracellular-Vesicle-Based Therapeutics In Neuro-Ophthalmic Disorders, Hamed Massoumi, Sohil Amin, Mohammad Soleimani, Bita Momenaei, Mohammad Javad Ashraf, Victor H Guaiquil, Peiman Hematti, Mark I Rosenblatt, Ali R Djalilian, Elmira Jalilian

Wills Eye Hospital Papers

Extracellular vesicles (EVs) have been recognized as promising candidates for developing novel therapeutics for a wide range of pathologies, including ocular disorders, due to their ability to deliver a diverse array of bioactive molecules, including proteins, lipids, and nucleic acids, to recipient cells. Recent studies have shown that EVs derived from various cell types, including mesenchymal stromal cells (MSCs), retinal pigment epithelium cells, and endothelial cells, have therapeutic potential in ocular disorders, such as corneal injury and diabetic retinopathy. EVs exert their effects through various mechanisms, including promoting cell survival, reducing inflammation, and inducing tissue regeneration. Furthermore, EVs have shown …

The Circadian E3 Ligase Fbxl21 Regulates Myoblast Differentiation And Sarcomere Architecture Via Myoz1 Ubiquitination And Nfat Signaling, Bo Hu, Jian-Xing Ma, Adam S Duerfeldt

Faculty, Staff and Student Publications

Diabetic retinopathy and age-related macular degeneration are common retinal diseases with shared pathophysiology, including oxidative stress-induced inflammation. Cellular mechanisms responsible for converting oxidative stress into retinal damage are ill-defined but have begun to clarify. One common outcome of retinal oxidative stress is mitochondrial damage and subsequent release of mitochondrial DNA into the cytosol. This leads to activation of the cGAS-STING pathway, resulting in interferon release and disease-amplifying inflammation. This review summarizes the evolving link between aberrant cGAS-STING signaling and inflammation in common retinal diseases and provides prospective for targeting this system in diabetic retinopathy and age-related macular degeneration. Further defining …

Comparison Of Efficacy And Inflammatory Response To Thermoconjunctivoplasty Performed With Cautery Or Pulsed 1460 Nm Laser, Rodrigo Guimaraes De Souza, David Huang, Scott Prahl, Lauren Nakhleh, Stephen C Pflugfelder

Faculty, Staff and Students Publications

Conjunctivochalasis is a degenerative condition of the conjunctiva that disrupts tear distribution and causes irritation. Thermoreduction of the redundant conjunctiva is required if symptoms are not relieved with medical therapy. Near-infrared laser treatment is a more controlled method to shrink the conjunctiva than thermocautery. This study compared tissue shrinkage, histology, and postoperative inflammation in thermoconjunctivoplasty performed on the mouse conjunctiva using either thermocautery or pulsed 1460 nm near-infrared laser irradiation. Three sets of experiments were performed on female C57BL/6J mice (

Lacrimal Gland Epithelial Cells Shape Immune Responses Through The Modulation Of Inflammasomes And Lipid Metabolism, Vanessa Delcroix, Olivier Mauduit, Menglu Yang, Amrita Srivastava, Takeshi Umazume, Cintia S De Paiva, Valery I Shestopalov, Darlene A Dartt, Helen P Makarenkova

Faculty, Staff and Students Publications

Lacrimal gland inflammation triggers dry eye disease through impaired tear secretion by the epithelium. As aberrant inflammasome activation occurs in autoimmune disorders including Sjögren's syndrome, we analyzed the inflammasome pathway during acute and chronic inflammation and investigated its potential regulators. Bacterial infection was mimicked by the intraglandular injection of lipopolysaccharide (LPS) and nigericin, known to activate the NLRP3 inflammasome. Acute injury of the lacrimal gland was induced by interleukin (IL)-1α injection. Chronic inflammation was studied using two Sjögren's syndrome models: diseased

Safety Of Lenadogene Nolparvovec Gene Therapy Over 5 Years In 189 Patients With Leber Hereditary Optic Neuropathy, Catherine Vignal-Clermont, Patrick Yu-Wai-Man, Nancy J. Newman, Valerio Carelli, Mark L. Moster, Valerie Biousse, Prem S. Subramanian, An-Guor Wang, Sean P. Donahue, Bart P. Leroy, Alfredo A. Sadun, Thomas Klopstock, Robert C. Sergott, Gema Rebolleda Fernandez, Bart K. Chwalisz, Rudrani Banik, Magali Taiel, Michel Roux, José-Alain Sahel

Wills Eye Hospital Papers

Purpose

To evaluate the safety profile of lenadogene nolparvovec (Lumevoq) in patients with Leber hereditary optic neuropathy.

Design

Pooled analysis of safety data from 5 clinical studies.

Methods

A total of 189 patients received single unilateral or bilateral intravitreal injections of a recombinant adeno-associated virus 2 (rAAV2/2) vector encoding the human wild-type ND4 gene. Adverse events (AEs) were collected throughout the studies, up to 5 years. Intraocular inflammation and increased intraocular pressure (IOP) were ocular AEs of special interest. Other assessments included ocular examinations, vector bio-dissemination, and systemic immune responses against rAAV2/2.

Results

Almost all patients (95.2%) received 9 × …

Frosted Branch Angiitis After Smallpox Vaccination, Kristen Collister, Sam S Dahr

Faculty, Staff and Student Publications

PURPOSE: To describe a patient presenting with frosted branch angiitis soon after small-pox vaccination.

OBSERVATIONS: Frosted branch angiitis (FBA) is an acute onset retinal vasculitis featuring prominent perivascular sheathing in otherwise healthy individuals. FBA has been associated with noninfectious and infectious etiologies. This report describes a twenty-year-old African American female who developed bilateral frosted branch angiitis one week after small-pox vaccination. At presentation, the patient had bilateral, para-central visual field defects and subjective visual disturbances. On dilated exam, the patient demonstrated diffuse vasculitis bilaterally. The patient's field defects and clinical exam responded dramatically to oral prednisone therapy.

CONCLUSIONS AND IMPORTANCE: …

Retained Lens Fragment Presenting 32 Years After Cataract Extraction, Thomas Tien, Marcos A Crespo, Tatyana Milman, Zeba Syed

Wills Eye Hospital Papers

Purpose: To report a patient with retained lens material presenting over three decades after initial cataract extraction with fluctuating corneal edema and intraocular inflammation.

Observations: A 66-year-old man presented with a first episode of decreased vision and photophobia 32 years after cataract extraction without intraocular lens implantation in the right eye. Slit lamp examination revealed a tan-colored oblong mass in the inferior angle, in addition to corneal edema and an anterior chamber reaction. The patient was aphakic with traumatic mydriasis, and accordingly it was noted that the mass shifted location between anterior and posterior chambers over subsequent evaluations. The anterior …

Gut-Derived Butyrate Suppresses Ocular Surface Inflammation, Laura Schaefer, Humberto Hernandez, Rosalind A Coats, Zhiyuan Yu, Stephen C Pflugfelder, Robert A Britton, Cintia S De Paiva

Faculty, Staff and Students Publications

Dry eye is a common ocular inflammatory disorder characterized by tear film instability and reduced tear production. There is increasing evidence that homeostasis of the ocular surface is impacted by the intestinal microbiome. We are interested in investigating the potential role of microbially produced small molecules in mediating the interaction between the intestinal microbiota and the ocular surface. One such molecule is butyrate, a short-chain fatty acid (SCFA) produced by certain members of the gut microbiota through fermentation of dietary fiber. Here we show that SCFA transporter SLC5A8 is expressed in vivo in murine conjunctival and corneal epithelium. Pre-treatment of …

Electroacupuncture Ameliorates Inflammatory Response Induced By Retinal Ischemia-Reperfusion Injury And Protects The Retina Through The Dor-Bdnf/Trkb Pathway, Runjie Guo, Yongjie Zhang, Yue Geng, Ping Chen, Tiantian Fu, Yong Xia, Ren Zhang, Yuan Zhu, Jingling Jin, Nange Jin, Hong Xu, Xuesong Tian

Faculty, Staff and Student Publications

Objectives: Retinal ischemia-reperfusion injury (RIRI) is the common pathological basis of many ophthalmic diseases in the later stages, and inflammation is the primary damage mechanism of RIRI. Our study aimed to assess whether electroacupuncture (EA) has a protective effect against RIRI and to elucidate its related mechanisms.

Methods: A high-intraocular pressure (HIOP) model was used to simulate RIRI in Wistar rats. EA was applied to the EA1 group [Jingming (BL1) + Shuigou (GV26)] and the EA2 group [Jingming (BL1) + Hegu (LI4)] respectively for 30 min starting immediately after the onset of reperfusion and repeated (30 min/time) at 12 h …

New, Potent, Small Molecule Agonists Of Tyrosine Kinase Receptors Attenuate Dry Eye Disease, Zhiyuan Yu, Shaon Joy, Tianxiong Mi, Ghasem Yazdanpanah, Kevin Burgess, Cintia S De Paiva

Faculty, Staff and Students Publications

Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin3 (NT-3) bind to tyrosine kinase (Trk) receptors, TrkA, TrkB, and TrkC, respectively. This study investigated the efficacy of novel molecule agonists of Trk receptors in an in vivo model of dry eye disease (DED). Small molecule TrkC agonist (C1) and a pan-Trk agonist (pan) were synthesized for this. C57BL/6J mice were subjected to desiccating stress (DS) and received bilateral eye drops of C1, pan, or vehicle (2x/day). Dry eye signs, inflammation and expression of corneal barrier function, and conjunctival goblet cell (GC) densities were measured as part of the DED …

Spatial Transcriptomics Of The Lacrimal Gland Features Macrophage Activity And Epithelium Metabolism As Key Alterations During Chronic Inflammation, Olivier Mauduit, Vanessa Delcroix, Takeshi Umazume, Cintia S De Paiva, Darlene A Dartt, Helen P Makarenkova

Faculty, Staff and Students Publications

The lacrimal gland (LG) is an exocrine gland that produces the watery part of the tear film that lubricates the ocular surface. Chronic inflammation, such as Sjögren’s syndrome (SS), is one of the leading causes of aqueous-deficiency dry eye (ADDE) disease worldwide. In this study we analyzed the chronic inflammation in the LGs of the NOD.B10Sn-H2b/J (NOD.H-2b) mice, a mouse model of SS, utilizing bulk RNAseq and Visium spatial gene expression. With Seurat we performed unsupervised clustering and analyzed the spatial cell distribution and gene expression changes in all cell clusters within the LG sections. Moreover, for the …

Role Of Interferon Gamma Release Assay In The Diagnosis And Management Of Mycobacterium Tuberculosis-Associated Uveitis: A Review, Samra Rahman, Muhammad Irfan, Rehman Siddiqui

Section of Pulmonary & Critical Care

Tuberculosis (TB)-associated uveitis is a common cause of infectious uveitis in the developing world. Diagnosis of TB uveitis remains a challenge. The role of interferon gamma release assays (IGRAs) is uncertain. Herein we summarise the available literature on the utility of IGRAs in the diagnosis and management of TB uveitis. We searched PubMed database from 1 August 2010 to 31 July 2020 using the following keywords alone and in combination: 'interferon-gamma release assay', 'QuantiFERON', 'T-SPOT.TB', 'TB uveitis', 'serpiginous like choroiditis', 'tuberculoma', 'TB vasculitis', 'TB panuveitis' and 'ocular tuberculosis'. Data from 58 relevant studies were collated. The review is focused on …

Lacrimal Gland Tumors In Turkey: Types, Frequency, And Outcomes., Yağmur Seda Yeşiltaş, Ahmet Kaan Gündüz, Esra Erden, Carol L. Shields

Wills Eye Hospital Papers

AIM: To evaluate the clinical, radiological, and treatment features of lacrimal gland tumors.

METHODS: Retrospective review of 99 eyes of 92 patients with lacrimal gland tumors diagnosed and managed in a single institution between January 1999 and March 2017. Clinical and radiological features, histopathology, treatment methods, and prognosis were evaluated.

RESULTS: The mean patient age was 40.3 (range: 7-80)y. The diagnosis was made histopathologically in 91 (91.9%) tumors and on a clinical and radiological basis in 8 (8.1%) tumors. Final diagnoses included idiopathic orbital inflammation (pseudotumor) in 46 (46.5%) lesions, pleomorphic adenoma in 14 (14.1%), adenoid cystic carcinoma in 12 …

Inflammation In The Pathogenesis Of Diabetic Retinopathy, Haoshen Shi

Wayne State University Dissertations

The general purpose of these studies is to investigate inflammation in diabetic retinopathy in an effort to identify key intervention points to develop as treatments. Firstly, we showed that the neuropeptide VIP displayed protective immunoregulatory effects on retinal endothelial cells cultured under high glucose conditions. This effect was carried out, in part through the VPAC2 receptor.

Next, we studied the β-adrenergic receptor agonist, Compound 49b, and its effect on the pro-resolving RvD1 pathway. Compound 49b was previously shown to suppress both inflammatory and apoptotic responses in DR. We demonstrated that Compound 49b rescued the high glucose-induced decrese in RvD1 and …

An Investigation Of Human Beta-Defensins And Cathelicidin Expression In Patients With Pterygium., Remzi Karadag, Nurettin Bayram, Serpil Oguztuzun, Huseyin Bayramlar, Busra Bozer, Gulcin Simsek, Christopher J Rapuano

Wills Eye Hospital Papers

PURPOSE: To investigate human beta-defensins (HBDs) and cathelicidin LL-37 (LL-37) expressions in patients with pterygium.

METHODS: In this retrospective consecutive case series, 26 pterygium specimens and 15 normal conjunctival specimens of 15 control subjects were in vestigated. Expressions of HBD-1, HBD-2, HBD-3, and LL-37 were assessed using immuno histochemical staining. A brown color in the cytoplasm and/or nuclei of epithelial cells indicated positive staining for HBDs and LL-37. For each antibody, the intensity of the reaction (negative [-], weak [1+], moderate [2+], or strong [3+]) was determined to describe the immunoreactions.

RESULTS: The median age was 52 years in both …

Human Igg1 Antibodies Suppress Angiogenesis In A Target-Independent Manner, Sasha Bogdanovich, Younghee Kim, Takeshi Mizutani, Reo Yasuma, Laura Tudisco, Valeria Cicatiello, Ana Bastos-Carvalho, Nagaraj Kerur, Yoshio Hirano, Judit Z. Baffi, Valeria Tarallo, Shengjian Li, Tetsuhiro Yasuma, Parthasarathy Arpitha, Benjamin James Fowler, Charles B. Wright, Ivana Apicella, Adelaide Greco, Arturo Brunetti, Menotti Ruvo, Annamaria Sandomenico, Miho Nozaki, Ryo Ijima, Hiroki Kaneko, Yuichiro Ogura, Hiroko Terasaki, Balamurali K. Ambati, Jeanette H. W. Leusen, Wallace Y. Langdon, Michael R. Clark, Bradley D. Gelfand, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Publications

Aberrant angiogenesis is implicated in diseases affecting nearly 10% of the world’s population. The most widely used anti-angiogenic drug is bevacizumab, a humanized IgG1 monoclonal antibody that targets human VEGFA. Although bevacizumab does not recognize mouse Vegfa, it inhibits angiogenesis in mice. Here we show bevacizumab suppressed angiogenesis in three mouse models not via Vegfa blockade but rather Fc-mediated signaling through FcγRI (CD64) and c-Cbl, impairing macrophage migration. Other approved humanized or human IgG1 antibodies without mouse targets (adalimumab, alemtuzumab, ofatumumab, omalizumab, palivizumab and tocilizumab), mouse IgG2a, and overexpression of human IgG1-Fc or mouse IgG2a-Fc, also inhibited angiogenesis in wild-type …

Pharmacotherapy For Uveitis: Current Management And Emerging Therapy., Robert J. Barry, Quan Dong Nguyen, Richard W. Lee, Philip I. Murray, Alastair K. Denniston

Journal Articles: Ophthalmology

Uveitis, a group of conditions characterized by intraocular inflammation, is a major cause of sight loss in the working population. Most uveitis seen in Western countries is noninfectious and appears to be autoimmune or autoinflammatory in nature, requiring treatment with immunosuppressive and/or anti-inflammatory drugs. In this educational review, we outline the ideal characteristics of drugs for uveitis and review the data to support the use of current and emerging therapies in this context. It is crucial that we continue to develop new therapies for use in uveitis that aim to suppress disease activity, prevent accumulation of damage, and preserve visual …

Vegf164-Mediated Inflammation Is Required For Pathological, But Not Physiological, Ischemia-Induced Retinal Neovascularization, Susumu Ishida, Tomohiko Usui, Kenji Yamashiro, Yuichi Kaji, Shiro Amano, Yuichiro Ogura, Tetsuo Hida, Yoshihisa Oguchi, Jayakrishna Ambati, Joan W. Miller, Evangelos S. Gragoudas, Yin-Shan Ng, Patricia A. D'Amore, David T. Shima, Anthony P. Adamis

Ophthalmology and Visual Science Faculty Publications

Hypoxia-induced VEGF governs both physiological retinal vascular development and pathological retinal neovascularization. In the current paper, the mechanisms of physiological and pathological neovascularization are compared and contrasted. During pathological neovascularization, both the absolute and relative expression levels for VEGF₁₆₄ increased to a greater degree than during physiological neovascularization. Furthermore, extensive leukocyte adhesion was observed at the leading edge of pathological, but not physiological, neovascularization. When a VEGF₁₆₄-specific neutralizing aptamer was administered, it potently suppressed the leukocyte adhesion and pathological neovascularization, whereas it had little or no effect on physiological neovascularization. In parallel experiments, genetically altered VEGF_{164 …}