Ophthalmology Commons^™

Vigabatrin-Induced Peripheral Visual Field Defects In Patients With Refractory Partial Epilepsy, Robert C. Sergott, Richard M. Bittman, Erin M. Christen, Stephen M. Sagar

Wills Eye Hospital Papers

Purpose:

Vigabatrin can cause retinopathy, resulting in bilateral visual field constriction. Previous analyses of results from a prospective, observational study assessing vigabatrin-induced visual field constriction (described below) employed a partially subjective interpretation of static perimetery. In an effort to affirm these previous findings through more objective, quantitative methodology, we now report data from a subset analysis of refractory partial epilepsy patients in the study who underwent Goldmann kinetic perimetry.

Methods:

Patients aged ≥8 years with refractory partial seizures were enrolled and grouped: those receiving vigabatrin for ≥6 months (Group I); those who had received vigabatrin for ≥6 months and then …

Calcium Regulates Vesicle Replenishment At The Cone Ribbon Synapse., Norbert Babai, Theodore M. Bartoletti, Wallace B. Thoreson

Journal Articles: Ophthalmology

Cones release glutamate-filled vesicles continuously in darkness, and changing illumination modulates this release. Because sustained release in darkness is governed by vesicle replenishment rates, we analyzed how cone membrane potential regulates replenishment. Synaptic release from cones was measured by recording postsynaptic currents in Ambystoma tigrinum horizontal or OFF bipolar cells evoked by depolarization of simultaneously voltage-clamped cones. We measured replenishment after attaining a steady state between vesicle release and replenishment using trains of test pulses. Increasing Ca(2+) currents (I(Ca)) by changing the test step from -30 to -10 mV increased replenishment. Lengthening -30 mV test pulses to match the Ca(2+) …

The Endogenous Soluble Vegf Receptor-2 Isoform Suppresses Lymph Node Metastasis In A Mouse Immunocompetent Mammary Cancer Model, Masa-Aki Shibata, Jayakrishna Ambati, Eiko Shibata, Romulo J. C. Albuquerque, Junji Morimoto, Yuko Ito, Yoshinori Otsuki

Ophthalmology and Visual Science Faculty Publications

BACKGROUND: Cancer metastasis contributes significantly to cancer mortality and is facilitated by lymphangiogenesis and angiogenesis. A new splicing variant, endogenous soluble vascular endothelial growth factor receptor-2 (esVEGFR-2) that we recently identified is an endogenous selective inhibitor of lymphangiogenesis. To evaluate the antimetastatic potential of esVEGFR-2, gene therapy with vector expressing esVEGFR-2 (pesVEGFR-2) or endostatin (pEndo) as a positive control was conducted on murine metastatic mammary cancer.

METHODS: Syngeneic inoculated metastatic mammary cancers received direct intratumoral injection of pesVEGFR-2, pEndo or pVec as control, once a week for six weeks. In vivo gene electrotransfer was performed on the tumors after each …

Obstructive Sleep Apnea And Ocular Disorders., Deepak P. Grover

Wills Eye Hospital Papers

PURPOSE OF REVIEW: Obstructive sleep apnea is a diagnosis that ophthalmologists can screen for when a patient presents with certain risk factors. Recent literature provides strong data for associations between sleep apnea and ocular disorders.

RECENT FINDINGS: A potentially serious disorder, sleep apnea can lead to many systemic and ocular complications. Recent findings provide data on the prevalence of sleep apnea with various disorders. Adequate treatment of sleep apnea has also shown to reverse both systemic and eye-related complications.

SUMMARY: Early diagnosis and management of sleep apnea is critical for reducing the risk of devastating systemic complications and preserving ocular …

Endothelial Cell Capture Of Heparin-Binding Growth Factors Under Flow, Bing Zhao, Changjiang Zhang, Kimberly Forsten-Williams, Jun Zhang, Michael Fannon

Ophthalmology and Visual Science Faculty Publications

Circulation is an important delivery method for both natural and synthetic molecules, but microenvironment interactions, regulated by endothelial cells and critical to the molecule's fate, are difficult to interpret using traditional approaches. In this work, we analyzed and predicted growth factor capture under flow using computer modeling and a three-dimensional experimental approach that includes pertinent circulation characteristics such as pulsatile flow, competing binding interactions, and limited bioavailability. An understanding of the controlling features of this process was desired. The experimental module consisted of a bioreactor with synthetic endothelial-lined hollow fibers under flow. The physical design of the system was incorporated …

Compositions And Methods For Inhibiting Drusen Complement Components C3a And C5a For The Treatment Of Age-Related Macular Degeneration, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Patents

Activated C3 (C3a) and its receptor (C3aR) and activated C5 (C5a) and its receptor (C5aR) have been shown to induce vascular endothelial growth factor (VEGF) expression in vitro and in vivo. Compositions and methods for inhibiting C3a, C3aR, C5a and C5aR for the treatment and/or prevention of neovascular disease are provided. Also provided are Novel therapeutic targets and diagnostic markers for choroidal neovascularization.

Vitamin D Binding Protein-Macrophage Activating Factor Directly Inhibits Proliferation, Migration, And Upar Expression Of Prostate Cancer Cells, Kalvin J. Gregory, Bing Zhao, Diane R. Bielenberg, Sami Dridi, Jason Wu, Weihua Jiang, Bin Huang, Steven Pirie-Shepherd, Michael Fannon

Ophthalmology and Visual Science Faculty Publications

BACKGROUND: Vitamin D binding protein-macrophage activating factor (DBP-maf) is a potent inhibitor of tumor growth. Its activity, however, has been attributed to indirect mechanisms such as boosting the immune response by activating macrophages and inhibiting the blood vessel growth necessary for the growth of tumors.

METHODS AND FINDINGS: In this study we show for the first time that DBP-maf exhibits a direct and potent effect on prostate tumor cells in the absence of macrophages. DBP-maf demonstrated inhibitory activity in proliferation studies of both LNCaP and PC3 prostate cancer cell lines as well as metastatic clones of these cells. Flow cytometry …

Primary Chiasmal Sarcoid Granuloma Masquerading As Glioma Of The Optic Chiasm, Muhammad Zubair Tahir, Farheen Shaikh, Arshad Ali Siddiqui

Section of Neurosurgery

A 37-year-old woman presented with a 6 months history of headaches and memory impairment. Examination showed no neurological deficit with normal vision. MRI scans showed an enlarged optic chiasm. There was no dural or leptomeningeal enhancement or hydrocephalus. Open biopsy of the suprasellar mass showed non-caseating chronic granulomatous inflammation compatible with sarcoidosis. Systemic features of sarcoid were absent. Patient showed marked improvement on steroid therapy.

Synthesis And Cyclic Voltammetry Of A2e, Elizabeth White, Willa Harper

Student Scholarship – Chemistry

As aging occurs, great exposure to light leads to the build-up of fluorescent materials called lipofuscin in the retinal pigment epithelial cells. This accumulation of lipofuscin is correlated to the progression of age related macular degeneration and other retinal dystrophies. No cure for macular degeneration has been found, so lipofuscin is of great interest. The lipofuscin has been associated with an increase in radiation intake and a loss of photoreceptors in the retina. The compound A2E is being studied in this project because it is frequently found in the lipofuscin. The goal of this project is to further characterize A2E …

Pediatric Ophthalmology And Strabismus: Something For Everyone., Alex V. Levin

Wills Eye Hospital Papers

This issue of Current Opinion in Ophthalmology highlights the uniquely broad range of pediatric ophthalmology and strabismus. Perhaps, unlike any other area of ophthalmology, our specialty covers virtually every part of the eye and a multitude of systemic disorders. Pediatric ophthalmology offers the practitioner the opportunity to impact a patient’s visual life for many decades giving them a lifetime of good vision. This issue of the journal highlights the many ways that this is so.

Convergence Insufficiency And Its Current Treatment., Judith B Lavrich

Wills Eye Hospital Papers

PURPOSE OF REVIEW: Considerable uncertainty and controversy has existed concerning the management of convergence insufficiency. Only recently there have been significant scientific studies published that compare the effectiveness of the commonly prescribed treatments. This paper reviews the most recent research and literature on convergence insufficiency and its treatment.

RECENT FINDINGS: The first large-scale placebo-controlled, randomized clinical trials to study the various treatments of convergence insufficiency have recently been published. Current research compares the effectiveness of base-in prism glasses, pencil push-ups, and vision therapy in reducing the signs and symptoms of convergence insufficiency and suggests that orthoptic therapy is the most …

Interferon Γ–Inducible Protein-10 (Ip-10) And Eotaxin As Biomarkers In Age-Related Macular Degeneration, F. M. Mo, A. D. Proia, W. H. Johnson, D. Cyr, K. Lashkari

Osteopathic Medicine, Jerry M. Wallace School of

No abstract provided.

Spontaneous Disconnection Of Glaucoma Tube Shunt Extenders., Oseluese Dawodu, Alex V. Levin

Wills Eye Hospital Papers

Glaucoma drainage implants are frequently used in children with severe forms of glaucoma, and tube extenders are sometimes required to compensate for ocular growth or when the intraocular portion of the tube is thought to be too short. We report 2 cases of spontaneous disconnection of a tube extender, occurring 8 months after insertion in one case and 3 years later in the other. In both cases the tube was removed and the patient treated with endoscopic diode laser photocoagulation.

Vasoactive Neuropeptides In Clinical Ophthalmology: An Association With Autoimmune Retinopathy?, Donald R. Staines, Ekua W. Brenu, Sonya Marshall-Gradisnik

Sonya Marshall-Gradisnik

The mammalian eye is protected against pathogens and inflammation in a relatively immune-privileged environment. Stringent mechanisms are activated that regulate external injury, infection, and autoimmunity. The eye contains a variety of cells expressing vasoactive neuropeptides (VNs), and their receptors, located in the sclera, cornea, iris, ciliary body, ciliary process, and the retina. VNs are important activators of adenylate cyclase, deriving cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP). Impairment of VN function would arguably impede cAMP production and impede utilization of ATP. Thus VN autoimmunity may be an etiological factor in retinopathy involving perturbations of purinergic signaling. A sound blood …

Management Of Devastating Ocular Trauma--Experience Of Maxillofacial Surgeons Deployed To A Forward Field Hospital, M. J. Ansell, J. Breeze, Vivian C. Mcalister, M. D. Williams

Surgery Publications

Combat-related eye injuries continue to increase in frequency and are generally secondary to Improvised Explosive Devices. Many ocular injuries are potentially preventable by the wearing of ballistic eye protection. The management of penetrating eye trauma is normally outside the routine practice of maxillofacial surgeons in the UK. The aim of this paper is to describe the surgical techniques used in the modern management of devastating ocular trauma including selected case examples managed by British military maxillofacial surgeons deployed to Afghanistan.

Cd4 T-Cell Suppression By Cells From Toxoplasma Gondii-Infected Retinas Is Mediated By Surface Protein Pd-L1, Elizabeth Charles, Sunil Joshi, John D. Ash, Barbara A. Fox

Dartmouth Scholarship

In the inflamed retina, CD4(+) T cells can cause retinal damage when they are not properly regulated. Since tissue expression of major histocompatibility complex (MHC) class II and costimulatory molecules is a key mechanism for regulating effector T cells, we tested the hypothesis that upregulation of these proteins in the retina contributes to the regulation of CD4 T cells. Here we report that in retinas infected with the protozoan parasite Toxoplasma gondii, MHC class II is upregulated on infiltrating leukocytes as well as on resident retinal cells, including photoreceptors. Flow cytometric analysis indicated that B7 costimulatory family members (CD80, CD86, …

The Assessment Of Disability Related To Vision Performance-Based Measure In Diabetic Retinopathy., Kevin J. Warrian, Luciano L. Lorenzana, Dara Lankaranian, Jyoti Dugar, Sheryl S. Wizov, George L. Spaeth

Wills Eye Hospital Papers

PURPOSE: To validate a third-generation performance-based measure of visual function titled "Assessment of Disability Related to Vision" (ADREV) in a study population of patients with diabetic retinopathy.

DESIGN: Prospective, cross-sectional study.

METHODS: Patients with nonproliferative or proliferative diabetic retinopathy, free from ocular comorbidity, were recruited from a single institute and completed the ADREV, the 25-Item National Eye Institute Visual Functioning Questionnaire (VFQ-25), and a clinical ophthalmic examination. Correlation, regression, and bootstrap analysis were conducted to determine the relationship between ADREV scoring and each of the study's clinical and self-report measures of visual ability, while controlling for potential confounders.

RESULTS: Ninety-one …

Anion-Sensitive Regions Of L-Type Cav1.2 Calcium Channels Expressed In Hek293 Cells., Norbert Babai, Nataly Kanevsky, Nathan Dascal, George J. Rozanski, Dhirendra P. Singh, Nigar Fatma, Wallace B. Thoreson

Journal Articles: Ophthalmology

L-type calcium currents (I(Ca)) are influenced by changes in extracellular chloride, but sites of anion effects have not been identified. Our experiments showed that CaV1.2 currents expressed in HEK293 cells are strongly inhibited by replacing extracellular chloride with gluconate or perchlorate. Variance-mean analysis of I(Ca) and cell-attached patch single channel recordings indicate that gluconate-induced inhibition is due to intracellular anion effects on Ca(2+) channel open probability, not conductance. Inhibition of CaV1.2 currents produced by replacing chloride with gluconate was reduced from approximately 75%-80% to approximately 50% by omitting beta subunits but unaffected by omitting alpha(2)delta subunits. Similarly, gluconate inhibition was …

Defensins In Ocular Immunity, Minhao Wu

Wayne State University Dissertations

Corneal infection with P. aeruginosa results in corneal perforation in susceptible

B6, but not resistant BALB/c mice. This study explored their role mBD 1-4 in corneal

infection, and their potential synergy. Immunostaining and real-time RT-PCR data

demonstrated that their expression was either constitutive (mBD1 and mBD2) or

inducible (mBD3 and mBD4) in normal BALB/c and B6 corneas, and disparately

regulated in BALB/c vs B6 corneas after infection. Knock down studies using siRNA

treatment indicated that mBD2 and mBD3, but neither mBD1 nor mBD4, is required in

ocular defense. Moreover, in vivo studies demonstrated individual and combined effects

of mBD2 and …

Identifying Factors Associated With Falls In Postmenopausal Breast Cancer Survivors: A Multi-Disciplinary Approach, Kerri M. Winters-Stone, Britta Torgrimson, Fay Horak, Alvin Eisner, Lillian Nail, Micahel C. Leo, Steve Chui, Shiuh-Wen Luoh

Community Health Faculty Publications and Presentations

Objective—To identify neuromuscular, balance and vision factors that contribute to falls in recently treated breast cancer survivors (BCS) and explore links between fall risk factors and cancer treatment

Design—Case-control plus prospective observation

Setting—Comprehensive cancer center

Participants—BCS within two years chemotherapy completion and/or on adjuvant endocrine therapy (N=59; mean age: 58 yrs)

Intervention—not applicable

Main outcome measures—Objective measures of postural control, vision and neuromuscular function included 1) a sensory organization test (SOT), 2) a visual assessment battery, 3) muscle mass by DXA, and 4) neuromuscular function with strength by repetition maximum, power by timed stair …

The Mozambique Eyecare Project: Implementing A Model That Addresses Uncorrected Refractive Error In Lusophone Africa., Stephen Thompson, Diane Wallace

Conference Papers

BACKGROUND

Optometric education and resources are drastically deficient in most of Africa, more so in Lusophone Africa where the problem is compounded by language barriers which isolate these countries from related developments in Africa and/or the developed world.

The Mozambique Eyecare Programme is a multi-partner collaboration between The International Centre for Eyecare Education (ICEE), Universidade Lúrio in Mozambique, Technological University Dublin, and the University of Ulster in Ireland, designed to address the need for optometric education in Lusophone Africa.

AIM

This paper aims to document the current situation with regards to human resource development in eyecare in Mozambique and offer …

Differential Gene Expression Profile Of Retinoblastoma Compared To Normal Retina., Arupa Ganguly, Carol L Shields

Wills Eye Hospital Papers

PURPOSE: The retinoblastoma gene (RB1) is a tumor suppressor gene that was first discovered in a rare ocular pediatric tumor called retinoblastoma (RB). The RB1 gene is essential for normal progression through the cell cycle and exerts part of its function through the family of transcription factors (E2F) and many other intermediaries. In the absence of normal RB1, genomic instability and chromosomal aberrations accumulate, leading to tumor initiation, progression, and ultimately metastasis. The purpose of this report was to identify the molecular pathways that are deregulated in retinoblastoma.

METHODS: We compared gene expression signatures of matched normal retinal tissue and …

Gene Delivery In The Equine Cornea: A Novel Therapeutic Strategy, Dylan G. Buss, Ajay Sharma, Elizabeth A. Giuliano, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—To determine if hybrid adeno-associated virus serotype 2/5 (AAV5) vector can effectively deliver foreign genes into the equine cornea without causing adverse side effects. The aims of this study were to: (i) evaluate efficacy of AAV5 to deliver therapeutic genes into equine corneal fibroblasts (ECFs) using enhanced green fluorescent protein (EGFP) marker gene and (ii) establish the safety of AAV5 vector for equine corneal gene therapy.

Animal Material—Primary ECF cultures were harvested from healthy donor equine corneas. Cultures were maintained at 370C in humidified atmosphere with 5% CO2.

Procedure—AAV5 vector expressing EGFP under control of hybrid cytomegalovirus (CMV) + chicken …

Vector Delivery Technique Affects Gene Transfer In The Cornea In Vivo, Rajiv R. Mohan, Ajay Sharma, Tyler C. Cebulko, Ashish Tandon

Pharmacy Faculty Articles and Research

Purpose: This study tested whether controlled drying of the cornea increases vector absorption in mouse and rabbit corneas in vivo and human cornea ex vivo, and studied the effects of corneal drying on gene transfer, structure and inflammatory reaction in the mouse cornea in vivo.

Methods: Female C57 black mice and New Zealand White rabbits were used for in vivo studies. Donor human corneas were used for ex vivo experiments. A hair dryer was used for drying the corneas after removing corneal epithelium by gentle scraping. The corneas received no, once, twice, thrice, or five times warm air for …

"Transduction Efficiency Of Aav 2/6, 2/8 And 2/9 Vectors For Delivering Genes In Human Corneal Fibroblasts ", Ajay Sharma, Arkasubhra Ghosh, Eric T. Hansen, Jason M. Newman, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

In the present study, cellular tropism and relative transduction efficiency of AAV2/6, AAV2/8 and AAV2/9 vectors have been tested for the cornea using primary cultures of human corneal fibroblasts. The AAV6, AAV8 and AAV9 serotypes having AAV2 ITR plasmid encoding for alkaline phosphatase (AP) gene were generated by transfecting HEK293 cell line with pHelper, pARAP4 and pRep/Cap plasmids. Primary cultures of human corneal fibroblasts were exposed to AAV infectious particles at two different doses (1×105 and 2×105 MOI). Cytochemistry and enzyme assays were used to measure delivered transgene expression in samples collected at 4 and 30 hours after AAV infection …

Role Of Transforming Growth Factor Beta In Corneal Function, Biology And Pathology, Ashish Tandon, Jonathan C. K. Tovey, Ajay Sharma, Rangan Gupta, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Transforming growth factor-beta (TGFβ) is a pleiotropic multifunctional cytokine that regulates several essential cellular processes in many parts of the body including the cornea. Three isoforms of TGFβ are known in mammals and the human cornea expresses all of them. TGFβ1 has been shown to play a central role in scar formation in adult corneas whereas TGFβ2 and TGFβ3 have been implicated to play a critical role in corneal development and scarless wound healing during embryogenesis. The biological effects of TGFβ in the cornea have been shown to follow SMAD dependent as well as SMAD-independent signaling pathways depending upon cellular …

Aav Serotype Influences Gene Transfer In Corneal Stroma In Vivo, Ajay Sharma, Jonathan C. K. Tovey, Arkasubhra Ghosh, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

This study evaluated the cellular tropism and relative transduction efficiency of three AAV serotypes, AAV6, AAV8 and AAV9, for corneal gene delivery using mouse cornea in vivo and donor human cornea ex vivo. The AAV6, AAV8 and AAV9 serotypes having AAV2 plasmid encoding for alkaline phosphatase (AP) gene were generated by transfecting HEK293 cell line with pHelper, pARAP4 and pRep/Cap plasmids. Viral vectors (109 vg/μl) were topically applied onto mouse cornea in vivo and human cornea ex vivo after removing the epithelium. Human corneas were processed for transgene delivery at day 5 after viral vector application. Mouse corneas were harvested …

Isolation And Cultivation Of Equine Corneal Keratocytes, Fibroblasts And Myofibroblasts, Dylan G. Buss, Elizabeth A. Giuliano, Ajay Sharma, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—To establish an in vitro model for the investigation of equine corneal wound healing. To accomplish this goal, a protocol to isolate and culture equine corneal keratocytes, fibroblasts and myofibroblasts was developed.

Animal material—Equine corneal buttons were aseptically harvested from healthy research horses undergoing humane euthanasia for reasons unrelated to this study. Slit-lamp biomicroscopy was performed prior to euthanasia by a board-certified veterinary ophthalmologist to ensure that all samples were harvested from horses free of anterior segment disease.

Procedure—Equine corneal stroma was isolated using mechanical techniques and stromal subsections were then cultured. Customized media at different culture conditions was used …

Localization Of Angiotensin Converting Enzyme In Rabbit Cornea And Its Role In Controlling Corneal Angiogenesis In Vivo, Ajay Sharma, Daniel I. Bettis, John W. Cowden, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Purpose: The renin angiotensin system (RAS) has been shown to modulate vascular endothelial growth factor and angiogenesis. In this study we investigated (i) the existence of the RAS components angiotensin converting enzyme (ACE) and angiotensin II receptors (AT1 and AT2) in the rabbit cornea using in vitro and ex vivo models and (ii) the effect of enalapril, an ACE inhibitor, to inhibit angiogenesis in rabbit cornea in vivo.

Methods: New Zealand White rabbits were used. Cultured corneal fibroblasts and corneal epithelial cells were used for RNA isolation and cDNA preparation using standard molecular biology techniques. PCR was performed to …

Efficacy And Safety Of Mitomycin C As An Agent To Treat Corneal Scarring In Horses Using An In Vitro Model, Dylan G. Buss, Ajay Sharma, Elizabeth A. Giuliano, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—Mitomycin C (MMC) is used clinically to treat corneal scarring in human patients. We investigated the safety and efficacy of MMC to treat corneal scarring in horses by examining its effects at the early and late stages of disease using an in-vitro model.

Procedure—An in-vitro model of equine corneal fibroblast (ECF) developed was used. The equine corneal fibroblast or myofibroblast cultures were produced by growing primary ECF in the presence or absence of transforming growth factor beta-1 (TGFβ1) under serum-free conditions. The MMC dose for the equine cornea was defined with dose-dependent trypan blue exclusion and MTT [(3-4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays …