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Retinoblastoma Tells The Story Of Our Health Care System, Irshad Soomro, Muhammad Nadeem Khan, Suhail Muzaffar, Naila Kayani, Shahid Pervez, Akbar Shah Hussainy, Rashida Ahmed, Sheema H. Hasan 2017 Aga Khan University

Retinoblastoma Tells The Story Of Our Health Care System, Irshad Soomro, Muhammad Nadeem Khan, Suhail Muzaffar, Naila Kayani, Shahid Pervez, Akbar Shah Hussainy, Rashida Ahmed, Sheema H. Hasan

Rashida Ahmed

Objective: To review cases of retinoblastoma. Setting: Department of Pathology Aga Khan University Hospital Karachi. Method: Twenty three specimens from cases of retinoblastoma received over a period of eight years were routinely processes and stained with haematoxylin and Eosin stain Other stains were used for tuberculosis and melanin. Immunochemistry was resorted to in undifferentiated tumors. Results: Over 60% cases of retinoblastoma were diagnosed after 5 years and nine cases showed involvement of opti-nerve. Conclusion: Late diagnosis of retinoblastoma effects the stage of the tumors and the prognisis.


Atorvastatin Promotes Phagocytosis And Attenuates Pro-Inflammatory Response In Human Retinal Pigment Epithelial Cells, Bo Tian, Ahmad Al-Moujahed, Peggy Bouzika, Yijun Hu, Shoji Notomi, Pavlina Tsoka, Joan W. Miller, Haijiang Lin, Demetrios G. Vavvas 2017 Harvard Medical School

Atorvastatin Promotes Phagocytosis And Attenuates Pro-Inflammatory Response In Human Retinal Pigment Epithelial Cells, Bo Tian, Ahmad Al-Moujahed, Peggy Bouzika, Yijun Hu, Shoji Notomi, Pavlina Tsoka, Joan W. Miller, Haijiang Lin, Demetrios G. Vavvas

Open Access Articles

Phagocytosis of daily shed photoreceptor outer segments is an important function of the retinal pigment epithelium (RPE) and it is essential for retinal homeostasis. RPE dysfunction, especially impairment of its phagocytic ability, plays an essential role in the pathogenesis of age-related macular degeneration (AMD). Statins, or HMG CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors, are drugs with multiple properties that have been extensively used to treat hyperlipidemia. However, their effect on RPE cells has not been fully elucidated. Here we report that high dose atorvastatin increased the phagocytic function of ARPE-19 cells, as well as rescue the cells from the phagocytic dysfunction ...


Interaction Of The Tear Film With The Ocular Surface, Richard J. Braun, Amy Janett, Nicholas Gewecke, Spencer Walker 2017 University of Delaware

Interaction Of The Tear Film With The Ocular Surface, Richard J. Braun, Amy Janett, Nicholas Gewecke, Spencer Walker

Biology and Medicine Through Mathematics Conference

No abstract provided.


Quantitative Microvascular Analysis Of Retinal Venous Occlusions By Spectral Domain Optical Coherence Tomography Angiography, Nicole Koulisis, Alice Y. Kim, Zhongdi Chu, Anoush Shahidzadeh, Bruce Burkemper, Lisa C. Olmos de Koo, Andrew A. Moshfeghi, Hossein Ameri, Carmen A. Puliafito, Veronica L. Isozaki, Ruikang K. Wang, Amir H. Kashani 2017 University of Massachusetts Medical School

Quantitative Microvascular Analysis Of Retinal Venous Occlusions By Spectral Domain Optical Coherence Tomography Angiography, Nicole Koulisis, Alice Y. Kim, Zhongdi Chu, Anoush Shahidzadeh, Bruce Burkemper, Lisa C. Olmos De Koo, Andrew A. Moshfeghi, Hossein Ameri, Carmen A. Puliafito, Veronica L. Isozaki, Ruikang K. Wang, Amir H. Kashani

Open Access Articles

PURPOSE: To quantitatively evaluate the retinal microvasculature in human subjects with retinal venous occlusions (RVO) using optical coherence tomography angiography (OCTA). DESIGN: Retrospective, cross-sectional, observational case series. PARTICIPANTS: Sixty subjects (84 eyes) were included (20 BRVO, 14 CRVO, 24 unaffected fellow eyes, and 26 controls). METHODS: OCTA was performed on a prototype, spectral domain-OCTA system in the 3x3mm central macular region. Custom software was used to quantify morphology and density of retinal capillaries using four quantitative parameters. The vasculature of the segmented retinal layers and nonsegmented whole retina were analyzed. MAIN OUTCOME MEASURES: Fractal dimension (FD), vessel density (VD), skeletal ...


Latanoprost And Timolol In Hydrogel Soft Drug-Dispensing Contact Lenses: A Comparative Analysis, Neha Potdar 2017 Virginia Commonwealth University

Latanoprost And Timolol In Hydrogel Soft Drug-Dispensing Contact Lenses: A Comparative Analysis, Neha Potdar

Virginias Collegiate Honors Council Conference

Glaucoma patients only can instill glaucoma eye drops. This results in 1-7% absorption of the medication. Surveys show that patients forget to take their medication and have difficulty inserting their eye drops. Researchers at the Massachusetts Eye and Ear Infirmary have developed latanoprost drug-dispensing hydrogel soft contact lenses that dispense the drug to help facilitate the process. However, some glaucoma patients do not respond to latanoprost because they have uveitic glaucoma or do not want to experience latanoprost’s ocular side effects. Patients need an alternative which can be inserted into these contact lenses. Another commonly used glaucoma drug is ...


Inhibition Or Stimulation Of Autophagy Affects Early Formation Of Lipofuscin-Like Autofluorescence In The Retinal Pigment Epithelium Cell, Lei Lei, Radouil T. Tzekov, Huapeng Li, J. Hugh McDowell, Guangping Gao, W. Clay Smith, Shibo Tang, Shalesh Kaushal 2017 Sun Yat-sen University, China

Inhibition Or Stimulation Of Autophagy Affects Early Formation Of Lipofuscin-Like Autofluorescence In The Retinal Pigment Epithelium Cell, Lei Lei, Radouil T. Tzekov, Huapeng Li, J. Hugh Mcdowell, Guangping Gao, W. Clay Smith, Shibo Tang, Shalesh Kaushal

Open Access Articles

The accumulation of lipofuscin in the retinal pigment epithelium (RPE) is dependent on the effectiveness of photoreceptor outer segment material degradation. This study explored the role of autophagy in the fate of RPE lipofuscin degradation. After seven days of feeding with either native or modified rod outer segments, ARPE-19 cells were treated with enhancers or inhibitors of autophagy and the autofluorescence was detected by fluorescence-activated cell sorting. Supplementation with different types of rod outer segments increased lipofuscin-like autofluorescence (LLAF) after the inhibition of autophagy, while the induction of autophagy (e.g., application of rapamycin) decreased LLAF. The effects of autophagy ...


Antibiotic Prophylaxis In Orbital Fractures., Benjamin Reiss, Lamise Rajjoub, Tamer Mansour, Tony Chen, Aisha Mumtaz 2017 George Washington University

Antibiotic Prophylaxis In Orbital Fractures., Benjamin Reiss, Lamise Rajjoub, Tamer Mansour, Tony Chen, Aisha Mumtaz

Ophthalmology Faculty Publications

Purpose:

To determine whether prophylactic antibiotic use in patients with orbital fracture prevent orbital infection.

Design:

Retrospective cohort study.

Participants:

All patients diagnosed with orbital fracture between January 1, 2008 and March 1, 2014 at The George Washington University Hospital and Clinics.

Main Outcome Measures:

Development of orbital infection.

Results:

One hundred seventy-two patients with orbital fracture met our inclusion and exclusion criteria. No orbital infections were documented. Twenty subjects (12%) received no prophylactic antibiotic, and two (1%) received only one dose of antibiotics pre-operatively for surgery. For primary antibiotic, 136 subjects (79%) received oral antibiotics, and 14 (8%) received ...


Why Is There An Association Between Retinal Vein Occlusion, Vision Loss, Myocardial Infarction, Stroke And Mortality: Potential Roles Of Hypomagnesaemia, Release Of Sphingolipids, And Platelet-Activating Factor, Burton M. Altura, Asefa Gebrewold, Nilank C. Shah, Aimin Zhang, Wenyan Li, Lawrence M. Resnick, Bella T. Altura 2017 Touro College of Osteopathic Medicine (Middletown)

Why Is There An Association Between Retinal Vein Occlusion, Vision Loss, Myocardial Infarction, Stroke And Mortality: Potential Roles Of Hypomagnesaemia, Release Of Sphingolipids, And Platelet-Activating Factor, Burton M. Altura, Asefa Gebrewold, Nilank C. Shah, Aimin Zhang, Wenyan Li, Lawrence M. Resnick, Bella T. Altura

Touro College of Osteopathic Medicine (Middletown) Publications and Research

Although numerous hypotheses (and potential risk factors), have been offered to explain the origins and potential mechanism(s) for central retinal vein occlusion (RVO) in patients of diverse ages, there is no agreement. Recently, considerable epidemiological evidence has been brought forth which indicates a strong association between RVO, myocardial infarctions, heart failure, and stroke. Magnesium (Mg) deficiency (mgD) has long-been associated with glaucoma and diabetic retinopathy. Over the past three decades, our laboratories have found strong associations of mgD linked to morbidity/ mortality in cardiovascular diseases such as myocardial infarctions, cardiac failure, atherogenesis, and strokes, both experimentally and clinically. More ...


Is Stem Cell Transplantation A Practical Treatment For Macular Degeneration?, Zachary Slepchuk 2017 Assumption College

Is Stem Cell Transplantation A Practical Treatment For Macular Degeneration?, Zachary Slepchuk

Honors Theses

No abstract provided.


Macular Pigment Is Associated With Glare-Affected Visual Function And Central Visual Field Loss In Glaucoma, James Loughman, We Fong Siah, Colm O’Brien 2017 Dublin Institute of Technology

Macular Pigment Is Associated With Glare-Affected Visual Function And Central Visual Field Loss In Glaucoma, James Loughman, We Fong Siah, Colm O’Brien

Articles

Aim

To evaluate the relationship between macular pigment optical density (MPOD) and glare disability in open-angle glaucoma.

Methods A cross-sectional analysis of baseline data (88 subjects; median age, 67 (range 36–84) years) collected during the Macular Pigment and Glaucoma Trial (ISRCTN registry number: 56985060). MPOD at 0.25°, 0.5° and 1° of retinal eccentricity was measured using customised heterochromatic flicker photometry. Mesopic contrast sensitivity with glare (mCSg), photostress recovery time (PRT) and self-reported glare symptoms were evaluated. Fourier-domain optical coherence tomography was used to analyse ganglion cell complex (GCC) and identify foveal involvement.

Results Low spatial frequency (f ...


A Sema3c Mutant Resistant To Cleavage By Furin (Fr-Sema3c) Inhibits Choroidal Neovascularization, Shira Toledano, Huayi Lu, Agustina Palacio, Keren Ziv, Ofra Kessler, Shlomit Schaal, Gera Neufeld, Yoreh Barak 2016 Cancer Research and Vascular Biology Center

A Sema3c Mutant Resistant To Cleavage By Furin (Fr-Sema3c) Inhibits Choroidal Neovascularization, Shira Toledano, Huayi Lu, Agustina Palacio, Keren Ziv, Ofra Kessler, Shlomit Schaal, Gera Neufeld, Yoreh Barak

Open Access Articles

In age-related macular degeneration (AMD), abnormal sub retinal choroidal neovascularization (CNV) is a major cause of blindness. FR-sema3C is a point mutated form of semaphorin-3C that is resistant to cleavage by furin like pro-protein convertases (FPPC). We have found in previous work that FR-sema3C functions as an anti-angiogenic factor. In this study we investigated the possible use of FR-sema3C as an inhibitor of CNV. FR-sema3C inhibits VEGF as well as PDGF-BB signal transduction in endothelial cells and to less extent bFGF induced signal transduction using a mechanism that does not depend upon the binding of VEGF like the drugs that ...


Cost-Effectiveness Of Selective Laser Trabeculoplasty (Slt) Versus Argon Laser Trabeculoplasty (Alt) In Uncontrolled Open Angle Glaucoma Patients Having At Least One Full Previous Slt: An Economic Evaluation Alongside An Ongoing Randomized Controlled Clinical Trial, Muhammad Rakibuz-Zaman 2016 The University of Western Ontario

Cost-Effectiveness Of Selective Laser Trabeculoplasty (Slt) Versus Argon Laser Trabeculoplasty (Alt) In Uncontrolled Open Angle Glaucoma Patients Having At Least One Full Previous Slt: An Economic Evaluation Alongside An Ongoing Randomized Controlled Clinical Trial, Muhammad Rakibuz-Zaman

Electronic Thesis and Dissertation Repository

Background and objective: ALT and SLT are both safe and effective for glaucoma treatment. We performed a cost-effectiveness analysis (CEA) of SLT versus ALT for a six-month follow-up period in uncontrolled open angle glaucoma patients having at least one full previous SLT from an ongoing RCT. Methods: Trial based treatment costing and IOP reduction at 6-month follow-up from baseline for both intervention arms were calculated. A decision tree model was developed considering possible clinical pathways of patients undergoing repeat laser trabeculoplasty. CEA among ALT and SLT was done, and ICERs were calculated from both societal and ministry perspective. One way ...


Impact Of Microbiota On Resistance To Ocular Pseudomonas Aeruginosa-Induced Keratitis, Abirami Kugadas, Stig Hill Christiansen, Saiprasad Sankaranarayanan, Neeraj K. Surana, Stefanie Gauguet, Ryan Kunz, Raina Fichorova, Thomas Vorup-Jensen, Mihaela Gadjeva 2016 Harvard Medical School

Impact Of Microbiota On Resistance To Ocular Pseudomonas Aeruginosa-Induced Keratitis, Abirami Kugadas, Stig Hill Christiansen, Saiprasad Sankaranarayanan, Neeraj K. Surana, Stefanie Gauguet, Ryan Kunz, Raina Fichorova, Thomas Vorup-Jensen, Mihaela Gadjeva

Pediatric Publications and Presentations

The existence of the ocular microbiota has been reported but functional analyses to evaluate its significance in regulating ocular immunity are currently lacking. We compared the relative contribution of eye and gut commensals in regulating the ocular susceptibility to Pseudomonas aeruginosa-induced keratitis. We find that in health, the presence of microbiota strengthened the ocular innate immune barrier by significantly increasing the concentrations of immune effectors in the tear film, including secretory IgA and complement proteins. Consistent with this view, Swiss Webster (SW) mice that are typically resistant to P. aeruginosa-induced keratitis become susceptible due to the lack of microbiota. This ...


Advances In Gene Therapy For Diseases Of The Eye, Lolita Petit, Hemant Khanna, Claudio Punzo 2016 University of Massachusetts Medical School

Advances In Gene Therapy For Diseases Of The Eye, Lolita Petit, Hemant Khanna, Claudio Punzo

UMass Metabolic Network Publications

Over the last few years, huge progress has been made with regard to the understanding of molecular mechanisms underlying the pathogenesis of neurodegenerative diseases of the eye. Such knowledge has led to the development of gene therapy approaches to treat these devastating disorders. Challenges regarding the efficacy and efficiency of therapeutic gene delivery have driven the development of novel therapeutic approaches, which continue to evolve the field of ocular gene therapy. In this review article, we will discuss the evolution of preclinical and clinical strategies that have improved gene therapy in the eye, showing that treatment of vision loss has ...


Results At 2 Years After Gene Therapy For Rpe65-Deficient Leber Congenital Amaurosis And Severe Early-Childhood-Onset Retinal Dystrophy, Richard G. Weleber, Mark E. Pennesi, David J. Wilson, Shalesh Kaushal, Laura R. Erker, Lauren Jensen, Maureen T. McBride, Terence R. Flotte, Margaret Humphries, Roberto Calcedo, William W. Hauswirth, Jeffrey D. Chulay, J. Timothy Stout 2016 Oregon Health & Science University

Results At 2 Years After Gene Therapy For Rpe65-Deficient Leber Congenital Amaurosis And Severe Early-Childhood-Onset Retinal Dystrophy, Richard G. Weleber, Mark E. Pennesi, David J. Wilson, Shalesh Kaushal, Laura R. Erker, Lauren Jensen, Maureen T. Mcbride, Terence R. Flotte, Margaret Humphries, Roberto Calcedo, William W. Hauswirth, Jeffrey D. Chulay, J. Timothy Stout

Open Access Articles

PURPOSE: To provide an initial assessment of the safety of a recombinant adeno-associated virus vector expressing RPE65 (rAAV2-CB-hRPE65) in adults and children with retinal degeneration caused by RPE65 mutations.

DESIGN: Nonrandomized, multicenter clinical trial.

PARTICIPANTS: Eight adults and 4 children, 6 to 39 years of age, with Leber congenital amaurosis (LCA) or severe early-childhood-onset retinal degeneration (SECORD).

METHODS: Patients received a subretinal injection of rAAV2-CB-hRPE65 in the poorer-seeing eye, at either of 2 dose levels, and were followed up for 2 years after treatment.

MAIN OUTCOME MEASURES: The primary safety measures were ocular and nonocular adverse events. Exploratory efficacy measures ...


Prenylated Retinal Ciliopathy Protein Rpgr Regulates Ciliary Localization Of Joubert Syndrome-Associated Protein Inpp5e In Cooperation With Pde6, Wei Zhang, Kollu N. Rao, Linjing Li, Manisha Anand, Hemant Khanna 2016 University of Massachusetts Medical School

Prenylated Retinal Ciliopathy Protein Rpgr Regulates Ciliary Localization Of Joubert Syndrome-Associated Protein Inpp5e In Cooperation With Pde6, Wei Zhang, Kollu N. Rao, Linjing Li, Manisha Anand, Hemant Khanna

UMass Center for Clinical and Translational Science Research Retreat

Ciliary dysfunction is an underlying cause of severe human disorders (collectively called ciliopathies), such as retinitis pigmentosa (RP), Joubert Syndrome (JBTS), and Bardet-Biedl Syndrome. Ciliary proteins form distinct functional networks for localization to cilia as well as regulation of ciliary function. However, not much is known about the mechanism of ciliary localization and function of RPGR (retinitis pigmentosa GTPase regulator), a ciliary protein frequently associated with RP worldwide. Using tandem mass spectrometry analysis, we show that RPGR interacts with two JBTS-associated proteins: PDE6Π (delta subunit of Phosphodiesterase; a prenyl-binding protein) and INPP5E (inositol polyphosphate-5-phosphatase 5E; a ciliary cargo). Whereas PDE6Π ...


The Carboxyl Terminal Mutational Hotspot Of The Ciliary Disease Protein Rpgrorf15 (Retinitis Pigmentosa Gtpase Regulator) Is Glutamylated In Vivo, Kollu N. Rao, Manisha Anand, Hemant Khanna 2016 University of Massachusetts Medical School

The Carboxyl Terminal Mutational Hotspot Of The Ciliary Disease Protein Rpgrorf15 (Retinitis Pigmentosa Gtpase Regulator) Is Glutamylated In Vivo, Kollu N. Rao, Manisha Anand, Hemant Khanna

Open Access Articles

Mutations inRPGR(ORF15)(retinitis pigmentosa GTPase regulator) are a major cause of inherited retinal degenerative diseases. RPGR(ORF15)(1152 residues) is a ciliary protein involved in regulating the composition and function of photoreceptor cilia. The mutational hotspot in RPGR(ORF15)is an unusual C-terminal domain encoded by exon ORF15, which is rich in polyglutamates and glycine residues (Glu-Gly domain) followed by a short stretch of basic amino acid residues (RPGR(C2)domain; residues 1072-1152). However, the properties of the ORF15-encoded domain and its involvement in the pathogenesis of the disease are unclear. Here we show that RPGR(ORF15)is glutamylated ...


Activation Of Mtorc1 Improves Cone Cell Metabolism And Extends Vision In Retinitis Pigmentosa Mice: A Dissertation, Aditya Venkatesh 2016 University of Massachusetts Medical School

Activation Of Mtorc1 Improves Cone Cell Metabolism And Extends Vision In Retinitis Pigmentosa Mice: A Dissertation, Aditya Venkatesh

GSBS Dissertations and Theses

Retinitis Pigmentosa (RP) is an inherited photoreceptor degenerative disease that leads to blindness and affects about 1 in 4000 people worldwide. The disease is predominantly caused by mutations in genes expressed exclusively in the night active rod photoreceptors; however, blindness results from the secondary loss of the day active cone photoreceptors, the mechanism of which remains elusive. Here, we show that the mammalian target of rapamycin complex 1 (mTORC1) is required to delay the progression of cone death during disease and that constitutive activation of mTORC1 is sufficient to maintain cone function and promote cone survival in RP. Activation of ...


Microrna-34a-Mediated Down-Regulation Of The Microglial-Enriched Triggering Receptor And Phagocytosis-Sensor Trem2 In Age-Related Macular Degeneration, Surjyadipta Bhattacharjee, Yuhai Zhao, Prerna Dua, Evgeny I. Rogaev, Walter J. Lukiw 2016 Louisiana State University Health Science Center

Microrna-34a-Mediated Down-Regulation Of The Microglial-Enriched Triggering Receptor And Phagocytosis-Sensor Trem2 In Age-Related Macular Degeneration, Surjyadipta Bhattacharjee, Yuhai Zhao, Prerna Dua, Evgeny I. Rogaev, Walter J. Lukiw

Psychiatry Publications and Presentations

The aggregation of Abeta42-peptides and the formation of drusen in age-related macular degeneration (AMD) are due in part to the inability of homeostatic phagocytic mechanisms to clear self-aggregating Abeta42-peptides from the extracellular space. The triggering receptor expressed in myeloid/microglial cells-2 (TREM2), a trans-membrane-spanning, sensor-receptor of the immune-globulin/lectin-like gene superfamily is a critical component of Abeta42-peptide clearance. Here we report a significant deficit in TREM2 in AMD retina and in cytokine- or oxidatively-stressed microglial (MG) cells. RT-PCR, miRNA-array, LED-Northern and Western blot studies indicated up-regulation of a microglial-enriched NF-small ka, CyrillicB-sensitive miRNA-34a coupled to a down-regulation of TREM2 in ...


Improved Cell Metabolism Prolongs Photoreceptor Survival Upon Retinal-Pigmented Epithelium Loss In The Sodium Iodate Induced Model Of Geographic Atrophy, Marina Zieger, Claudio Punzo 2016 University of Massachusetts Medical School

Improved Cell Metabolism Prolongs Photoreceptor Survival Upon Retinal-Pigmented Epithelium Loss In The Sodium Iodate Induced Model Of Geographic Atrophy, Marina Zieger, Claudio Punzo

Open Access Articles

Age-related macular degeneration (AMD) is characterized by malfunction and loss of retinal-pigmented epithelium (RPE) cells. Because the RPE transfers nutrients from the choriocapillaris to photoreceptor (PR), PRs are affected as well. Geographic atrophy (GA) is an advanced form of AMD characterized by severe vision impairment due to RPE loss over large areas. Currently there is no treatment to delay the degeneration of nutrient deprived PRs once RPE cells die. Here we show that cell-autonomous activation of the key regulator of cell metabolism, the kinase mammalian target of rapamycin complex 1 (mTORC1), delays PR death in the sodium iodate induced model ...


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