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Full-Text Articles in Ophthalmology

Differential Effect Of Proinflammatory Cytokines On Corneal And Conjunctival Epithelial Cell Mucins And Glycocalyx, Kiumars Shamloo, Priya Mistry, Ashley Barbarino, Christopher Ross, Vishal Jhanji Jun 2021

Differential Effect Of Proinflammatory Cytokines On Corneal And Conjunctival Epithelial Cell Mucins And Glycocalyx, Kiumars Shamloo, Priya Mistry, Ashley Barbarino, Christopher Ross, Vishal Jhanji

Pharmacy Faculty Articles and Research

Purpose: Ocular surface mucins and glycocalyx are critical for providing ocular hydration as well lubrication and repelling pathogens or allergens. Elevated levels of tear proinflammatory cytokines in dry eye may have detrimental effect on mucins and glycocalyx. The present study tested the effect of proinflammatory cytokines IL-6, TNF-α, and IFN-γ on membrane-tethered mucins expression, glycocalyx, and viability of ocular surface epithelial cells.

Methods: Stratified cultures of human corneal and conjunctival epithelial cells were exposed to different concentrations of IL-6, TNF-α, and IFN-γ for 24 hours. The mucins gene and protein expressions were quantified by real-time polymerase chain reaction …


Resident Immune Cells Of The Avascular Lens: Mediators Of The Injury And Fibrotic Response Of The Lens., A. Menko, Jodirae Dedreu, Caitlin M. Logan, Heather Paulson, Alex V Levin, Janice L Walker Apr 2021

Resident Immune Cells Of The Avascular Lens: Mediators Of The Injury And Fibrotic Response Of The Lens., A. Menko, Jodirae Dedreu, Caitlin M. Logan, Heather Paulson, Alex V Levin, Janice L Walker

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Tissues typically harbor subpopulations of resident immune cells that function as rapid responders to injury and whose activation leads to induction of an adaptive immune response, playing important roles in repair and protection. Since the lens is an avascular tissue, it was presumed that it was absent of resident immune cells. Our studies now show that resident immune cells are a shared feature of the human, mouse, and chicken lens epithelium. These resident immune cells function as immediate responders to injury and rapidly populate the wound edge following mock cataract surgery to function as leader cells. Many of these resident …


Differential Leukocyte And Platelet Profiles In Distinct Models Of Traumatic Brain Injury, William Brad Hubbard, Meenakshi Banerjee, Hemendra J. Vekaria, Kanakanagavalli Shravani Prakhya, Smita Joshi, Qingjun Wang, Kathryn E. Saatman, Sidney W. Whiteheart, Patrick G. Sullivan Feb 2021

Differential Leukocyte And Platelet Profiles In Distinct Models Of Traumatic Brain Injury, William Brad Hubbard, Meenakshi Banerjee, Hemendra J. Vekaria, Kanakanagavalli Shravani Prakhya, Smita Joshi, Qingjun Wang, Kathryn E. Saatman, Sidney W. Whiteheart, Patrick G. Sullivan

Spinal Cord and Brain Injury Research Center Faculty Publications

Traumatic brain injury (TBI) affects over 3 million individuals every year in the U.S. There is growing appreciation that TBI can produce systemic modifications, which are in part propagated through blood–brain barrier (BBB) dysfunction and blood–brain cell interactions. As such, platelets and leukocytes contribute to mechanisms of thromboinflammation after TBI. While these mechanisms have been investigated in experimental models of contusion brain injury, less is known regarding acute alterations following mild closed head injury. To investigate the role of platelet dynamics and bioenergetics after TBI, we employed two distinct, well-established models of TBI in mice: the controlled cortical impact (CCI) …


Resident Heart Rate Variability During Cataract Surgery, Ahmad Baiyasi, Shibandri Das, Ferris Bayasi, Faisal Ridha Al-Timimi Jan 2021

Resident Heart Rate Variability During Cataract Surgery, Ahmad Baiyasi, Shibandri Das, Ferris Bayasi, Faisal Ridha Al-Timimi

Medical Student Research Symposium

Purpose: To evaluate ophthalmology resident anxiousness and cardiovascular response by tracking resident heart rate (HR) when performing cataract surgery during their last year of residency.

Methods: A prospective analysis of 31 cataract cases, completed by three residents (two females and one male), at the Kresge Eye Institute in August and September 2020 was performed. Inclusion criteria for cases included all cataract cases performed by PGY-4 residents at the Kresge Eye Institute who downloaded the Heart Graph app supported by iOS. Residents with android mobile devices were excluded from the study. Informed consent was obtained from all residents who utilized the …


Heritability Of Ocular Traits In Hispanics, Aaron T. Gomez, Gladys E. Maestre, Jesus D. Melgarejo, Vincent P. Diego, Nicholas B. Blackburn, Juan B. Yepez, Michele Petitto, Felipe A. Murati, Rosa V. Pirela, Carlos A. Chavez, Winston Lee, Lama A. Al-Aswad, Matthew P. Johnson, Joseph H. Lee, John Blangero Jan 2021

Heritability Of Ocular Traits In Hispanics, Aaron T. Gomez, Gladys E. Maestre, Jesus D. Melgarejo, Vincent P. Diego, Nicholas B. Blackburn, Juan B. Yepez, Michele Petitto, Felipe A. Murati, Rosa V. Pirela, Carlos A. Chavez, Winston Lee, Lama A. Al-Aswad, Matthew P. Johnson, Joseph H. Lee, John Blangero

MEDI 9331 Scholarly Activities Clinical Years

Purpose: The burden of glaucoma disease among Hispanics is significantly higher than in their white counterparts. It remains unclear to what extent these differences are determined by genetic factors in Hispanics. We therefore examined a highly inbred family population-based cohort in Venezuela to estimate the proportion of genetic contribution of ocular traits relevant to glaucoma disease.

Methods: A subset of 67 participants ≥40y from the Maracaibo Aging Study (MAS) with family pedigree were randomly included. The papillary retinal nerve fiber layer (RNFL) and macular thickness were measured with Spectralis Domain-OCT. Heritability analyses (h2, expressed as %) …


Extracellular Vesicles Released By Human Retinal Pigment Epithelium Mediate Increased Polarised Secretion Of Drusen Proteins In Response To Amd Stressors, Miguel Flores-Bellver, Jason Mighty, Silvia Aparicio-Domingo, Kang V. Li, Cui Shi, Jing Zhou, Hannah Cobb, Patrick Mcgrath, German Michelis, Patricia Lenhart, Ganna Bilousova, Søren Heissel, Michael J. Rudy, Christina Coughlan, Andrew E. Goodspeed, S. Patricia Becerra, Stephen Redenti, M. Valeria Canto-Soler Jan 2021

Extracellular Vesicles Released By Human Retinal Pigment Epithelium Mediate Increased Polarised Secretion Of Drusen Proteins In Response To Amd Stressors, Miguel Flores-Bellver, Jason Mighty, Silvia Aparicio-Domingo, Kang V. Li, Cui Shi, Jing Zhou, Hannah Cobb, Patrick Mcgrath, German Michelis, Patricia Lenhart, Ganna Bilousova, Søren Heissel, Michael J. Rudy, Christina Coughlan, Andrew E. Goodspeed, S. Patricia Becerra, Stephen Redenti, M. Valeria Canto-Soler

Publications and Research

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. Drusen are key contributors to the etiology of AMD and the ability to modulate drusen biogenesis could lead to therapeutic strategies to slow or halt AMD progression. The mechanisms underlying drusen biogenesis, however, remain mostly unknown. Here we demonstrate that under homeostatic conditions extracellular vesicles (EVs) secreted by retinal pigment epithelium (RPE) cells are enriched in proteins associated with mechanisms involved in AMD pathophysiology, including oxidative stress, immune response, inflammation, complement system and drusen composition. Furthermore, we provide first evidence that drusen-associated proteins are released as cargo of extracellular …


Causes Of Color Blindness: Function And Failure Of The Genes That Detect Color, Dylan Taylor Dec 2020

Causes Of Color Blindness: Function And Failure Of The Genes That Detect Color, Dylan Taylor

Senior Honors Theses

Color blindness affects nearly 10% of the entire population, with multiple types of color blindness from various genetic mutations. In the following sections, the nature of light and how the human eye perceives light will be discussed. Afterward, the major forms of color blindness and their genetic causes will be considered. Once these genetic causes have been established, the current method for diagnosing color blindness will be investigated, followed by a discussion of the current treatments available to those with color blindness. Finally, a brief discussion will address possible future work for color blindness with the hope of finding better …


Bioavailability And Spatial Distribution Of Fatty Acids In The Rat Retina After Dietary Omega-3 Supplementation, Elisa Vidal, Bokkyoo Jun, William C. Gordon, Marie Annick Maire, Lucy Martine, Stéphane Grégoire, Spiro Khoury, Stephanie Cabaret, Olivier Berdeaux, Niyazi Acar, Lionel Bretillon, Nicolas G. Bazan Oct 2020

Bioavailability And Spatial Distribution Of Fatty Acids In The Rat Retina After Dietary Omega-3 Supplementation, Elisa Vidal, Bokkyoo Jun, William C. Gordon, Marie Annick Maire, Lucy Martine, Stéphane Grégoire, Spiro Khoury, Stephanie Cabaret, Olivier Berdeaux, Niyazi Acar, Lionel Bretillon, Nicolas G. Bazan

School of Medicine Faculty Publications

Spatial changes of FAs in the retina in response to different dietary n-3 formulations have never been explored, although a diet rich in EPA and DHA is recommended to protect the retina against the effects of aging. In this study, Wistar rats were fed for 8 weeks with balanced diet including either EPA-containing phospholipids (PLs), EPA-containing TGs, DHA-containing PLs, or DHA-containing TGs. Qualitative changes in FA composition of plasma, erythrocytes, and retina were evaluated by gas chromatography-flame ionization detector. Following the different dietary intakes, changes to the quantity and spatial organization of PC and PE species in retina were determined …


Multiquantal Glutamate Release From Rod Photoreceptors, Cassandra L. Hays Aug 2020

Multiquantal Glutamate Release From Rod Photoreceptors, Cassandra L. Hays

Theses & Dissertations

Neurons communicate via Ca2+-dependent release of neurotransmitters packaged into vesicles (quanta). Some CNS neurons, especially sensory synapses, can release multiple vesicles at a time, increasing information transmission and overcoming the unreliability of a stochastic process. Ribbon-bearing neurons, including retinal photoreceptors, face the challenge of encoding sensory receptor potentials into an ever-changing train of vesicle release events. We studied release of glutamate using voltage clamp to measure anion currents activated during glutamate reuptake into presynaptic terminals (IA(glu)) of salamander and mouse rods, finding that each employ distinct mechanisms for multiquantal release. In amphibian rods, we found that …


Glut1 Deficiency: Retinal Detrimental Effects Of Gliovascular Modulation, Matt Henry, John Kitchens, Juan M. Pascual, Ramiro S. Maldonado Aug 2020

Glut1 Deficiency: Retinal Detrimental Effects Of Gliovascular Modulation, Matt Henry, John Kitchens, Juan M. Pascual, Ramiro S. Maldonado

Ophthalmology and Visual Science Faculty Publications

No abstract provided.


Melanopsin-Expressing Retinal Ganglion Cells In Control Vs. Glaucomatous Retinas, Edward Hamad Jan 2020

Melanopsin-Expressing Retinal Ganglion Cells In Control Vs. Glaucomatous Retinas, Edward Hamad

Williams Honors College, Honors Research Projects

Glaucoma is a common cause of vision loss worldwide and has a large scope of symptoms, ranging from pupillary reflex defects to sleep disorders. These issues can be explained partially by a recently found subtype of retinal ganglion cells that express melanopsin, denoted melanopsin-expressing retinal ganglion cells or mRGCs for short. These cells function primarily as photoreceptors in the non-image forming pathway, but can receive input from rods and cones. Since mRGCs play a role in the pupillary reflex and regulation of the sleep-wake cycle, I investigated if glaucoma leads to the degeneration of these cells in a mouse model …


A Topical Eye Drop Versus Intra-Meibomian Gland Injection Of Bevacizumab For Meibomian Gland Dysfunction Patients., Chitchanok Tantipat Jan 2020

A Topical Eye Drop Versus Intra-Meibomian Gland Injection Of Bevacizumab For Meibomian Gland Dysfunction Patients., Chitchanok Tantipat

Chulalongkorn University Theses and Dissertations (Chula ETD)

Purpose: To compare the efficacy and safety of topical bevacizumab eye drop versus intra-meibomian gland injection of bevacizumab when used with the standard lid hygiene in meibomian gland dysfunction (MGD) patients. Methods: 60 eyes of 30 MGD patients with lid margin telangiectasia were randomized to receive 0.05% bevacizumab eye drop or single 2.5% intra-meibomian gland bevacizumab injection plus standard lid hygiene. The primary outcomes were telangiectasia grading and the computerized lid margin neovascularized area (LMNA). The secondary outcomes were the ocular surface disease index (OSDI) score, corneal staining, meibomian gland quality, meiboscore, conjunctival redness, fluorescein break up time (FBUT), noninvasive …


Agreement Of Total Corneal Power Measured By Casia 2, Pentacam Axl, And Iolmaster 700 In Normal And Keratoconic Patients, Rusaporn Yodying Jan 2020

Agreement Of Total Corneal Power Measured By Casia 2, Pentacam Axl, And Iolmaster 700 In Normal And Keratoconic Patients, Rusaporn Yodying

Chulalongkorn University Theses and Dissertations (Chula ETD)

Purpose: To evaluate agreement of total corneal power (TCP), ocular biometry and IOL power calculation measured by CASIA 2, Pentacam AXL, and IOLMaster 700 in normal and keratoconic patients Setting: King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand Design: Prospective observational study Methods: One-hundred normal eyes and 34 keratoconic eyes were enrolled. Biometric values were measured by each device for three times by two operators to evaluate repeatability and reproducibility of TCP and other parameters. The agreement of TCP and other parameters including total corneal astigmatism, anterior keratometry, anterior corneal astigmatism, posterior keratometry, posterior corneal astigmatism, anterior chamber depth, white-to-white …


Dmbt1 Inhibition Of Pseudomonas Aeruginosa Twitching Motility Involves Its N-Glycosylation And Cannot Be Conferred By The Scavenger Receptor Cysteine-Rich Bacteria-Binding Peptide Domain., Jianfang Li, Stephanie J Wan, Matteo M E Metruccio, Sophia Ma, Kamran Nazmi, Floris J Bikker, David J. Evans, Suzanne M J Fleiszig Sep 2019

Dmbt1 Inhibition Of Pseudomonas Aeruginosa Twitching Motility Involves Its N-Glycosylation And Cannot Be Conferred By The Scavenger Receptor Cysteine-Rich Bacteria-Binding Peptide Domain., Jianfang Li, Stephanie J Wan, Matteo M E Metruccio, Sophia Ma, Kamran Nazmi, Floris J Bikker, David J. Evans, Suzanne M J Fleiszig

Faculty Publications & Research of the TUC College of Pharmacy

The scavenging capacity of glycoprotein DMBT1 helps defend mucosal epithelia against microbes. DMBT1 binding to multiple bacterial species involves its conserved Scavenger Receptor Cysteine-Rich (SRCR) domains, localized to a 16-mer consensus sequence peptide, SRCRP2. Previously, we showed that DMBT1 bound Pseudomonas aeruginosa pili, and inhibited twitching motility, a pilus-mediated movement important for virulence. Here, we determined molecular characteristics required for twitching motility inhibition. Heat-denatured DMBT1 lost capacity to inhibit twitching motility and showed reduced pili binding (~40%). Size-exclusion chromatography of Lys-C-digested native DMBT1 showed that only high-Mw fractions retained activity, suggesting involvement of the N-terminal containing repeated SRCR domains with …


Etiology And Clinical Patterns Of Uveitis At Three Ophthalmic Clinics In Tajikistan, Sayyora Yuldasheva, Saidbeg Satorov, Shekhratdzon Satorov, Vyacheslav Dushenkov Sep 2019

Etiology And Clinical Patterns Of Uveitis At Three Ophthalmic Clinics In Tajikistan, Sayyora Yuldasheva, Saidbeg Satorov, Shekhratdzon Satorov, Vyacheslav Dushenkov

Publications and Research

A prospective observational study was conducted at three ophthalmic clinics to assess the clinical patterns and etiology of uveitis in the Central Asia Republic of Tajikistan. All patients underwent physical and ophthalmologic examinations. Extensive efforts were made to determine the etiology of uveitis, including workups for Behçet's Disease (BD) and Vogt–Koyanagi–Harada (VKH) syndrome. All patients were tested for the presence of HLA-B27. Presence and/or history of tuberculosis and syphilis were ruled out. HSV, CMV, Chlamydia trachomatis and HIV antibody titers were determined by ELISA. Uveitis was diagnosed in 51 patient ages 14 to 60 were with women accounted for 60.8%. …


Is Retinal Metabolic Dysfunction At The Center Of The Pathogenesis Of Age-Related Macular Degeneration?, Thierry Léveillard, Nancy J. Philp, Florian Sennlaub Feb 2019

Is Retinal Metabolic Dysfunction At The Center Of The Pathogenesis Of Age-Related Macular Degeneration?, Thierry Léveillard, Nancy J. Philp, Florian Sennlaub

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The retinal pigment epithelium (RPE) forms the outer blood⁻retina barrier and facilitates the transepithelial transport of glucose into the outer retina via GLUT1. Glucose is metabolized in photoreceptors via the tricarboxylic acid cycle (TCA) and oxidative phosphorylation (OXPHOS) but also by aerobic glycolysis to generate glycerol for the synthesis of phospholipids for the renewal of their outer segments. Aerobic glycolysis in the photoreceptors also leads to a high rate of production of lactate which is transported out of the subretinal space to the choroidal circulation by the RPE. Lactate taken up by the RPE is converted to pyruvate and metabolized …


Hyperautofluorescent Dots Are Characteristic In Ceramide Kinase Like-Associated Retinal Degeneration., Jesse D Sengillo, Galaxy Y Cho, Maarjaliis Paavo, Winston Lee, Eugenia White, Ruben Jauregui, Janet R Sparrow, Rando Allikmets, Stephen H Tsang Jan 2019

Hyperautofluorescent Dots Are Characteristic In Ceramide Kinase Like-Associated Retinal Degeneration., Jesse D Sengillo, Galaxy Y Cho, Maarjaliis Paavo, Winston Lee, Eugenia White, Ruben Jauregui, Janet R Sparrow, Rando Allikmets, Stephen H Tsang

Reading Hospital Internal Medicine Residency

There is a lack of studies which seek to discern disease expression in patients with mutations that alter retinal ceramide metabolism, specifically in the ceramide kinase like (CERKL) gene. This cross-sectional case series reports a novel phenotypic manifestation of CERKL-associated retinopathy. Four unrelated patients with homozygous CERKL mutations underwent a complete ocular exam, spectral-domain optical coherence tomography, short-wavelength fundus autofluorescence (SW-AF), quantitative autofluorescence (qAF), and full-field electroretinogram (ffERG). Decreased visual acuity and early-onset maculopathy were present in all patients. All four patients had extensive hyperautofluorescent foci surrounding an area of central atrophy on SW-AF imaging, which has not been previously …


Deep Learning Based Topology Guaranteed Surface And Mme Segmentation Of Multiple Sclerosis Subjects From Retinal Oct, Yufan He, Aaron Carass, Yihao Liu, Bruno Jedynak, Sharon D. Solomon, Shiv Saidha, Peter A. Calabresi, Jerry L. Prince Jan 2019

Deep Learning Based Topology Guaranteed Surface And Mme Segmentation Of Multiple Sclerosis Subjects From Retinal Oct, Yufan He, Aaron Carass, Yihao Liu, Bruno Jedynak, Sharon D. Solomon, Shiv Saidha, Peter A. Calabresi, Jerry L. Prince

Mathematics and Statistics Faculty Publications and Presentations

Optical coherence tomography (OCT) is a noninvasive imaging modality that can be used to obtain depth images of the retina. Patients with multiple sclerosis (MS) have thinning retinal nerve fiber and ganglion cell layers, and approximately 5% of MS patients will develop microcystic macular edema (MME) within the retina. Segmentation of both the retinal layers and MME can provide important information to help monitor MS progression. Graph-based segmentation with machine learning preprocessing is the leading method for retinal layer segmentation, providing accurate surface delineations with the correct topological ordering. However, graph methods are time-consuming and they do not optimally incorporate …


The Tumor Microenvironment Regulates Retinoblastoma Cell Survival, Zachary K. Goldsmith Dec 2018

The Tumor Microenvironment Regulates Retinoblastoma Cell Survival, Zachary K. Goldsmith

Theses and Dissertations (ETD)

Retinoblastoma (Rb) is the most common intraocular malignancy in children comprising 4% of all pediatric tumors. Early intervention increases survival rates up to 95% in developed countries; being survival rates associated to socio-economic status. Despite the high survival rates in developed countries, preservation of the eye and vision are continuing challenges in the management of Rb. Vitreous seeds constitute the greatest challenge in treatment of Rb. The unique location of these seeds within the vitreous makes them difficult to treat. Viable seeds showed reduced proliferative capacity and metabolism. making the majority refractory to current chemotherapeutics. This prompted the development of …


The Comparison Of Spectral Domain Optical Coherence Tomography (Sd-Oct) To Histopathology In A Patient With Diffuse Macular Drusen, Harold Salmons, Ralph Eagle, Md May 2018

The Comparison Of Spectral Domain Optical Coherence Tomography (Sd-Oct) To Histopathology In A Patient With Diffuse Macular Drusen, Harold Salmons, Ralph Eagle, Md

Department of Pathology Honors Program Student Research Symposium

Background: Spectral Domain Optical Coherence Tomography (SD-OCT) has become a gold standard technique in ophthalmologic practice, and has revolutionized the diagnosis and treatment of retinal disease. As SD-OCT uses low interference interferometry and mathematical algorithms to produce detailed theoretical cross-sectional images of the retina, it is crucial to examine correlations between SD-OCT images and their corresponding histopathologic slides.

Methods: In the present study, careful correlative light microscopy was performed on the eye that was enucleated from an elderly patient who had a uveal melanoma and early agerelated macular degeneration evident clinically as soft drusen. SD-OCT was performed prior to enucleation …


Novel Combination Bmp7 And Hgf Gene Therapy Instigates Selective Myofibroblast Apoptosis And Reduces Corneal Haze In Vivo, Suneel Gupta, Michael K. Fink, Arkasubhra Ghosh, Ratnakar Tripathi, Prashant R. Sinha, Ajay Sharma, Nathan P. Hesemann, Shyam S. Chaurasia, Elizabeth A. Giuliano, Rajiv R. Mohan Feb 2018

Novel Combination Bmp7 And Hgf Gene Therapy Instigates Selective Myofibroblast Apoptosis And Reduces Corneal Haze In Vivo, Suneel Gupta, Michael K. Fink, Arkasubhra Ghosh, Ratnakar Tripathi, Prashant R. Sinha, Ajay Sharma, Nathan P. Hesemann, Shyam S. Chaurasia, Elizabeth A. Giuliano, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE. We tested the potential of bone morphogenic protein 7 (BMP7) and hepatocyte growth factor (HGF) combination gene therapy to treat preformed corneal fibrosis using established rabbit in vivo and human in vitro models.

METHODS. Eighteen New Zealand White rabbits were used. Corneal fibrosis was produced by alkali injury. Twenty-four hours after scar formation, cornea received topically either balanced salt solution (BSS; n ¼ 6), polyethylenimine-conjugated gold nanoparticle (PEI2-GNP)-naked plasmid (n ¼ 6) or PEI2-GNP plasmids expressing BMP7 and HGF genes (n ¼ 6). Donor human corneas were used to obtain primary human corneal fibroblasts and myofibroblasts for mechanistic studies. …


Cone Phosphodiesterase-6Γ’ Subunit Augments Cone Pde6 Holoenzyme Assembly And Stability In A Mouse Model Lacking Both Rod And Cone Pde6 Catalytic Subunits, Wen-Tao Deng, Saravanan Kolandaivelu, Astra Dinculescu, Jie Li, Ping Zhu, Vince A. Chiodo, Visvanathan Ramamurthy, William W. Hauswirth Jan 2018

Cone Phosphodiesterase-6Γ’ Subunit Augments Cone Pde6 Holoenzyme Assembly And Stability In A Mouse Model Lacking Both Rod And Cone Pde6 Catalytic Subunits, Wen-Tao Deng, Saravanan Kolandaivelu, Astra Dinculescu, Jie Li, Ping Zhu, Vince A. Chiodo, Visvanathan Ramamurthy, William W. Hauswirth

Faculty & Staff Scholarship

Rod and cone phosphodiesterase 6 (PDE6) are key effector enzymes of the vertebrate phototransduction pathway. Rod PDE6 consists of two catalytic subunits PDE6α and PDE6β and two identical inhibitory PDE6γ subunits, while cone PDE6 is composed of two identical PDE6α’ catalytic subunits and two identical cone-specific PDE6γ’ inhibitory subunits. Despite their prominent function in regulating cGMP levels and therefore rod and cone light response properties, it is not known how each subunit contributes to the functional differences between rods and cones. In this study, we generated an rd10/cpfl1 mouse model lacking rod PDE6β and cone PDE6α’ subunits. Both rod and …


Inhibiting The Interaction Between Grp94 And Myocilin To Treat Primary Open-Angle Glaucoma, Andrew Stothert Jun 2016

Inhibiting The Interaction Between Grp94 And Myocilin To Treat Primary Open-Angle Glaucoma, Andrew Stothert

USF Tampa Graduate Theses and Dissertations

Glaucoma is a neurodegenerative protein misfolding disorder classified by increases in IOP, damage to retinal ganglion cells (RGCs), optic nerve (ON) head damage, and progressive irreversible blindness. Primary open-angle glaucoma (POAG) is the most common form of glaucoma, constituting over 90% of clinical cases. POAG is observed in patients where normal outflow channels, mainly the trabecular meshwork (TM), are exposed at the angle formed by the iris and cornea. However, due to TM cellular dysfunction, aqueous outflow resistance is increased preventing normal circulation of aqueous humor. Recent studies have shown that in 2-4% of POAG cases, increased intracellular levels of …


Characterization Of Inhibitor Of Differentiation (Id) Proteins In Human Cornea, Rajiv R. Mohan, Brandie R. Morgan, Govinduraj Anumanthan, Ajay Sharma, Shyam S. Chaurasia, Frank G. Rieger Jan 2016

Characterization Of Inhibitor Of Differentiation (Id) Proteins In Human Cornea, Rajiv R. Mohan, Brandie R. Morgan, Govinduraj Anumanthan, Ajay Sharma, Shyam S. Chaurasia, Frank G. Rieger

Pharmacy Faculty Articles and Research

Inhibitor of differentiation (Id) proteins are DNA-binding transcription factors involved in cellular proliferation, migration, inflammation, angiogenesis and fibrosis. However, their expression and role in the cornea is unknown. The present study was undertaken to characterize the expression of Id proteins and their interactions with the pro-fibrotic cytokine Transforming Growth Factor β1 (TGFβ1) and anti-fibrotic cytokine, bone morphogenic protein 7 (BMP7) in human cornea. Human donor corneas procured from Eye Bank were used. Id proteins were localized in human corneal sections using immunofluorescence. Primary cultures of human corneal fibroblasts (HCF) were established and treated with either TGFβ1 (5 ng/ml) or BMP7 …


Voxel Based Morphometry In Optical Coherence Tomography: Validation & Core Findings, Bhavna J. Antony, Min Chen, Aaron Carass, Bruno M. Jedynak, Omar Al-Louzi, Sharon D. Solomon, Shiv Saidha, Peter Calabresi, Jerry L. Prince Jan 2016

Voxel Based Morphometry In Optical Coherence Tomography: Validation & Core Findings, Bhavna J. Antony, Min Chen, Aaron Carass, Bruno M. Jedynak, Omar Al-Louzi, Sharon D. Solomon, Shiv Saidha, Peter Calabresi, Jerry L. Prince

Mathematics and Statistics Faculty Publications and Presentations

Optical coherence tomography (OCT) of the human retina is now becoming established as an important modality for the detection and tracking of various ocular diseases. Voxel based morphometry (VBM) is a long standing neuroimaging analysis technique that allows for the exploration of the regional differences in the brain. There has been limited work done in developing registration based methods for OCT, which has hampered the advancement of VBM analyses in OCT based population studies. Following on from our recent development of an OCT registration method, we explore the potential benefits of VBM analysis in cohorts of healthy controls (HCs) and …


Molecular Mechanisms Of Suberoylanilide Hydroxamic Acid In The Inhibition Of Tgf-Β1-Mediated Canine Corneal Fibrosis, Kristina M. Gronkiewicz, Elizabeth A. Giuliano, Ajay Sharma, Rajiv R. Mohan Jan 2016

Molecular Mechanisms Of Suberoylanilide Hydroxamic Acid In The Inhibition Of Tgf-Β1-Mediated Canine Corneal Fibrosis, Kristina M. Gronkiewicz, Elizabeth A. Giuliano, Ajay Sharma, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—To investigate molecular mechanisms mediating anti-fibrotic effect of SAHA in the canine cornea using an in vitro model. We hypothesized that SAHA attenuates corneal fibrosis by modulating Smad-dependent and, to a lesser extent, Smad-independent signaling pathways activated by TGF-β1, as well as matrix metalloproteinase (MMP) activity.

Methods—Cultured canine corneal fibroblasts (CCF) were incubated in the presence/absence of TGF-β1 (5ng/ml) and SAHA (2.5μM) for 24hrs. Western blot analysis was used to quantify non-phosphorylated and phosphorylated isoforms of Smad2/3, p38 MAP kinase (MAPK), ERK1/2 and JNK1. Real-time PCR and zymography were utilized to quantify MMP1, MMP2, MMP8 and MMP9 mRNA expression and …


Development Of A Novel In Vivo Corneal Fibrosis Model In The Dog, K. M. Gronkiewicz, Elizabeth A. Giuliano, K. Kuroki, F. Bunyak, Ajay Sharma, L. B. C. Teixeira, C. W. Hamm, R. R. Mohan Jan 2016

Development Of A Novel In Vivo Corneal Fibrosis Model In The Dog, K. M. Gronkiewicz, Elizabeth A. Giuliano, K. Kuroki, F. Bunyak, Ajay Sharma, L. B. C. Teixeira, C. W. Hamm, R. R. Mohan

Pharmacy Faculty Articles and Research

The aim of this study was to develop a novel in vivo corneal model of fibrosis in dogs utilizing alkali burn and determine the ability of suberanilohydroxamic acid (SAHA) to inhibit corneal fibrosis using this large animal model. To accomplish this, we used seven research Beagle dogs. An axial corneal alkali burn in dogs was created using 1 N NaOH topically. Six dogs were randomly and equally assigned into 2 groups: A) vehicle (DMSO, 2 μL/mL); B) anti-fibrotic treatment (50 μM SAHA). The degree of corneal opacity, ocular health, and anti-fibrotic effects of SAHA were determined utilizing the Fantes grading …


Epigenetic Modification Prevents Excessive Wound Healing And Scar Formation After Glaucoma Filtration Surgery, Ajay Sharma, Govindaraj Anumanthan, Marcos Reyes, Huiyi Chen, Jason W. Brubaker, Saad Siddiqui, Suneel Gupta, Frank G. Rieger, Rajiv R. Mohan Jan 2016

Epigenetic Modification Prevents Excessive Wound Healing And Scar Formation After Glaucoma Filtration Surgery, Ajay Sharma, Govindaraj Anumanthan, Marcos Reyes, Huiyi Chen, Jason W. Brubaker, Saad Siddiqui, Suneel Gupta, Frank G. Rieger, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE. The purpose of this study was to determine the efficacy of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor (HDACi), in prevention of excessive wound healing and scar formation in a rabbit model of glaucoma filtration surgery (GFS).

METHODS. A rabbit model of GFS was used. Rabbits that underwent GFS received balanced salt solution, or SAHA (50 lM), or mitomycin C (0.02%). Clinical scores of IOP, bleb vascularity, and slit-lamp examination were performed. On postoperative day 14, rabbits were killed and the bleb tissues were collected for evaluation of tissue fibrosis with hematoxylin and eosin, Masson trichrome, a-smooth muscle …


Role Of 5'Tg3'-Interacting Factors (Tgifs) In Vorinostat (Hdac Inhibitor)-Mediated Corneal Fibrosis Inhibition, Ajay Sharma, Nishant R. Sinha, Saad Siddiqui, Rajiv R. Mohan Jan 2015

Role Of 5'Tg3'-Interacting Factors (Tgifs) In Vorinostat (Hdac Inhibitor)-Mediated Corneal Fibrosis Inhibition, Ajay Sharma, Nishant R. Sinha, Saad Siddiqui, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Purpose: We have previously reported that vorinostat, an FDA-approved, clinically used histone deacetylase (HDAC) inhibitor, attenuates corneal fibrosis in vivo in rabbits by blocking transforming growth factor β (TGFβ). The 5′TG3′-interacting factors (TGIFs) are transcriptional repressors of TGFβ1 signaling via the Smad pathway. The present study was designed to explore the expression of TGIFs in human corneal fibroblasts and to investigate their role in mediating the antifibrotic effect of vorinostat.

Methods: Human corneal fibroblast cultures were generated from donor corneas. RNA isolation, cDNA preparation, and PCR were performed to detect the presence of TGIF1 and TGIF2 transcripts. The cultures were …


Differential Eye Movements In Mild Traumatic Brain Injury Vs. Normal Controls, Joanna R. Wares, David X. Cifu, Kathy W. Hoke, Paul A. Wetzel, George Gitchel, William Carne Jan 2014

Differential Eye Movements In Mild Traumatic Brain Injury Vs. Normal Controls, Joanna R. Wares, David X. Cifu, Kathy W. Hoke, Paul A. Wetzel, George Gitchel, William Carne

Department of Math & Statistics Faculty Publications

Objective measures to diagnose and to monitor improvement of symptoms following mild traumatic brain injury (mTBI) are lacking. Computerized eye tracking has been advocated as a rapid, user friendly and field ready technique to meet this need. Eye tracking data collected via a head mounted, video-based binocular eye tracker was used to examine saccades, fixations and smooth pursuit movement in 60 military Service Members with post concussive syndrome (PCS) and 26 asymptomatic control subjects in an effort to determine if eye movement differences could be found and quantified. The diagnosis of mTBI was confirmed by the study physiatrist’s history, physical …