Ophthalmology Commons^™

Mutations In Arl2bp, A Protein Required For Ciliary Microtubule Structure, Cause Syndromic Male Infertility In Humans And Mice, Abigal R. Moye, Nicola Bedoni, Jessica G. Cunningham, Urikhan Sanzhaeva, Eric S. Tucker, Peter Mathers, Virginie G. Peter, Mathieu Quinodoz, Liliana P. Paris, Luisa Coutinho-Santos, Pedro Camacho, Madeleine G. Purcell, Abbie C. Winkelmann, James A. Foster, Elena N. Pugacheva, Carlo Rivolta, Visvanathan Ramamurthy

Faculty & Staff Scholarship

Cilia are evolutionarily conserved hair-like structures with a wide spectrum of key biological roles, and their dysfunction has been linked to a growing class of genetic disorders, known collectively as ciliopathies. Many strides have been made towards deciphering the molecular causes for these diseases, which have in turn expanded the understanding of cilia and their functional roles. One recently-identified ciliary gene is ARL2BP, encoding the ADP-Ribosylation Factor Like 2 Binding Protein. In this study, we have identified multiple ciliopathy phenotypes associated with mutations in ARL2BP in human patients and in a mouse knockout model. Our research demonstrates that spermiogenesis …

Human Macular Müller Cells Rely More On Serine Biosynthesis To Combat Oxidative Stress Than Those From The Periphery, Ting Zhang, Ling Zhu, Michele C. Madigan, Wei Liu, Weiyong Shen, Svetlana Cherepanoff, Fanfan Zhou, Shaoxue Zeng, Jianhai Du, Mark C. Gillies

Faculty & Staff Scholarship

Abstract The human macula is more susceptible than the peripheral retina to developing blinding conditions such as age-related macular degeneration, diabetic retinopathy. A key difference between them may be the nature of their Mu¨ ller cells. We found primary cultured Mu¨ ller cells from macula and peripheral retina display significant morphological and transcriptomic differences. Macular Mu¨ ller cells expressed more phosphoglycerate dehydrogenase (PHGDH, a rate-limiting enzyme in serine synthesis) than peripheral Mu¨ ller cells. The serine synthesis, glycolytic and mitochondrial function were more activated in macular than peripheral Mu¨ ller cells. Serine biosynthesis is critical in defending against oxidative stress. …

Metabolic Deregulation Of The Blood-Outer Retinal Barrier In Retinitis Pigmentosa, Wei Wang, Ashwini Kini, Yekai Wang, Tingting Liu, Yao Chen, Eric Vukmanic, Douglas Emery, Yongqing Liu, Xiaoqin Lu, Lei Jin, San Joon Lee, Patrick Scott, Xiao Liu, Kevin Dean, Qingxian Lu, Enzo Fortuny, Robert James, Henry J. Kaplan, Jianhai Du, Douglas C. Dean

Faculty & Staff Scholarship

Retinitis pigmentosa (RP) initiates with diminished rod photoreceptor function, causing peripheral and nighttime vision loss. However, subsequent loss of cone function and high-resolution daylight and color vision is most debilitating. Visual pigment-rich photoreceptor outer segments (OS) undergo phagocytosis by the retinal pigment epithelium (RPE), and the RPE also acts as a blood-outer retinal barrier transporting nutrients, including glucose, to photoreceptors. We provide evidence that contact between externalized phosphatidylserine (PS) on OS tips and apical RPE receptors activates Akt, linking phagocytosis with glucose transport to photoreceptors for new OS synthesis. As abundant mutant rod OS tips shorten in RP, Akt activation …

Adp-Ribosylation Factor-Like 2 (Arl2) Regulates Cilia Stability And Development Of Outer Segments In Rod Photoreceptor Neurons, Zachary C. Wright, Yuriy Loskutov, Daniel Murphy, Peter Stoilov, Elena Pugacheva, Andrew F.X. Goldberg, Visvanathan Ramamurthy

Faculty & Staff Scholarship

Photoreceptor cells are specialized neurons with a sensory cilium carrying an elaborate membrane structure, the outer segment (OS). Inherited mutations in genes involved in ciliogenesis frequently result in OS malformation and blindness. ADP-ribosylation factor-like 2 (ARL2) has recently been implicated in OS formation through its association with Binder of ARL2 (BART or ARL2BP), a protein linked to inherited blinding disease. To test the role of ARL2 in vision we created a transgenic mouse model expressing a tagged-dominant active form of human ARL2 (ARL2-Q70L) under a rod-specific promoter. Transgenic ARL2-Q70L animals exhibit reduced photoreceptor cell function as early as post-natal day …

The Impact Of Conjunctival Flap Method And Drainage Cannula Diameter On Bleb Survival In The Rabbit Model, Cooper D. Rodgers, Alissa M. Meyer, Nicole C. Rosenberg, Zachary L. Lukowski, Jamie L. Schaefer, Gina M. Martorana, Monica A. Levine, Craig A. Meyers, Mark B. Sherwood

Faculty & Staff Scholarship

Purpose

To examine the effect of cannula diameter and conjunctival flap method on bleb survival in rabbits undergoing cannula-based glaucoma filtration surgery (GFS).

Methods

Twelve New Zealand White rabbits underwent GFS in both eyes. The twenty-four eyes were divided into four groups. Two of the four groups (N = 12) received limbus-based con- junctival flaps (LBCF), and the other two (N = 12) received fornix-based conjunctival flaps (FBCF). Six FBCF rabbit eyes were implanted with 22-gauge drainage tubes, and the other six were implanted with 26-gauge tubes. Likewise, six LBCF rabbits received 22-gauge drainage tubes and six received 26-gauge tubes. …

Acute Posterior Multifocal Placoid Pigment Epitheliopathy Associated With Gastrointestinal Stromal Tumor And Hurthle Cell Tumor, Daniel D. Kim, Ghassan Ghorayeb

Faculty & Staff Scholarship

Acute posterior multifocal placoid pigment epitheliopathy (APMPEE) is a chorioretinal inflammatory disease of unknown origin. Patients usually present with a rapid loss of central/paracentral vision over the course of a week in both eyes. The fundus exhibits rapid appearance of multiple deep subretinal yellow-white, flat lesions at the RPE/choriocapillaris level. This in turn causes changes of both the ellipsoid zone and RPE which can result in permanent central vision loss. The pathogenesis is controversial but is associated with a recent viral illness and can involve the central nervous system with concern for cerebral vasculitis. Rare reports of APMPEE associated with …

Isolated Inferior Rectus Muscle Entrapment Following Endoscopic Sinus Surgery, Scott Shapiro, Jamie L. Schaefer, Sumeet Gupta, John Nguyen, Brian Kellerymeyer

Faculty & Staff Scholarship

Orbital complications are known risks of endoscopic sinus surgery (ESS). The lamina papyracea and medial rectus muscle are the most commonly injured structures during ESS. Inferior rectus injury is more rare, with only one reported case of isolated inferior rectus injury in the literature. Guidelines for managing ESS-induced inferior rectus injury do not exist, and delayed intervention and management of adjacent sinuses may affect long-term outcomes such as persistent diplopia and disfigurement. In this report, we present a case of a 67-year-old man with diplopia due to isolated left inferior rectus muscle entrapment and injury from violation of the orbital …

High Myopic Photorefractive Keratectomy Outcomes With The Alcon Wavelight® Ex500 Excimer Laser, Mark D. Mifflin, Brent S. Betts, Jason Nguyen, Severin Pouly

Faculty & Staff Scholarship

Purpose: To present refractive outcomes from consecutive cases with the Alcon Wavelight® EX500 excimer laser using photorefractive keratectomy (PRK) in patients with high myopia. Methods: A retrospective chart review of consecutive cases of high myopic eyes ($6.0 Diopters [D]) undergoing PRK with the Alcon Wavelight EX500 excimer laser (Alcon Labo- ratories, Fort Worth, TX, USA) was done. Moderately high myopic eyes (6.0 to ,8.0 D [6 D]) were compared with high myopic eyes (8.0 D or greater [8 D]). Outcomes measured included pre- and postoperative refractive error, uncorrected distance visual acuity (UDVA), corrected distance visual acuity, spherical equivalent correction (SEQ), …

Farnesylation Of The Transducin G Protein Gamma Subunit Is A Prerequisite For Its Ciliary Targeting In Rod Photoreceptors, Celine Brooks, Joseph Murphy, Marycharmain Belcastro, Daniel Heller, Saravanan Kolandaivelu, Oleg Kisselev, Maxim Sokolov

Faculty & Staff Scholarship

Primary cilia are microtubule-based organelles, which protrude from the plasma membrane and receive a wide range of extracellular signals. Various cilia use G protein-coupled receptors (GPCRs) for the detection of these signals. For instance, vertebrate rod photoreceptors use their cilia (also called outer segments) as antennae detecting photons by GPCR rhodopsin. Rhodopsin recognizes incoming light and activates its G protein, transducin, which is composed of three subunits α, β, and γ. Similar to all G protein γ subunits, the transducin Gγ1 subunit undergoes C-terminal prenylation resulting in the addition of an isoprenoid farnesyl; however, the significance of this posttranslational modification …

Cost Effect Of Surgeon And Patient Discretion In Regard To Cataract Surgery, Tyler D. Oostra, Thomas F. Mauger

Faculty & Staff Scholarship

Purpose: The purpose of this study is to examine the cost effect of surgeon and patient discretion in regard to cataract surgery and how this affects population health care costs. Methods: A model of cataract progression was created from preexisting published data and combined with mortality data and Medicare cataract statistics to estimate the effect of mortality on decreasing the rate of cataract surgery if surgery was delayed until any cataract progression occurred.

Results: Five-year cataract progression rates were determined for a given patient age, sex, and type of cataract. Combined with 5-year death rates, delaying surgery until progression occurred …

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 …