Clinical Trials:

Fernando Paganelli, José A. Cardillo, Luiz A. S. Melo, Jr, David R. Lucena, Arnobio A. Silva, Jr, Anselmo G. Oliveira, Ana L. Höfling-Lima, Quan Dong Nguyen, Baruch D. Kuppermann, Rubens Belfort, Jr, and and the Brazilian Ocular Pharmacology and Pharmaceutical Technology Research Group (BOPP)

A Single Intraoperative Sub-Tenon’s Capsule Injection of Triamcinolone and Ciprofloxacin in a Controlled-Release System for Cataract Surgery
2009 50: 3041-3047. First Published on February 21 2009 as doi:10.1167/iovs.08-2920.
The present study substantiates a novel and more comprehensive therapeutic strategy for infection prophylaxis and to treat ocular inflammation associated with cataract surgery that employs a drug delivery system (DDS) to eliminate patient self-medication.
[Abstract] [Full Text] [PDF]  

Anatomy and Pathology:

Bertil Damato, Justyna Dopierala, Annelies Klaasen, Marcory van Dijk, Julie Sibbring, and Sarah E. Coupland

Multiplex Ligation-Dependent Probe Amplification of Uveal Melanoma: Correlation with Metastatic Death
2009 50: 3048-3055. First Published on January 31 2009 as doi:10.1167/iovs.08-3165.
Multiplex ligation-dependent probe amplification (MLPA) of uveal melanomas identifies abnormalities in chromosomes 1, 3, 6, and 8, which correlate with metastatic death. Metastasis occurs even with statistically insignificant MLPA results, probably because of the dilution effects of cellular heterogeneity, making it necessary to consider multiple risk factors simultaneously.
[Abstract] [Full Text] [PDF]  

Bärbel Rohrer, Qin Long, Beth Coughlin, R. Brooks Wilson, Yuxiang Huang, Fei Qiao, Peter H. Tang, Kannan Kunchithapautham, Gary S. Gilkeson, and Stephen Tomlinson

A Targeted Inhibitor of the Alternative Complement Pathway Reduces Angiogenesis in a Mouse Model of Age-Related Macular Degeneration
2009 50: 3056-3064. First Published on March 5 2009 as doi:10.1167/iovs.08-2222.
Polymorphisms interfering with the function of factor H, an inhibitor of the alternative pathway of complement activation, are associated with increased risk for age-related macular degeneration (AMD). The authors designed a targeted fH molecule (CR2-fH) consisting of the N-terminal region of mouse fH, which contains the alternative pathway inhibitory domain of the intact molecule, linked to a complement receptor 2 (CR2)–targeting fragment that binds complement activation products. Intravenously administered CR2-fH was found to effectively reduce CNV histologically and preserved retinal function even after delayed treatment after injury, which may open new avenues for the development of treatment strategies for AMD.
[Abstract] [Full Text] [PDF]  

Biochemistry and Molecular Biology:

Christophe Antczak, Carolyn Kloepping, Constantin Radu, Thorsten Genski, Lutz Müller-Kuhrt, Karsten Siems, Elisa de Stanchina, David H. Abramson, and Hakim Djaballah

Revisiting Old Drugs as Novel Agents for Retinoblastoma: In Vitro and In Vivo Antitumor Activity of Cardenolides
2009 50: 3065-3073. First Published on January 17 2009 as doi:10.1167/iovs.08-3158.
Revisiting some of the FDA-approved drugs for the purpose of identifying potent agents for retinoblastoma revealed that members of a well-known class of cardiotonic drugs constitute exciting candidates for treating retinoblastoma.
[Abstract] [Full Text] [PDF]  

Gregory H. Grossman, Gayle J. T. Pauer, Umadevi Narendra, Neal S. Peachey, and Stephanie A. Hagstrom

Early Synaptic Defects in tulp1^–/– Mice
2009 50: 3074-3083. First Published on February 14 2009 as doi:10.1167/iovs.08-3190.
This study shows that in tulp1^–/– mice the early-onset, severe photoreceptor degeneration is preceded by synaptic abnormalities and represents a phenotype not previously described. The data indicate that not only is Tulp1 critical for photoreceptor function and survival, but it is essential for the proper development of the photoreceptor synapse.
[Abstract] [Full Text] [PDF]  

Gaofeng Wang, Kylee L. Spencer, Brenda L. Court, Lana M. Olson, William K. Scott, Jonathan L. Haines, and Margaret A. Pericak-Vance

Localization of Age-Related Macular Degeneration-Associated ARMS2 in Cytosol, Not Mitochondria
2009 50: 3084-3090. First Published on February 28 2009 as doi:10.1167/iovs.08-3240.
The significant associations in ARMS2 and HTRA1 are with polymorphisms (SNP rs10490924 and rs1120638) in strong linkage disequilibrium (LD) that confer virtually identical risks, preventing differentiation at the statistical level. This paper addresses whether ARMS2 alone confers the disease risk by the mitochondrial pathway as suggested in the literature.
[Abstract] [Full Text] [PDF]  

Leendert van Steensel, Dion Paridaens, Benjamin Schrijver, Gemma M. Dingjan, Paul L. A. van Daele, P. Martin van Hagen, Willem A. van den Bosch, Hemmo A. Drexhage, Herbert Hooijkaas, and Willem A. Dik

Imatinib Mesylate and AMN107 Inhibit PDGF-Signaling in Orbital Fibroblasts: A Potential Treatment for Graves’ Ophthalmopathy
2009 50: 3091-3098. First Published on February 21 2009 as doi:10.1167/iovs.08-2443.
This study demonstrates that the tyrosine kinase inhibitors imatinib mesylate and AMN107 block PDGF-BB–induced orbital fibroblast activation. Therefore, these drugs should be considered for treatment of patients with Graves’ ophthalmopathy who do not respond to regular therapies.
[Abstract] [Full Text] [PDF]  

Marjo Volotinen, Jukka Mäenpää, Esko Kankuri, Olli Oksala, Olavi Pelkonen, Miki Nakajima, Tsuyoshi Yokoi, and Jukka Hakkola

Expression of Cytochrome P450 (CYP) Enzymes in Human Nonpigmented Ciliary Epithelial Cells: Induction of CYP1B1 Expression by TCDD
2009 50: 3099-3105. First Published on March 25 2009 as doi:10.1167/iovs.08-2790.
This study showed that the expression of CYP1B1, a causative disease gene for primary congenital glaucoma, is regulated by aryl hydrocarbon receptor ligand TCDD in the ciliary cell type.
[Abstract] [Full Text] [PDF]  

Renata G. Picciani, Anthony Diaz, Richard K. Lee, and Sanjoy K. Bhattacharya

Potential for Transcriptional Upregulation of Cochlin in Glaucomatous Trabecular Meshwork: A Combinatorial Bioinformatic and Biochemical Analytical Approach
2009 50: 3106-3111. First Published on December 20 2008 as doi:10.1167/iovs.08-3106.
The authors describe the combinatorial approach of bioinformatics and biochemical analyses to determine relative higher abundance of potential transcription factors that may bind putative promoter regions and affect cochlin protein expression in glaucomatous compared to normal TM. The approach presented here can be utilized for other potentially pathogenic proteins in a wide variety of tissues. Coupled transcription-translation assays and promoter mutations using TM nuclear extracts support the concept that cochlin overexpression in glaucoma is affected by the presence of promoter-associated transcription factors in the TM.
[Abstract] [Full Text] [PDF] Supplementary Tables  

Clinical and Epidemiologic Research:

Matthew Anthony Kirkman, Alex Korsten, Miriam Leonhardt, Konstantin Dimitriadis, Ireneaus F. De Coo, Thomas Klopstock, Philip G. Griffiths, Gavin Hudson, Patrick F. Chinnery, and Patrick Yu-Wai-Man

Quality of Life in Patients with Leber Hereditary Optic Neuropathy
2009 50: 3112-3115. First Published on February 28 2009 as doi:10.1167/iovs.08-3166.
This is the first study documenting the level of functional visual impairment in patients with Leber hereditary optic neuropathy (LHON), one of the most common primary mitochondrial DNA genetic disorders. The authors’ results clearly show that LHON has a severe negative impact on quality of life, and it results in the worst VF-14 score when compared to other acquired or inherited ophthalmic disorders.
[Abstract] [Full Text] [PDF]  

Yi-Ju Li, Jeremy A. Guggenheim, Anuradha Bulusu, Ravikanth Metlapally, Diana Abbott, Francois Malecaze, Patrick Calvas, Thomas Rosenberg, Sandrine Paget, Rosalind C. Creer, George Kirov, Michael J. Owen, Bei Zhao, Tristan White, David A. Mackey, and Terri L. Young

An International Collaborative Family-Based Whole-Genome Linkage Scan for High-Grade Myopia
2009 50: 3116-3127. First Published on March 25 2009 as doi:10.1167/iovs.08-2781.
This is the first large-scale, whole-genome linkage scan for high-grade myopia using single nucleotide polymorphisms and a large cohort of families. The outcomes of this study will contribute to the future identifications of genes that affect the development of high-grade myopia.
[Abstract] [Full Text] [PDF] Supplementary Tables  

Cornea:

LaTia Etheredge, Bradley P. Kane, and John R. Hassell

The Effect of Growth Factor Signaling on Keratocytes In Vitro and Its Relationship to the Phases of Stromal Wound Repair
2009 50: 3128-3136. First Published on February 21 2009 as doi:10.1167/iovs.08-3077.
This study shows that the levels of proliferation induced by the growth factors were inversely related to the level of collagen production. The authors suggest that FGF-2 initiates the hypercellular phase of corneal wound healing, whereas IGF-I and PDGF are involved in the restoration of a normal extracellular matrix.
[Abstract] [Full Text] [PDF]  

Xian Zhang, Linling Shen, Yiping Jin, Daniel R. Saban, Sunil K. Chauhan, and Reza Dana

Depletion of Passenger Leukocytes from Corneal Grafts: An Effective Means of Promoting Transplant Survival?
2009 50: 3137-3144. First Published on January 10 2009 as doi:10.1167/iovs.08-1899.
Three ex vivo strategies of passenger leukocyte depletion from corneal grafts were developed. However, the depletion of graft passenger leukocytes failed to have a significant effect on promoting corneal graft survival, even in the high-risk setting.
[Abstract] [Full Text] [PDF]  

Naoyuki Morishige, Naoyuki Yamada, Shinichiro Teranishi, Tai-ichiro Chikama, Teruo Nishida, and Atsushi Takahara

Detection of Subepithelial Fibrosis Associated with Corneal Stromal Edema by Second Harmonic Generation Imaging Microscopy
2009 50: 3145-3150. First Published on February 21 2009 as doi:10.1167/iovs.08-3309.
Second harmonic generation imaging microscopy detected the subepithelial fibrosis and fibroblastic cells in edematous corneas. The development of pathologic changes beginning 12 months after the onset of edema suggests that stromal edema may be a progressive disease.
[Abstract] [Full Text] [PDF]  

Takahiko Hayashi, Satoru Yamagami, Kazumi Tanaka, Seiichi Yokoo, Tomohiko Usui, Shiro Amano, and Nobuhisa Mizuki

Immunologic Mechanisms of Corneal Allografts Reconstituted from Cultured Allogeneic Endothelial Cells in an Immune-Privileged Site
2009 50: 3151-3158. First Published on February 28 2009 as doi:10.1167/iovs.08-2530.
Cultured corneal endothelial cell transplantation should be applied clinically in the near future. This study presented clinical features and immunologic mechanisms in a mouse cultured corneal endothelial cell transplantation model.
[Abstract] [Full Text] [PDF]  

Qi Chen, Jianhua Wang, Meixiao Shen, Chunyan Cai, Jianhua Li, Lele Cui, Jia Qu, and Fan Lu

Lower Volumes of Tear Menisci in Contact Lens Wearers with Dry Eye Symptoms
2009 50: 3159-3163. First Published on March 11 2009 as doi:10.1167/iovs.08-2794.
Tear meniscus volumes during short-term wear by soft contact lens wearers with dryness symptoms were investigated using real-time optical coherence tomography (OCT). Tear volumes in dry eye symptomatic wearers were found to be lower than in asymptomatic wearers at baseline and during lens wear, which possibly contributed to the dryness.
[Abstract] [Full Text] [PDF]  

Michelle L. McDonald, Yanru Wang, Shivaram Selvam, Tamako Nakamura, Robert H. Chow, Joel E. Schechter, Samuel C. Yiu, and Austin K. Mircheff

Cytopathology and Exocrine Dysfunction Induced in Ex Vivo Rabbit Lacrimal Gland Acinar Cell Models by Chronic Exposure to Histamine or Serotonin
2009 50: 3164-3175. First Published on March 25 2009 as doi:10.1167/iovs.08-2768.
Antimuscarinic receptor autoantibodies and inflammatory cytokines are not the only factors that can impair lacrimal secretion. A diversity of G protein-coupled receptor agonists also may cause exocrine dysfunction and cytopathology, offering a possible explanation for why dry eye disease presents with diverse manifestations.
[Abstract] [Full Text] [PDF]  

Stephen B. Kaye, Timothy Neal, Steven Nicholson, Jagoda Szkurlat, Sharon Bamber, Andrew C. Baddon, Sarah Anderson, Keeley Seddon, Nichola Dwyer, Andrew M. Lovering, and Godfrey Smith

Concentration and Bioavailability of Ciprofloxacin and Teicoplanin in the Cornea
2009 50: 3176-3184. First Published on February 14 2009 as doi:10.1167/iovs.08-3201.
This study investigates and proposes a method to determine the bioactivity of topically applied antimicrobials in the cornea. For ciprofloxacin, the bioavailability at the epithelial and endothelial surfaces is approximately 10% of the chemical concentration.
[Abstract] [Full Text] [PDF]  

Timothy T. McMahon, Linda S. Kim, Gerald A. Fishman, Edwin M. Stone, Xinping C. Zhao, Richard W. Yee, and Jarema Malicki

CRB1 Gene Mutations Are Associated with Keratoconus in Patients with Leber Congenital Amaurosis
2009 50: 3185-3187. First Published on April 30 2009 as doi:10.1167/iovs.08-2886.
In a clinical setting, subjects with genotyped Leber congenital amaurosis were examined via slit lamp examination and corneal topography for the presence of keratoconus. In this cohort, CRB1 mutations were associated with keratoconus.
[Abstract] [Full Text] [PDF]  

Dirk Bauer, Susanne Wasmuth, Maren Hennig, Hanna Baehler, Klaus-Peter Steuhl, and Arnd Heiligenhaus

Amniotic Membrane Transplantation Induces Apoptosis in T Lymphocytes in Murine Corneas with Experimental Herpetic Stromal Keratitis
2009 50: 3188-3198. First Published on February 28 2009 as doi:10.1167/iovs.08-3041.
The authors studied the anti-inflammatory mechanism of human amniotic membrane transplantation (AMT) applied on murine corneas with herpetic stromal keratitis. By AMT, T-cell–mediated immune response was suppressed, corneal T-cell apoptosis was induced, and proinflammatory cytokine and chemokine levels were reduced. Memory against HSV-1 was not affected.
[Abstract] [Full Text] [PDF]  

María A. del Buey, José A. Cristóbal, Francisco J. Ascaso, Laura Lavilla, and Elena Lanchares

Biomechanical Properties of the Cornea in Fuchs’ Corneal Dystrophy
2009 50: 3199-3202. First Published on February 28 2009 as doi:10.1167/iovs.08-3312.
Central corneal thickness (CCT) is taken into account as the only parameter to determine the corneal rigidity in vivo. The aim of this study was to investigate the effect of Fuchs’ corneal dystrophy (FCD) on corneal viscoelastic properties and the results of IOP readings in relation to changes in corneal hysteresis and CCT. There have been few previous studies to evaluate if corneal dystrophies induce changes in corneal biomechanical characteristics. Thus, FCD may cause an underestimation error in IOP measurement.
[Abstract] [Full Text] [PDF]  

Suksri Chotikavanich, Cintia S. de Paiva, De Quan Li, Joseph J. Chen, Fang Bian, William J. Farley, and Stephen C. Pflugfelder

Production and Activity of Matrix Metalloproteinase-9 on the Ocular Surface Increase in Dysfunctional Tear Syndrome
2009 50: 3203-3209. First Published on February 28 2009 as doi:10.1167/iovs.08-2476.
Tear MMP-9 activity was found to be a useful biomarker for diagnosing, classifying, and monitoring dysfunctional tear syndrome (DTS).
[Abstract] [Full Text] [PDF]  

Eye Movements, Strabismus, Amblyopia, and Neuro-Ophthalmology:

Aine Rice, Jérémie Nsengimana, Ian G. Simmons, Carmel Toomes, Janice Hoole, Colin E. Willoughby, Frances Cassidy, Grange A. Williams, Nick D. George, Eamonn Sheridan, Terri L. Young, Tim I. Hunter, Brendan T. Barrett, David B. Elliott, D. Tim Bishop, and Chris F. Inglehearn

Replication of the Recessive STBMS1 Locus but with Dominant Inheritance
2009 50: 3210-3217. First Published on February 14 2009 as doi:10.1167/iovs.07-1631.
Nonsyndromic strabismus is a common eye disorder, but only one recessive genetic susceptibility locus has been identified to date. The authors report the ascertainment of 12 UK families with replication of the STBMS1 locus but with dominant inheritance.
[Abstract] [Full Text] [PDF]  

Behzad Mansouri, Bruce C. Hansen, and Robert F. Hess

Disrupted Retinotopic Maps in Amblyopia
2009 50: 3218-3225. First Published on February 28 2009 as doi:10.1167/iovs.08-2914.
This is a study of the interrelationship of positional uncertainty, spatial distortion, and visual acuity loss in strabismic amblyopia.
[Abstract] [Full Text] [PDF]  

Jing-Xia Liu, Hugh J. Willison, and Fatima Pedrosa-Domellöf

Immunolocalization of GQ1b and Related Gangliosides in Human Extraocular Neuromuscular Junctions and Muscle Spindles
2009 50: 3226-3232. First Published on February 28 2009 as doi:10.1167/iovs.08-3333.
The authors investigated the distribution of anti-GQ1b, -GT1a, and -GD1b antibody binding in human extraocular muscles and showed the abundant and synaptic-specific binding of anti-ganglioside antibodies in the muscles. The findings support the possibility that the neuromuscular junctions of extraocular muscles might be a target for anti-disialylated ganglioside antibodies in Miller Fisher syndrome and related neuropathies.
[Abstract] [Full Text] [PDF]  

Glaucoma:

Farnaz Memarzadeh, Rohit Varma, Le-Tien Lin, Jignesh G. Parikh, Laurie Dustin, Ana Alcaraz, and Dean Eliott

Postoperative Use of Bevacizumab as an Antifibrotic Agent in Glaucoma Filtration Surgery in the Rabbit
2009 50: 3233-3237. First Published on January 31 2009 as doi:10.1167/iovs.08-2441.
Postoperative subconjunctival injection of bevacizumab is a useful adjunct for improving the success of trabeculectomy in the rabbit model.
[Abstract] [Full Text] [PDF]  

Neville N. Osborne, Guang-Yu Li, Dan Ji, Belmira L. Andrade da Costa, Rebecca J. Fawcett, Kui Dong Kang, and Kay D. Rittenhouse

Expression of Prostaglandin PGE₂ Receptors under Conditions of Aging and Stress and the Protective Effect of the EP2 Agonist Butaprost on Retinal Ischemia
2009 50: 3238-3248. First Published on March 5 2009 as doi:10.1167/iovs.08-3185.
Four types of PGE₂ receptors, designated EP1–EP4, are located to the inner retina of different aged rats. Ischemia/reperfusion results in inner retina damage and this is blunted by the EP2 receptor agonist butaprost.
[Abstract] [Full Text] [PDF]  

Andrew Turpin, Geoff P. Sampson, and Allison M. McKendrick

Combining Ganglion Cell Topology and Data of Patients with Glaucoma to Determine a Structure–Function Map
2009 50: 3249-3256. First Published on March 25 2009 as doi:10.1167/iovs.08-2492.
This paper introduces a computational model of axon growth and shows its use in deriving a structure–function map relating visual field data and sectoral ONH data. It also shows that using the fellow eye of participants to normalize data before computing the map assists in generating statistically significant correlations between field locations and ONH sectors.
[Abstract] [Full Text] [PDF]  

Immunology and Microbiology:

Tomoyuki Kamao, Tatsuhiko Miyazaki, Yoshiko Soga, Hiroaki Komori, Miho Terada, Yuichi Ohashi, and Masato Nose

Genetic Dissociation of Dacryoadenitis and Sialadenitis in a Sjögren’s Syndrome Mouse Model with Common and Different Susceptibility Gene Loci
2009 50: 3257-3265. First Published on February 14 2009 as doi:10.1167/iovs.08-3132.
Sjögren’s syndrome (SS) is a systemic autoimmune disease in which the main lesions are dacryoadenitis and sialadenitis. The susceptibility loci to each lesion and the association with both loci were determined in the SS mouse model MRL/lpr, to examine whether these lesions develop in a common genetic background. This study advanced the novel concept that dacryoadenitis and sialadenitis are under the control of common and different susceptibility loci with an allelic combination to lead a regular variation of pathologic phenotypes.
[Abstract] [Full Text] [PDF]  

Rebecca L. O'Brien, Molly A. Taylor, Jacqueline Hartley, Tanja Nuhsbaum, Steve Dugan, Kevin Lahmers, M. Kemal Aydintug, J. M. Wands, Christina L. Roark, and Willi K. Born

Protective Role of T Cells in Spontaneous Ocular Inflammation
2009 50: 3266-3274. First Published on January 17 2009 as doi:10.1167/iovs.08-2982.
Mice lacking T cells were found to develop keratitis spontaneously via an apparent autoimmune process. Females are more susceptible than males and the C57BL/10 background is required.
[Abstract] [Full Text] [PDF]  

Mandana Zandian, Raelene Belisle, Kevin R. Mott, Steven Nusinowitz, Florence M. Hofman, and Homayon Ghiasi

Optic Neuritis in Different Strains of Mice by a Recombinant HSV-1 Expressing Murine Interleukin-2
2009 50: 3275-3282. First Published on February 21 2009 as doi:10.1167/iovs.08-3211.
The results of this study demonstrate for the first time that a combination of viral infection and constitutive expression of IL-2, but not other cytokine genes or wild-type HSV-1, can result in demyelination and visual impairment in the optic nerves of ocularly infected mice.
[Abstract] [Full Text] [PDF]  

Lens:

Rajendra K. Gangalum and Suraj P. Bhat

B-crystallin: A Golgi-Associated Membrane Protein in the Developing Ocular Lens
2009 50: 3283-3290. First Published on February 14 2009 as doi:10.1167/iovs.08-3052.
This study demonstrates that B-crystallin, known to be a soluble protein, starts life as a Golgi-associated membrane protein; its status is determined by the developmentally controlled physical state of the Golgi, indicating that non-crystallin function is an innate component of the expression of a crystallin in the lens.
[Abstract] [Full Text] [PDF]  

Lars Hansen, Annemette Mikkelsen, Peter Nürnberg, Gudrun Nürnberg, Iram Anjum, Hans Eiberg, and Thomas Rosenberg

Comprehensive Mutational Screening in a Cohort of Danish Families with Hereditary Congenital Cataract
2009 50: 3291-3303. First Published on January 31 2009 as doi:10.1167/iovs.08-3149.
Despite considerable locus heterogeneity, a high mutation identification rate (71%) was achieved by analyzing a limited number of major cataract loci in 28 unrelated families and individuals with hereditary congenital cataract.
[Abstract] [Full Text] [PDF] Supplementary Table  

Robert M. Bigsby, Shailaja Valluri, Jennifer Lopez, Marc S. Mendonca, Andrea Caperell-Grant, Colleen DesRosiers, and Joseph R. Dynlacht

Ovarian Hormone Modulation of Radiation-Induced Cataractogenesis: Dose-Response Studies
2009 50: 3304-3310. First Published on February 28 2009 as doi:10.1167/iovs.08-3262.
Epidemiologic data on the effects of ovarian hormones in cataractogenesis are conflicting. In a rat model of radiation-induced cataracts, estrogen is shown to enhance the rate of cataract formation.
[Abstract] [Full Text] [PDF]  

Beryl J. Ortwerth, Jaya Bhattacharyya, and Ekaterina Shipova

Tryptophan Metabolites from Young Human Lenses and the Photooxidation of Ascorbic Acid by UVA Light
2009 50: 3311-3319. First Published on March 5 2009 as doi:10.1167/iovs.08-2927.
Human lenses contain low-molecular-weight compounds that absorb UVA light initiating the oxidation of ascorbic acid, producing compound(s) capable of glycating lens proteins. Although previously identified as inactive filter compounds, they cause UVA photooxidation in the absence of oxygen, similar to conditions present in human lens tissue.
[Abstract] [Full Text] [PDF]  

Physiology and Pharmacology:

David F. Woodward, Siv F. E. Nilsson, Carol B. Toris, Alexander B. Kharlamb, Amelia L. Nieves, and Achim H.-P. Krauss

Prostanoid EP₄ Receptor Stimulation Produces Ocular Hypotension by a Mechanism That Does Not Appear to Involve Uveoscleral Outflow
2009 50: 3320-3328. First Published on February 21 2009 as doi:10.1167/iovs.08-3031.
The prostanoid EP₄ receptor uniquely lowers intraocular pressure by stimulating trabecular outflow. This sets it apart from other prostanoid receptors, which increase uveoscleral outflow.
[Abstract] [Full Text] [PDF]  

Travis W. Hein, Yi Ren, Zhaoxu Yuan, Wenjuan Xu, Sonal Somvanshi, Taiji Nagaoka, Akitoshi Yoshida, and Lih Kuo

Functional and Molecular Characterization of the Endothelin System in Retinal Arterioles
2009 50: 3329-3336. First Published on January 17 2009 as doi:10.1167/iovs.08-3129.
The authors used an isolated vessel approach to study the direct vasomotor influence of endothelin (ET)-1 receptor and endothelin-converting enzyme (ECE)-1 activation on porcine retinal arterioles and to identify the molecular distribution of the ET system in these microvessels. They provide direct evidence showing that retinal arterioles possess endothelial/smooth muscle ECE-1 and that its activation is sufficient to elicit ET-1–mediated, smooth muscle ETA receptor–dependent constriction.
[Abstract] [Full Text] [PDF]  

Jesica Martin, Pradeep Malreddy, Takeo Iwamoto, Lisa C. Freeman, Harriet J. Davidson, John M. Tomich, and Bruce D. Schultz

NC-1059: A Channel-Forming Peptide That Modulates Drug Delivery across In Vitro Corneal Epithelium
2009 50: 3337-3345. First Published on February 21 2009 as doi:10.1167/iovs.08-3053.
NC-1059 is a novel synthetic peptide that transiently and reversibly allows small molecules to cross the tight junctions between corneal epithelial cells. Such functionality will enhance greatly the ability to achieve effective concentrations of therapeutic agents in ocular tissues.
[Abstract] [Full Text] [PDF]  

Joseph B. Ciolino, Todd R. Hoare, Naomi G. Iwata, Irmgard Behlau, Claes H. Dohlman, Robert Langer, and Daniel S. Kohane

A Drug-Eluting Contact Lens
2009 50: 3346-3352. First Published on January 10 2009 as doi:10.1167/iovs.08-2826.
Using a thin drug-PLGA film coated with pHEMA, a prototype contact lens has been designed for sustained drug delivery. This system could potentially be used as a platform for ocular drug delivery with widespread therapeutic applications.
[Abstract] [Full Text] [PDF]  

William M. Dismuke, Najam A. Sharif, and Dorette Z. Ellis

Human Trabecular Meshwork Cell Volume Decrease by NO-Independent Soluble Guanylate Cyclase Activators YC-1 and BAY-58-2667 Involves the BK_Ca Ion Channel
2009 50: 3353-3359. First Published on February 21 2009 as doi:10.1167/iovs.08-3127.
Managing IOP by surgery or medication is the only known viable treatment for glaucoma. Therefore, understanding the signal transduction pathway by which the NO-independent activator of sGC, YC-1, and BAY-58-2667 regulates TM cell function may provide new targets for the development of therapeutics in the treatment of glaucoma.
[Abstract] [Full Text] [PDF]  

Retina:

Grace Byfield, Steve Budd, and M. Elizabeth Hartnett

The Role of Supplemental Oxygen and JAK/STAT Signaling in Intravitreous Neovascularization in a ROP Rat Model
2009 50: 3360-3365. First Published on March 5 2009 as doi:10.1167/iovs.08-3256.
In a relevant model of retinopathy of prematurity, in which the effect of VEGF is reduced, JAK/STAT signaling plays a significant role in the development of intravitreous neovascularization.
[Abstract] [Full Text] [PDF]  

Amir H. Kashani, Pearse A. Keane, Laurie Dustin, Alexander C. Walsh, and Srinivas R. Sadda

Quantitative Subanalysis of Cystoid Spaces and Outer Nuclear Layer Using Optical Coherence Tomography in Age-Related Macular Degeneration
2009 50: 3366-3373. First Published on January 24 2009 as doi:10.1167/iovs.08-2691.
Manual segmentation of OCT images using custom software allows quantification of intraretinal cystoid spaces and the outer nuclear layer. The volume of intraretinal cystoid space did not correlate with visual acuity, and adjustment of retinal thickness measurements for cystoid space did not alter visual acuity correlations. An increased total volume of outer nuclear layer was modestly associated with decreased vision in neovascular AMD.
[Abstract] [Full Text] [PDF]  

Manal Hajali, Gerald A. Fishman, Robert J. Anderson, and J. Jason McAnany

Interocular Difference and Duration for Doubling of the Minimal Angle of Visual Resolution in Patients with Stargardt Disease
2009 50: 3374-3377. First Published on February 21 2009 as doi:10.1167/iovs.08-2775.
Knowledge of factors related to both change in visual acuity and degrees of differences in interocular acuity will have relevance for future treatment trials in patients with Stargardt disease. This knowledge will also have potential value in counseling patients about visual acuity loss from the disease. In this report, the authors determined the maximum degree of interocular difference in visual acuity and its relationship to the mean acuity of the two eyes as well as the association between baseline visual acuity and patient age to longitudinal change in acuity.
[Abstract] [Full Text] [PDF]  

Pearse A. Keane, Sandra Liakopoulos, Renu V. Jivrajka, Karen T. Chang, Tarek Alasil, Alexander C. Walsh, and Srinivas R. Sadda

Evaluation of Optical Coherence Tomography Retinal Thickness Parameters for Use in Clinical Trials for Neovascular Age-Related Macular Degeneration
2009 50: 3378-3385. First Published on March 5 2009 as doi:10.1167/iovs.08-2728.
Manual correction of errors in automated StratusOCT segmentation may be required to allow accurate interpretation of anatomic outcomes for clinical trials of neovascular AMD. In addition, although measurement of the foveal central subfield remains preferable for assessment of central retinal thickness, accurate measurement of the foveal center point may represent an adequate alternative when the foveal central subfield is unavailable.
[Abstract] [Full Text] [PDF]  

Kyu Hyung Park, Brooke L. Fridley, Euijung Ryu, Nirubol Tosakulwong, and Albert O. Edwards

Complement Component 3 (C3) Haplotypes and Risk of Advanced Age-Related Macular Degeneration
2009 50: 3386-3393. First Published on February 21 2009 as doi:10.1167/iovs.08-3231.
Genetically determined changes in the protein sequence of complement component 3 (C3) increased the risk of development of AMD by 1.8-fold for one risk allele or 2.4-fold for two risk alleles and were preferentially associated with advanced AMD. Haplotypes in the 3' end of C3 may have an independent association with AMD.
[Abstract] [Full Text] [PDF]  

Hetian Lei, Gisela Velez, Peter Hovland, Tatsuo Hirose, Debra Gilbertson, and Andrius Kazlauskas

Growth Factors Outside the PDGF Family Drive Experimental PVR
2009 50: 3394-3403. First Published on March 25 2009 as doi:10.1167/iovs.08-3042.
Vitreal growth factors outside of the PDGF family activate the PDGF receptor (PDGFR), and thereby promote the contraction of cells in an in vitro setting and experimental PVR. PDGFR is a particularly attractive therapeutic target for PVR because it is activated by many of the growth factors in the vitreous.
[Abstract] [Full Text] [PDF]  

Hille W. van Dijk, Pauline H. B. Kok, Mona Garvin, Milan Sonka, J. Hans DeVries, Robert P. J. Michels, Mirjam E. J. van Velthoven, Reinier O. Schlingemann, Frank D. Verbraak, and Michael D. Abràmoff

Selective Loss of Inner Retinal Layer Thickness in Type 1 Diabetic Patients with Minimal Diabetic Retinopathy
2009 50: 3404-3409. First Published on January 17 2009 as doi:10.1167/iovs.08-3143.
Decreased total retinal thickness in type 1 diabetic patients with minimal retinopathy relative to normal controls is due to a selective thinning of inner retinal layers and supports the concept that early diabetic retinopathy includes a neurodegenerative component.
[Abstract] [Full Text] [PDF]  

Aya Takeuchi, Masaru Takeuchi, Kosuke Oikawa, Koh-hei Sonoda, Yoshihiko Usui, Yoko Okunuki, Atsunobu Takeda, Yuji Oshima, Keiichi Yoshida, Masahiko Usui, Hiroshi Goto, and Masahiko Kuroda

Effects of Dioxin on Vascular Endothelial Growth Factor (VEGF) Production in the Retina Associated with Choroidal Neovascularization
2009 50: 3410-3416. First Published on January 31 2009 as doi:10.1167/iovs.08-2299.
Dioxin acts on ocular tissues via the AhR pathway, promotes VEGF production in the retina and retinal pigment epithelium, and exacerbates the development of choroidal neovascularization.
[Abstract] [Full Text] [PDF]  

Christian Ahlers, Isabelle Golbaz, Elisa Einwallner, Roman Dunavölgyi, Panagiotis Malamos, Geraldine Stock, Christian Pruente, and Ursula Schmidt-Erfurth

Identification of Optical Density Ratios in Subretinal Fluid as a Clinically Relevant Biomarker in Exudative Macular Disease
2009 50: 3417-3424. First Published on January 24 2009 as doi:10.1167/iovs.08-2759.
Optical density ratios allow differentiation between macular diseases with subretinal fluid and may have a prognostic potential in neovascular age-related macular degeneration.
[Abstract] [Full Text] [PDF]  

Peter J. Francis, Shaomei Wang, Yi Zhang, Anna Brown, Thomas Hwang, Trevor J. McFarland, Brett G. Jeffrey, Bin Lu, Lynda Wright, Binoy Appukuttan, David J. Wilson, J. Timothy Stout, Martha Neuringer, David M. Gamm, and Raymond D. Lund

Subretinal Transplantation of Forebrain Progenitor Cells in Nonhuman Primates: Survival and Intact Retinal Function
2009 50: 3425-3431. First Published on February 21 2009 as doi:10.1167/iovs.08-2908.
Cell-based therapy, in which cells are transplanted into the subretinal space, has shown efficacy in treating retinal degenerative disease in rodents. In this paper, the authors show that these same cells can safely be transplanted to and survive in a nonhuman primate.
[Abstract] [Full Text] [PDF]  

Ute E. K. Wolf-Schnurrbusch, Lala Ceklic, Christian K. Brinkmann, Milko E. Iliev, Manuel Frey, Simon P. Rothenbuehler, Volker Enzmann, and Sebastian Wolf

Macular Thickness Measurements in Healthy Eyes Using Six Different Optical Coherence Tomography Instruments
2009 50: 3432-3437. First Published on February 21 2009 as doi:10.1167/iovs.08-2970.
Measurements of central retinal thickness vary between different OCT systems. Therefore, the different OCT systems cannot be used interchangeably for the measurement of macular thickness in clinical practice.
[Abstract] [Full Text] [PDF]  

Berrin Avci, Remzi Avci, Ümit Übeyt Inan, and Berkant Kaderli

Comparative Evaluation of Apoptotic Activity in Photoreceptor Cells after Intravitreal Injection of Bevacizumab and Pegaptanib Sodium in Rabbits
2009 50: 3438-3446. First Published on February 28 2009 as doi:10.1167/iovs.08-2871.
This study provides evidence that anti-VEGF treatment with pegaptanib sodium, an antagonist of the VEGF-165 isoform, which is primarily responsible for pathogenic ocular neovascularization, or with bevacizumab, an antagonist of all VEGF isoforms, causes increasing apoptosis in photoreceptor cells of rabbit eyes.
[Abstract] [Full Text] [PDF]  

Jian-Jang You, Chang-Hao Yang, Muh-Shy Chen, and Chung-May Yang

Cysteine-rich 61, a Member of the CCN Family, as a Factor Involved in the Pathogenesis of Proliferative Diabetic Retinopathy
2009 50: 3447-3455. First Published on March 5 2009 as doi:10.1167/iovs.08-2603.
Cysteine-rich 61 (Cyr61), a member of the CCN family, is an angiogenic factor. The authors investigated the angiogenic effects of Cyr61 in in vitro and in vivo experimental models of retinal angiogenesis. The authors further examined its interaction with VEGF and measured the vitreous levels of Cyr61 to examine its role in PDR. It may interact with VEGF in a synergetic manner. Vitreous levels of Cyr61 are significantly elevated in patients with PDR. Cyr61 may be involved in the pathogenesis of PDR.
[Abstract] [Full Text] [PDF]  

Geereddy Bhanuprakash Reddy, Vidyullatha Vasireddy, Md Nawajes A. Mandal, Mrudula Tiruvalluru, Xiaofei F. Wang, Monica M. Jablonski, Giridharan Nappanveettil, and Radha Ayyagari

A Novel Rat Model with Obesity-Associated Retinal Degeneration
2009 50: 3456-3463. First Published on April 15 2009 as doi:10.1167/iovs.08-2498.
A strong association between retinal degeneration and obesity has been shown in patients. However, the molecular basis of increased risk for retinal degeneration in obesity is not known. Thus, an animal model with obesity and retinal degeneration would greatly aid in understanding obesity-associated retinal degeneration. In the present study, the authors describe retinal abnormalities in a novel rat model (WNIN-Ob) with spontaneously developed obesity.
[Abstract] [Full Text] [PDF] Supplementary Tables  

Fred K. Chen, Praveen J. Patel, Wen Xing, Catey Bunce, Catherine Egan, Adnan T. Tufail, Peter J. Coffey, Gary S. Rubin, and Lyndon Da Cruz

Test–Retest Variability of Microperimetry Using the Nidek MP1 in Patients with Macular Disease
2009 50: 3464-3472. First Published on March 25 2009 as doi:10.1167/iovs.08-2926.
In this prospective study of test–retest variability of retinal sensitivity measures using the Nidek MP1, the authors reported the limit of change in different parameters that may be attributable to the intrinsic noise in the system.
[Abstract] [Full Text] [PDF]  

Retinal Cell Biology:

Ping Yang, Jillian Tyrrell, Ian Han, and Glenn J. Jaffe

Expression and Modulation of RPE Cell Membrane Complement Regulatory Proteins
2009 50: 3473-3481. First Published on January 24 2009 as doi:10.1167/iovs.08-3202.
In this study, the authors have determined that distribution and regulation by cytokines and oxidants of human and mouse RPE membrane complement regulatory proteins (mCRPs). The distribution and regulation of these mCRPs vary in a species-specific manner, and increased cell mCRPs may help to protect RPE cells from complement- and oxidant-mediated injury in diseases such as AMD.
[Abstract] [Full Text] [PDF]  

Danian Gu, William A. Beltran, Sue Pearce-Kelling, Zexiao Li, Gregory M. Acland, and Gustavo D. Aguirre

Steroids Do Not Prevent Photoreceptor Degeneration in the Light-Exposed T4R Rhodopsin Mutant Dog Retina Irrespective of AP-1 Inhibition
2009 50: 3482-3494. First Published on February 21 2009 as doi:10.1167/iovs.08-3111.
AP-1 has been proposed as the key intermediate linking exposure to light and photoreceptor cell death in light damage; inhibition of AP-1 associated with steroid administration prevents light damage. The authors demonstrate that systemic dexamethasone, in contrast to intravitreal triamcinolone, inhibits AP-1 activation, but neither treatment prevents photoreceptor degeneration.
[Abstract] [Full Text] [PDF]  

Corina Bobu and David Hicks

Regulation of Retinal Photoreceptor Phagocytosis in a Diurnal Mammal by Circadian Clocks and Ambient Lighting
2009 50: 3495-3502. First Published on February 21 2009 as doi:10.1167/iovs.08-3145.
The influence of lighting on rod and cone phagocytosis in a diurnal species is unknown. These experiments demonstrate both light- and clock-driven mechanisms underlying phagocytic timing and amplitude and further show a dramatic effect of prolonged lighting on cone behavior.
[Abstract] [Full Text] [PDF]  

Takayuki Baba, Rhonda Grebe, Takuya Hasegawa, Imran Bhutto, Carol Merges, D. Scott McLeod, and Gerard A. Lutty

Maturation of the Fetal Human Choriocapillaris
2009 50: 3503-3511. First Published on March 5 2009 as doi:10.1167/iovs.08-2614.
This study suggests that human choriocapillaris endothelial cells (ECs) and their precursors have several mature functional characteristics at 9 weeks’ gestation (WG), well before they are structurally mature. Although ECs make tight junctions early in development, continuous fenestrations and broad, oval-shaped lumens occur much later in development (21–22 WG), when pericyte maturation (TEM and -smooth muscle actin) is apparent as well.
[Abstract] [Full Text] [PDF]  

Shunsuke Kubota, Toshihide Kurihara, Hiroshi Mochimaru, Shingo Satofuka, Kousuke Noda, Yoko Ozawa, Yuichi Oike, Susumu Ishida, and Kazuo Tsubota

Prevention of Ocular Inflammation in Endotoxin-Induced Uveitis with Resveratrol by Inhibiting Oxidative Damage and Nuclear Factor–B Activation
2009 50: 3512-3519. First Published on March 11 2009 as doi:10.1167/iovs.08-2666.
Resveratrol prevented EIU-associated cellular and molecular inflammatory responses via inhibiting oxidative damage and redox-sensitive NF-B activation. The current data suggest the potential use of resveratrol as a therapeutic agent to reduce ocular inflammation.
[Abstract] [Full Text] [PDF]  

Visual Psychophysics and Physiological Optics:

Shrikant R. Bharadwaj, Indu Vedamurthy, and Clifton M. Schor

Short-Term Adaptive Modification of Dynamic Ocular Accommodation
2009 50: 3520-3528. First Published on February 28 2009 as doi:10.1167/iovs.08-2577.
This investigation provides evidence of short-term adaption of dynamic ocular accommodation in adults in response to optically induced changes in neuromuscular effort.
[Abstract] [Full Text] [PDF]  

Qianying Gao, Xiang Chen, Jian Ge, Yongji Liu, Zhaoxin Jiang, Zhi Lin, and Yaqin Liu

Refractive Shifts in Four Selected Artificial Vitreous Substitutes Based on Gullstrand-Emsley and Liou-Brennan Schematic Eyes
2009 50: 3529-3534. First Published on March 5 2009 as doi:10.1167/iovs.08-2802.
Artificial vitreous substitutes often induce unexpected refractive shifts. The authors compared refractive shifts based on Gullstrand-Emsley and Liou-Brennan schematic eyes after filling with silicone oil, heavy silicone oil, hydrogels, and encapsuled balanced salt solution.
[Abstract] [Full Text] [PDF]  

Erratum:

ERRATUM
2009 50: 3136. [Full Text] [PDF]  

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