Ophthalmology Commons^™

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

Wills Eye Hospital Papers

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

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

Accumulation Of Rhodopsin In Late Endosomes Triggers Photoreceptor Cell Degeneration, Yashodhan Chinchore, Amitavo Mitra, Patrick J. Dolph, Norbert Perrimon

Dartmouth Scholarship

Progressive retinal degeneration is the underlying feature of many human retinal dystrophies. Previous work using Drosophila as a model system and analysis of specific mutations in human rhodopsin have uncovered a connection between rhodopsin endocytosis and retinal degeneration. In these mutants, rhodopsin and its regulatory protein arrestin form stable complexes, and endocytosis of these complexes causes photoreceptor cell death. In this study we show that the internalized rhodopsin is not degraded in the lysosome but instead accumulates in the late endosomes. Using mutants that are defective in late endosome to lysosome trafficking, we were able to show that rhodopsin accumulates …

High-Resolution Analysis Of Dna Copy Number Alterations In Patients With Primary Open-Angle Glaucoma., Khaled K Abu-Amero, Ali Hellani, Patrick Bender, George L. Spaeth, Jonathan Myers, L Jay Katz, Marlene Moster, Thomas M Bosley

Wills Eye Hospital Papers

PURPOSE: To determine whether patients with isolated primary open-angle glaucoma (POAG) have evidence of chromosomal copy number alterations.

METHODS: Twenty-seven Caucasian and African-American POAG patients and 12 ethnically matched controls were carefully screened for possible glaucoma and tested for chromosomal copy number alterations using high resolution array comparative genomic hybridization.

RESULTS: No POAG patient had evidence of chromosomal copy number alterations when compared to normal ethnically matched controls. Additionally, there was no evidence of somatic mosaicism in any tested POAG patient.

CONCLUSIONS: Chromosomal deletions and/or duplications were not detected in POAG patients as compared to controls. Other chromosomal imbalances such …

Transcriptional Regulatory Network Analysis During Epithelial-Mesenchymal Transformation Of Retinal Pigment Epithelium., Craig H Pratt, Rajanikanth Vadigepalli, Praveen Chakravarthula, Gregory E Gonye, Nancy J Philp, Gerald B Grunwald

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

PURPOSE: Phenotypic transformation of retinal pigment epithelial (RPE) cells contributes to the onset and progression of ocular proliferative disorders such as proliferative vitreoretinopathy (PVR). The formation of epiretinal membranes in PVR may involve an epithelial-mesenchymal transformation (EMT) of RPE cells as part of an aberrant wound healing response. While the underlying mechanism remains unclear, this likely involves changes in RPE cell gene expression under the control of specific transcription factors (TFs). Thus, the purpose of the present study was to identify TFs that may play a role in this process.

METHODS: Regulatory regions of genes that are differentially regulated during …

Neural Reprogramming In Retinal Degeneration, Robert E Marc, Bryan W Jones, James R Anderson, Krista Kinard, David W Marshak, John H Wilson, Theodore Wensel, Robert J Lucas

Faculty, Staff and Student Publications

PURPOSE: Early visual defects in degenerative diseases such as retinitis pigmentosa (RP) may arise from phased remodeling of the neural retina. The authors sought to explore the functional expression of ionotropic (iGluR) and group 3, type 6 metabotropic (mGluR6) glutamate receptors in late-stage photoreceptor degeneration.

METHODS: Excitation mapping with organic cations and computational molecular phenotyping were used to determine whether retinal neurons displayed functional glutamate receptor signaling in rodent models of retinal degeneration and a sample of human RP.

RESULTS: After photoreceptor loss in rodent models of RP, bipolar cells lose mGluR6 and iGluR glutamate-activated currents, whereas amacrine and ganglion …

Patient Education In Glaucoma: What Do Patients Know About Glaucoma?, Vital Paulino Costa, George L Spaeth, Maura Smith, Cordelia Uddoh, José Paulo Cabral Vasconcellos, Newton Kara-José

Wills Eye Hospital Papers

PURPOSE: To evaluate the knowledge glaucoma patients have about their disease and its treatment.

METHODS: One hundred and eighty-three patients were interviewed at the Glaucoma Service of Wills Eye Hospital (Philadelphia, USA, Group 1) and 100 at the Glaucoma Service of University of Campinas (Campinas, Brazil, Group 2). An informal, relaxed atmosphere was created by the interviewer before asking a list of 18 open-ended questions.

RESULTS: In Group 1, 44% of the 183 patients did not have an acceptable idea about what glaucoma is, 30% did not know the purpose of the medications they were taking, 47% were not aware …

Loss Of Sparc-Mediated Vegfr-1 Suppression After Injury Reveals A Novel Antiangiogenic Activity Of Vegf-A, Miho Nozaki, Eiji Sakurai, Brian J. Raisler, Judit Z. Baffi, Jassir Witta, Yuichiro Ogura, Rolf A. Brekken, E Helene Sage, Balamurali K. Ambati, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Publications

VEGF-A promotes angiogenesis in many tissues. Here we report that choroidal neovascularization (CNV) incited by injury was increased by excess VEGF-A before injury but was suppressed by VEGF-A after injury. This unorthodox antiangiogenic effect was mediated via VEGFR-1 activation and VEGFR-2 deactivation, the latter via Src homology domain 2-containing (SH2-containing) tyrosine phosphatase-1 (SHP-1). The VEGFR-1-specific ligand placental growth factor-1 (PlGF-1), but not VEGF-E, which selectively binds VEGFR-2, mimicked these responses. Excess VEGF-A increased CNV before injury because VEGFR-1 activation was silenced by secreted protein, acidic and rich in cysteine (SPARC). The transient decline of SPARC after injury revealed a temporal …