Novartis Foundation Symposium 255

RETINAL DYSTROPHIES:

FUNCTIONAL GENOMICS TO GENE THERAPY

2004

RETINAL DYSTROPHIES:

FUNCTIONAL GENOMICS TO GENE THERAPY

The Novartis Foundation is an international scienti¢c and educational charity (UK Registered Charity No. 313574). Known until September 1997 as the Ciba Foundation, it was established in 1947 by the CIBA company of Basle, which merged with Sandoz in 1996, to form Novartis. The Foundation operates independently in London under English trust

law. It was formally opened on 22 June 1949.

The Foundation promotes the study and general knowledge of science and in particular encourages international co-operation in scienti¢c research. To this end, it organizes internationally acclaimed meetings (typically eight symposia and allied open meetings and 15^20 discussion meetings each year) and publishes eight books per year featuring the presented papers and discussions from the symposia. Although primarily an operational rather than a grant-making foundation, it awards bursaries to young scientists to attend the symposia and afterwards work with one of the other participants.

The Foundation’s headquarters at 41 Portland Place, London W1B 1BN, provide library facilities, open to graduates in science and allied disciplines. Media relations are fostered by regular press conferences and by articles prepared by the Foundation’s Science Writer in Residence. The Foundation o¡ers accommodation and meeting facilities to visiting scientists and their societies.

The Foundation Fighting Blindness (FFB), formerly the Retinitis Pigmentosa Foundation, is a non-pro¢t foundation dedicated to supporting research

to discover causes, prevention, treatments and cures for inherited retinal degenerative diseases. Since its inception in 1971, The FFB has raised more than US$150 million for retinal degenerative disease research in the USA and Europe.

Through an early scienti¢c focus on support for genetic research, The FFB became

a driving force for discovery and cloning of genes and identi¢cation of mutations that cause various forms of inherited retinal degenerative disease. The Foundation research programs now encompass 10 basic areas: Cell Biology, Clinical Studies, Ocular Drug Delivery, Genetics, Gene Therapy, Nutrition, Pharmaceutical Therapy, Pre-clinical Studies, Stem Cells/Transplantation, and Surgery/Visual Prosthetics. Research projects supported by The FFB are peer-reviewed by independent experts and by members of The FFB Scienti¢c Advisory Board. FFB conducts meetings to explore the state of basic and clinical science related to inherited retinal degenerative diseases. These meetings include workshops on basic and clinical scienti¢c topics, clinical trial advisory panels, scienti¢c advisory board meetings and patient-oriented educational seminars. In addition,

The FFB an active Medical Therapy program in which alliances with the academic, government and corporate collaborations are utilized to accelerate the translation of basic research into clinically applicable therapies for retinal degenerative disease.

Novartis Foundation Symposium 255

RETINAL DYSTROPHIES:

FUNCTIONAL GENOMICS TO GENE THERAPY

2004

Copyright & Novartis Foundation 2004

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Novartis Foundation Symposium 255 ix+216 pages, 34 ¢gures, 7 tables

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subunit assembly in autosomal dominant retinitis pigmentosa linked to mutations in peripherin 2 95

Discussion 113

Thierry Le¤veillard, Saddek Mohand-Sa|«d, Anne Claire Fintz, George Lambrou and Jose¤-Alain Sahel The search for rod-dependent cone viability factors, secreted factors promoting cone viability 117

Discussion 127

Itay Chowers, Noriko Esumi, Peter Campochiaro and Donald J. Zack

Studies on retinal and retinal pigment epithelial gene expression 131

Discussion 145

J.Yu, A. J. Mears, S.Yoshida, R. Farjo,T. A. Carter, D. Ghosh, A. Hero, C. Barlow and A. Swaroop From disease genes to cellular pathways: a progress report 147

Discussion 160

WilliamW. Hauswirth, Quihong Li, Brian Raisler, Adrian M.Timmers, Kenneth I. Berns, John G. Flannery, Matthew M. LaVail and

Alfred S. Lewin Range of retinal diseases potentially treatable by AAV-vectored gene therapy 179

Discussion 188

Frans Cremers Department of Human Genetics, University Medical Center Nijmegen, PO Box 9101, 6500 HB Nijmegen,The Netherlands

Stephen P. Daiger Human Genetics Center, School of Public Health,

The University of Texas Health Science Center, 1200 Herman Pressler Street, Houston,TX 77030, USA

Thaddeus Dryja Massachusetts Eye & Ear In¢rmary, 243 Charles Street, Boston, MA 02114-3096, USA

Debora B. Farber Jules Stein Eye Institute, UCLA School of Medicine, 100 Stein Plaza, Los Angeles, CA 90095-7000, USA

Martin Friedlander Department of Cell Biology,The Scripps Research Institute, 10550 NorthTorrey Pines Road, MB-28, LaJolla, CA 92037, USA

Andreas Gal Institute for Human Genetics, Univ-Krankenhaus Eppendorf, Butenfeld 42, Hamburg, D-22529, Germany

Paul Hargrave Ophthalmology, University of Florida, Box 100284, 1600 SW Archer Road, Gainesville, FL 32610-0284, USA

William Hauswirth Ophthalmology and Molecular Genetics, Box 100266, 1600 SWArcher Road, University of Florida, Gainesville, FL 32610-0266, USA

David M. Hunt Division of Molecular Genetics, Institute of Ophthalmology, 11^43 Bath Street, London EC1V 9EL, UK

Michael Kaleko GeneticTherapy, Inc., 9 West Watkins Mill Road, Gaithersburg, MD 20878, USA

George N. Lambrou Novartis Ophthalmics AG,WKL-127.1.06, PO Box, CH-4002 Basel, Switzerland

Matthew LaVail BeckmanVision Center, UCSF School of Medicine, 10 Kirkham Street (Room K-120), San Francisco, CA 94143-0730, USA

Roderick McInnes Room 11101ElmWing,The Research Institute, Hospital for Sick Children, 555 UniversityAvenue,Toronto, Ontario M5G 1X8, Canada

Robert S. Molday Biochemistry/Molecular Biology, 2146 Health Sciences Mall, University of British Columbia,Vancouver, BC V6T 1Z3, Canada

Jeremy Nathans Johns Hopkins Medical School, PCTB Room 805, 725 North Wolfe Street, Baltimore, MD 21205-2185, USA

Jose¤-Alain Sahel Chef de Service, CHNO des Quinze-Vingts, 28 rue de Charenton, F-75557 Paris Cedex 12, France

Paul Sieving National Institutes of Health, National Eye Institute, 31 Center Drive, Building 31 6A-03, MSC 2510, MD 20892-2510, USA

Anand Swaroop Ophthalmology, University of MI-Kellogg Eye Center, 1000 Wall Street Room 539, Ann Arbor, MI 48105-0714, USA

DebraThompson Ophthalmology & Biochemistry, University of MI-Kellogg Eye Center, 1000 Wall Street Room 533, Ann Arbor, MI 48105-0714, USA

Gabriel Travis Jules Stein Eye Institute, UCLA School of Medicine, 100 Stein Plaza, Room BH-667, Los Angeles, CA 90095, USA

Donald J. Zack Ophthalmology, Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 809 Maumenee, 600 N.Wolfe Street, Baltimore, MD 21287, USA