Institute description
Founded in 1826, UCL was the first English university established after Oxford and Cambridge, the first to admit students regardless of race, class, religion or gender, and the first to provide systematic teaching of law, architecture and medicine. UCL Institute of Ophthalmology is one of a number of specialized research centres linked to University College London and is, together with Moorfields Eye Hospital, one of the leading centres for eye research. The Institute is committed to a multi-disciplinary research portfolio that furthers an understanding of the eye and visual system linked with clinical investigations targeted to specific problems in the prevention and treatment of eye disease. The combination of the Institute’s research resource with the resources of Moorfields Eye Hospital, which has the largest ophthalmic patient population in the Western World, opens the way for advances at the fore-front of vision research.

Group leader
Robin Ali is Professor of Human Molecular Genetics and Head of the Division of Molecular Therapy at UCL Institute of Ophthalmology.

The main interest of Prof. Ali’s laboratory is the development of novel therapies for retinal disorders with a major emphasis on translating research into clinical applications. Over the past 13 years, Prof. Ali’s laboratory has been optimizing adeno-associated virus (AAV) or lentivirus gene transfer to the eye to develop gene therapy for eye disease and in particular for disorders affecting the retina, including inherited retinal degeneration as well as complex diseases such as those associated with retinal and choroidal neovascularization and posterior uveitis.

A major aspect of Prof. Ali’s research is the development and use of a wide variety of genetic and experimental animal models of retinal disorders, including large animal models, in order to assess novel therapeutic approaches. The group has established a broad programme of work to demonstrate proof-of-concept for a number of alternative strategies, including gene replacement therapy and/or delivery of siRNA to treat animal models of inherited retinal degeneration and delivery of genes encoding angiostatic, antiapoptotic, immunomodulatory or neurotrophic molecules to treat a variety of animal models.

Role in the project
Workpackage Leader for WP2 and WP4. His laboratory is also involved in WP1 and WP3. In particular, his laboratory will be engaged in the: i. Assessment of gene expression in primates (WP1); ii. Evaluation of gene replacement therapy in animal models of PDE6B and AIPL1 deficiency (WP2); iii. Evaluation of combined GDNF and gene replacement therapy in animal models of PDE6b and AIPL1 deficiency (WP3), and iv. Identification and phenotyping of Pde6b and AIPL1 patients in London (WP4).

Key personnel

Key publications

Buch PK, MacLaren RE, Durán Y, Balaggan KS, MacNeil A, Schlichtenbrede FC, Smith AJ, Ali RR (2006). In contrast to AAV-mediated CNTF expression, AAV-mediated expression of GDNF enhances gene replacement therapy in rodent models of retinal degeneration. Mol Ther 14: 700-709.

Pawlyk BS, Smith AJ, Buch PK, Adamian M, Hong D, Sandberg MA, Ali RR, Li T (2005). Gene Replacement Therapy Rescues Photoreceptor Degeneration in a Murine Model of Leber Congenital Amaurosis Lacking RPGRIP. Invest Ophthalmol Vis Sci 46: 3039-3045.

Bainbridge JWB, Mistry A, Schlichtenbrede F, Smith A, Broderick C, De Alwis M, Georgiardis A, Taylor PM, Squires M, Sethi C, Charteris D, Thrasher AJ, Sargan D, Ali RR (2003). Stable rAAVmediated transduction of rod and cone photoreceptors in the canine retina. Gene Ther 10: 1336-1344.

Smith AJ, Schlichtenbrede FC, Tschernutter M, Bainbridge JW, Thrasher AJ, Ali RR (2003). AAVmediated gene transfer slows photoreceptor loss in the RCS rat model of retinitis pigmentosa. Mol Ther 8: 118-195.

Ali RR, Sarra G, Stephens C, de Alwis M, Bainbridge JWB, Munro PM, Fauser S, Reichel MB, Kinnon C, Hunt DM, Bhattacharya SS, Thrasher AJ (2000). Restoration of photoreceptor ultrastructure and function in retinal degeneration slow mice by gene therapy. Nat Genet 25: 306-310.