Yvan Arsenijevic – FAA
Fondation Asile des Aveugles, Lausanne, Switzerland


Institute description
The Unit of Gene Therapy and Stem Cell Biology is situated in the area of the “Asile des Aveugles” and belongs to the academic Ophthalmology Service of the University of Lausanne, in the Jules-Gonin Eye Hospital, Switzerland. The centre is internationally recognized in Ophthalmology for retina surgery, tumour treatment (melanoma and retinoblastoma) as well as for patient genotyping. The reputation of the hospital resulted in the creation of the renowned club Gonin, which gathers world experts of the retina year by year. Two conventions were signed with the University of Tunis as well as the University of Alger to promote patients, trainees, and scientific exchanges, the main interest being recessive orphan diseases. Collaboration with the Swiss Federal Institute of Technology-Lausanne and the Paul Scherer Institute offers access to a wide panel of technologies and knowledge that already guarantee fruitful collaborations and therapies.

Group leader
After having studied neural stem cells for several years, Yvan Arsenijevic moved to ophthalmology and participated with the precursors in the field to the isolation and the description of retinal stem cells. His background in neuroscience proved to be a great advantage in the comprehension of the complex network of the retina and his stem cell approach in the factors contributing to cell survival or cell death.

The experience of the Unit in gene replacement is illustrated by several studies using lentiviral vectors. First, Dr Arsenijevic’s group contributed to the characterization of lentivirus-mediated gene transfer in mouse retinas. They also demonstrated the limitation of such a vector to efficiently target photoreceptors due to a physical barrier that can be partially bypassed using enzymes. The group has also experience with neuroprotective approaches to gene therapy. Furthermore, they demonstrated the protective effect of Rpe65 gene transfer and function restoration on cone photoreceptors in an animal model of Leber Congenital Amaurosis (LCA, Rpe65 -/- mice). Mouse phenotyping was further developed: Retcam for eye fundus, pupillometry, and various behavioural tests. Moreover, a close collaboration with Prof. Munier from the Jules-Gonin Eye Hospital was built in order to identify patients suffering from mutations in the Rpe65 gene that could benefit in the future from a gene replacement therapy. With the same rationale, genotyping of patients suffering from LCA was recently initiated in Switzerland and encouraged by the Retina Swiss Association (www.retina.ch). Finally, fundamental studies on retina degeneration lead Dr Arsenijevic’s group to reveal that the homeodomain Bmi1 is a key actor in the rd1 mouse pathology.

Role in the project
Workpackage Leader for WP3. His laboratory is also involved in WP1, WP2 and WP4. In particular, his research group will be focused on the: i. Characterization of PDE6B regulatory regions (WP1); ii. Coevaluation of gene replacement (WP2); iii. Evaluation of combined strategy with Bmi1 inhibition (WP3), and iv. Identification and phenotyping of PDE6B and AIPL1 patients in Switzerland (WP4), in collaboration with Prof. Munier (Jules-Gonin Eye Hospital) and Prof. Schorderet (Institut de Recherche en Ophtalmologie, Sion, CH).

Key personnel

Name Title Gender Role/Expertise
Yvan Arsenijevic Group leader M WPL for WP3
Corinne Kostic Investigator F Gene transfer, gene therapy evaluation
Dusan Zencak PhD Student M Dissection of Bmi1 action on degenerating retina
Anna Maillard Technician F Histological analysis
Meriem Tekaya Technician F Injections, functional and histological analysis
Vérène Pignat Technician F Injections, functional and histological analysis
Dana Wanner Technician F Molecular biology
Alexey Matskevich Post-doc Fellow M WP3
Jonas Cicenas Post-doc Fellow M WP1, WP3

Key publications

Bemelmans AP, Kostic C, Crippa SV, Hauswirth WW, Lem J, Munier FL, Seeliger MW, Wenzel A and Arsenijevic Y (2006). Lentiviral-mediated transfer of the RPE65 cDNA rescues both survival and function of cone photoreceptors in a mouse model of Leber Congenital Amaurosis. PLoS Med 3: e347.

Gruter O, Kostic C, Perez MTR, Zografos L, Munier FL, Schorderet DF and Arsenijevic Y (2005). Lentiviral vector-mediated gene transfer in adult mouse photoreceptors is impaired by a physical barrier. Gene Ther 12: 942-947.

Zencak D, Lingbeek M, Kostic C, Tekaya M, Tanger E, Hornfeld D, Jaquet M, Munier FL, Schorderet DF, van Lohuizen M, Arsenijevic Y (2005). Bmi1 loss produces an increase in astroglial cells and a decrease in neural stem cell population and proliferation. J Neurosci 25: 5774-5783.

Kostic C, Chiodini F, Salmon P, Wiznerowicz M, Deglon N, Hornfeld D, Trono T, Aebischer P, Schorderet DF, Munier FL, Arsenijevic Y (2003). Activity analysis of housekeeping promoters using self-inactivating lentiviral vector delivery into the mouse retina. Gene Ther 10: 818-821.

Van Adel BA, Kostic C, Deglon N, Ball AK, Arsenijevic Y (2003). Delivery of Ciliary neurotrophic factor via lentiviral-mediated transfer protects rapidly axotomized retinal ganglion cells for an extended period of time. Hum Gene Ther 14: 103-115.