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PolExGene 12-MONTH-MEETING Helsinki

PolExGene 12-MONTH-MEETING Helsinki. Biocompatible non-viral polymeric gene delivery systems for the ex vivo treatment of ocular and cardiovascular diseases with high unmet medical need. Eberhart Zrenner Ulrich Schraermeyer Edda Fahl Sylvie Julien Tobias Peters.

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PolExGene 12-MONTH-MEETING Helsinki

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  1. PolExGene 12-MONTH-MEETING Helsinki Biocompatible non-viral polymeric gene delivery systems for the ex vivo treatment of ocular and cardiovascular diseases with high unmet medical need Eberhart Zrenner Ulrich Schraermeyer Edda Fahl Sylvie Julien Tobias Peters PolExGene Meeting Helsinki 23.-24. August 2007

  2. The Tübingen Contributions • WP 6.2:In vivo immunological properties of polyplexes and polymer membranes (6 month) • Ocular biomicroscopy and electrophysiology • WP 7.1: Implantation of polymer membranes for ocular diseases (30 month) • Eye-surgery • Ophthalmoscopy (biocompatibility) • Electroretinography • Histological investigations PolExGene Meeting Helsinki 23.-24. August 2007

  3. Expected products • 1. PI + non-degradable polymers • 2. PI + gelatine • 3. PI + gelatine + polymer • First in rats - in regard to the recommended size of polymers • Second tbd • Sterilization – Radiation? EO? PolExGene Meeting Helsinki 23.-24. August 2007

  4. Planning First Implantations • 3 different polymers • 1 rat strain (wt) • 1 mouse strain (wt) • Implantation of first 3 polymers for an observation period of 12 weeks • Alternative: first 3 polymers for an observation period of 4 weeks PolExGene Meeting Helsinki 23.-24. August 2007

  5. Study plan - overview • 5C57BL/6 wt-mice alternative4Wistar wt-rats • Three independent implantations of three different polymer complexes • Time course of analysis: 12 weeks Results: 5 months after implantation PolExGene Meeting Helsinki 23.-24. August 2007

  6. Implantation of polymer complex • Before implantation, sterilization of the membrane by radiation (25 Gy), done by Ghent group. • Subretinal implantation of the polymer complex: • anaesthesia, • lateral sclerotomy, • detachment of the retina and insertion of the polymer complex funduscopically controlled. • SLO examination PolExGene Meeting Helsinki 23.-24. August 2007

  7. Subretinal surgery PolExGene Meeting Helsinki 23.-24. August 2007

  8. Surgery PolExGene Meeting Helsinki 23.-24. August 2007

  9. Electroretinography (ERG) PolExGene Meeting Helsinki 23.-24. August 2007

  10. (Seeliger et al., Vision Res 05) Scanning - laser ophthalmoscopy (SLO) PolExGene Meeting Helsinki 23.-24. August 2007

  11. Histology • Enucleation • Fixation • Embedded in Epon resin (to discuss) • The membranes will be sectioned at the same time (to discuss) • Half of the eyes will be embedded in paraffin → Immunological investigations. PolExGene Meeting Helsinki 23.-24. August 2007

  12. Immunohistochemistry • Enucleation • Fixation in formalin • Embed in paraffin wax, cut to 5 mm sections and de-paraffinise (to discuss) • Staining with haematoxylin and eosin to locate the areas of interest • Detection of immunoreactivity with: • anti-macrophages antibody • anti-vimentin antibody to evaluate possible gliosis and other cellular reactions induced by the subretinal implant PolExGene Meeting Helsinki 23.-24. August 2007

  13. Pathophysiology in the RCS-Rat Mutation of Receptor-Tyrosinkinase-Gene Mertk ONL 7 weeks 5 weeks 3 weeks Decrease in ERG response PolExGene Meeting Helsinki 23.-24. August 2007

  14. Study plan - overview • 5C57BL/6 wt-mice alternative4Wistar wt-rats • Three independent implantations of three different polymer complexes • Time course of analysis: 12 weeks Results: 5 months after implantation PolExGene Meeting Helsinki 23.-24. August 2007

  15. Thank you… …time for discussion PolExGene Meeting Helsinki 23.-24. August 2007

  16. Additional information PolExGene Meeting Helsinki 23.-24. August 2007

  17. Fluorescein leakage in retinal neovascularisation ICG imaging of subretinal membranes Scanning laser ophthalmoscopy (SLO) PolExGene Meeting Helsinki 23.-24. August 2007

  18. XLRS Patient IR Rs1h -/Ymouse PNAS 2002; 99:6222-7 IR IR Rs1h-/y model of x-linked juvenile retinoschisis PolExGene Meeting Helsinki 23.-24. August 2007

  19. Persistent vitreous vessels P14 P21 Pathophysiology in the Norrie mouse model PolExGene Meeting Helsinki 23.-24. August 2007

  20. Developmental vascular pattern wt P14 P38 Pathophysiology in the Norrie mouse model wt PolExGene Meeting Helsinki 23.-24. August 2007

  21. Pathophysiology in the Norrie mouse model PolExGene Meeting Helsinki 23.-24. August 2007

  22. Study plan - alternative 1 • 5C57BL/6 wt-mice alternative4Wistar wt-rats • Three independent implantations of three different polymer complexes • Time course of analysis: 4 weeks Results: 3.5 months after implantation PolExGene Meeting Helsinki 23.-24. August 2007

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