Laboratoire de Physiopathologie Cellulaire et Molculaire de la Rtine, INSERM UMR S592, UPMC Paris 6,

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CDR INSTITUT DE LA VISION UMR 968 INSERM UPMC
7210 CNRS UPMC
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Plan in 2001
An integrated cluster
Clinical Research  Centre dInvestigations
Cliniques  ( PHRC, Phases 1- 3)
Laboratory Research Institut de la Vision
Pharmaceutical industry Applied Research

• Preclinical evaluation
• Clinical evaluation
• Epidemiology
• Genetics
• Clinical trials
• Tele Medicine
• Medical devices
• Imaging
• Lasers

• Molecular Biology
• Cell biology
• Physiology
• Genetics
• Cell therapy
• Gene therapy
• Pharmacology
• .

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Departments and teams
Team 4 (S. Bhattacharya, UCL Chaire
dExcellence) Emerging teams Team 5 ( T.
Léveillard ) Cell therapy, functional genomics (
Pr Don Zack, Johns Hopkins Chaire dExcellence)
Team 1 (A. Chedotal) Molecules regulating axon
guidance Team 2 (O. Goureau) (R.
Kozyraki) Progenitors and stem cells Team 3
Avenir (J. Livet) Inserm recruitment
Team 6 (J. Sahel) Modelling retinal diseases Team
8 (C. Baudouin) Ocular surface disorders and
glaucoma (from U 598) Team 11 (M.
Corral-Debrinski) Gene transfer in Mitochondrial
diseases Platform (V. Borderie) Cell therapy of
the cornea
Team 7 (S. Picaud) Physiology and pharmacology
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Department of Development
Differentiation, axon guidance, migration
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Department of Development
In vivo perturbations of neuronal Development
Homologous Recombination (knock-out, knock-in)
Teams 1, 3, Avenir
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Department of Genetics
Team 4 Study of retinal diseases using genetics
and functional biology Prof. Shomi
Bhattacharya Isabelle Audo/ S. Mohand-Said (CIC)
Genotype-Phenotype correlations Genetics of
age-related macular degeneration. Lipids and
macula Prof. Eric Souied Emerging Teams Retinal
phagocytosis implication of retinal pigment
epithelial cells in photoreceptor function Dr.
Emeline Nandrot Congenital stationary night
blindness and progressive inherited eye
diseases Dr. Christina Zeitz
Team 5 Rod-cone interactions for therapeutic
approaches of blinding diseases Dr. Thierry
Léveillard
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Ophthalmic Genetics PRPF31 mutations in
retinitis pigmentosa patients
Vithana et al., Mol Cell 2001
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Rod-derived Cone Viability Factor
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CLONAGE PAR EXPRESSION
Identification de Gènes Candidats
Purification des plasmides de la banque par
ensemble de 100 clones
Banque dexpression de rétine
Transfection des cellules COS
Récolte des milieux conditionnés
Cultures enrichies en cônes
Cellules vivantes
Cellules mortes
Division des ensembles sélectionnés en
sous-ensembles
Comptage cellulaire
Sélection des ensembles candidats
Facteur(s) trophique(s)
PNAS, 1998 Arch Ophth, 2000 IOVS, 2003 Nature
Genetics 2004
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RdCVF protein increases cone survival and
preserves cone function
RdCVF protein injections
Photopic b-wave amplitude (µV)
B
A
Cone density
C
Photopic ERG
plt0.001
plt0.01
140


120
100
RdCVF
80
0
60
SM
0
0
SM
RdCVF
RdCVF
AAV2.5-RdCVF injection
E
Photopic b-wave amplitude (µV)
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F
Cone density
Photopic ERG
plt0.01

plt0.001
RdCVF
0
0
0
RdCVF
EGFP
EGFP
RdCVF
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Development of standards and information
networking system
DATA ACCESS ANALYSIS STANDARD DEFINITION
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Platform for retinal cell function analysis
Visual acuity
Patch clamp isolated cells, slices
Bic
I4AA
BicI4AA
GABA
in vivo electrophysiology ERG
500pA
1s
Matrix of 60 electrodes ex vivo retina
in vivo imaging
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Retinal prosthesis

• Determination of required resolution
• Optimisation of chips (shape of electrodes,
  coating)
• Mathematical modelling
• Validation in vitro and in vivo
• Clinical trials (Second Sight, IMI,..)

Light
?
Isolated retina
MEA-60
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Département Pathophysiology and Therapy
Team N8 Role of chemokines in the
pathophysiology of the anterior segment of the
eye Resp. Christophe Baudouin

• Driving innovation in currently untreatable
  diseases
• Building upon a strong interaction between
  clinical practice, investigation (CIC) and
  laboratory studies
• Strong emphasis on clinical and pre-clinical
  imaging at the tissular and cellular level
  (Adaptive optics, OCT, HRT,..)
• Improvement or design of novel therapies

Team 11 Gene transfer to the mitochondria
application to optic neuropathies Resp. Marisol
Corral-Debrinski
Team N 6 Math Resp. José-Alain Sahel
Platform Cell therapy of the cornea Resp.
Vincent Borderie
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Innovative imaging technologies
In humans In animal models
Labbe et al. Ophthalmology 2005 2006 Cornea
2006 Sonigo et al. IOVS 2006 Amar et al.
Ophthalmology 2007
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Dpt Pathophysiology Therapy/Dpt Visual
Processing Transversal project Glaucoma
One major blindness disease 70 M people
worldwide. Increase in IOP inducing neuronal cell
degeneration
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Pre-clinical studies Allotopic expression
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Procédé de production du produit de thérapie
cellulaire (PTC)
Base co-culture de kératinocytes avec
fibroblastes murins 3T3 dans milieu de Green
Principe retenu culture de cellules
épithéliales limbiquessur membrane amniotique à
partir dexplants limbiques
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Structural and functional biomarkers
Nusinowitz 1999
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0
2
4
4
Fovea
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Field size 300 µm (diameter) 450 µm from fovea
Cone density
Cones density map (cell/mm² retina)
ONL thickness
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Research from  bench to bedside 

• Photoreceptor degeneration and rescue (see
  transversal project)
• Neuroprotection in Glaucoma (see transversal
  project)
• Visual restauration
• Stem cells (see transversal project)
• Project Retinal Prosthesis
• Biomarkers imaging from mouse to human
• Morphological anterior segment (team 8) retina
  (team 6 and astronomers)
• Functional teams 6, 7 and 10
• Visual impairment and rehabilitation (department
  visual processing and industrial consortium)

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Industrial partnerships

• Ovation Pharmaceuticals and GABARET (ANR) team
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• Collaborative projects Dry Eye, Glaucoma team
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• Cornea teams 8,9
• Biogen Idec team 1
• Melatonin receptors Servier team 7
• Allergan (team 5,6)
• Creation of Fovea pharmaceuticals 2005 50 M
  fund raising (2005-2007)
• Licence Novartis RDCVF (sous licencié à Fovea)
• Project Medicen  retinopathie  Maunakea,
  Imagine Eyes et Fovea spin-off company planned
• Projet ANR  INOVEO  Imagine Eyes and Maunakea
• Clinical trials at the CIC (more than 10
  companies)
• Altran Award Artificial retina ( trials with
  Second Sight, IMI)
• Reference Centre for Novartis (along with
  Harvard, Johns Hopkins,..)

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Companies within the Institute Building

• PHARMA and NUTRACEUTIQUE 4 companies
• Visual Impairment 3 companies
• CRO 1 entity
• Shared platforms / major participation to the
  cost of the building rental
• Number of jobs 100
• Potential for creating two new companies in 08-09

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POLE HANDICAP INSTITUT de la VISION

• DESCARTES
• Développement de lunettes électroniques pour
  compenser les déficiences visuelles grâce à
  lutilisation du savoir dEssilor dans les
  lunettes vidéos et la réalité augmentée
• Développement de cannes blanches électroniques
  avec intégration dun GPS à central inertiel
  grâce au savoir faire de Visiotact
• ROMEO
• Développement dun robot dassistance à domicile
  pour les malvoyants grâce au savoir dAldebaran,
  du CEA et de beaucoup de PME françaises.
• APPARTEMENT INTELLIGENT
• Dossier en cours de montage pour améliorer
  lautonomie à domicile des malvoyants
• PANAMMES
• Zone dexpérimentation urbaine pour tester des
  nouveaux services pour malvoyants et
  malentendants

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Low VISION Technologies

• Plan for creation of two joint laboratories
• neuro-psycho-physics of Visual impairment
• Photobiology

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MERCI