title: Ballistic CTLA4 and IL-4 gene transfer into the lower lid prolongs orthotopic corneal graft survival in mice.
abstract: OBJECTIVE
  To explore outflow from the eye and to determine and modulate the influence of lymphatic drainage on corneal graft survival in mice.
  
  
  METHODS
  Tracer experiments were conducted in BALB/c mice using the (99m)Tc colloidal albumin Nanocoll. Count rates were determined in the eyes, submandibular lymph nodes, spleen, liver and blood 24 h after subconjunctival, intracorneal, intracameral (anterior chamber), intravenous and subcutaneous lower-lid or upper-lid injections ( n=6 each). Four groups of BALB/c mice ( n=8) received corneal transplants from C3H mice; two of them were treated ballistically with vector CTLA4+IL-4 onto the leg or the lower lid, one group was untreated and the other control group was treated with an empty minimalistic, immunologically defined, gene expression (MIDGE) vector.
  
  
  RESULTS
  Radioactivity was detected in the liver, spleen and ipsilateral submandibular lymph node after intracameral injection as follows: 91.9%, 6.6% and 1.2% respectively. Radioactivity uptake of the ipsilateral submandibular lymph node was also low after intravenous injection (0.1%) but high after intracorneal (33.8%), lower-lid (62.0%) and subconjunctival (71.2%) injection. Vector CTLA4+IL-4 treatment of the lower lid but not of the leg prolonged graft survival ( P=0.004).
  
  
  CONCLUSIONS
  These tracer studies confirmed for the first time identical lymphatic drainage from the cornea and the lower lid. Logically, lymphatic drainage could be manipulated and graft survival improved by gene transfer to the lower lid.
authors.affiliation: Department of Ophthalmology, University Hospital Benjamin Franklin, Free University of Berlin, Hindenburgdamm 30, 12203, Berlin, Germany.
authors.forename: Er-Ping
authors.initials: EP
authors.lastname: Zhang
authors.forename: Jürgen
authors.initials: J
authors.lastname: Franke
authors.forename: Matthias
authors.initials: M
authors.lastname: Schroff
authors.forename: Claas
authors.initials: C
authors.lastname: Junghans
authors.forename: Burghardt
authors.initials: B
authors.lastname: Wittig
authors.forename: Friedrich
authors.initials: F
authors.lastname: Hoffmann
mesh_terms: D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D019470:Biolistics; D060908:CTLA-4 Antigen; D016039:Corneal Transplantation; D005143:Eyelids; D005260:Female; D005822:Genetic Vectors; D006085:Graft Survival; D006614:Hindlimb; D007267:Injections; D015847:Interleukin-4 / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D013154:Spleen / Q000378:metabolism; D013363:Submandibular Gland; D013668:Technetium Tc 99m Aggregated Albumin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014184:Transplantation, Homologous
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D013668:Technetium Tc 99m Aggregated Albumin; C083602:technetium Tc 99m nanocolloid; D015847:Interleukin-4