title: Evaluation of clearance mechanisms with transscleral drug delivery.
abstract: OBJECTIVE
  The goal of this study was to examine elimination pathways when delivering subconjunctivally administered hydrophilic agents to the retinas of rat eyes.
  
  
  METHODS
  The distribution of sodium fluorescein released from an episcleral implant was compared in live and postmortem eyes. Elimination of the subconjunctivally administered hydrophilic agent IgG through blood and lymphatic vessels was investigated by immunohistochemistry. Additionally, lymphatic elimination of subconjunctivally injected sodium fluorescein was quantitatively evaluated.
  
  
  RESULTS
  NaFl released from an episcleral implant was successfully delivered to the subretinal space in the postmortem eye but failed to do so in the live eye. Immunohistochemical visualization of the conjunctival tissue demonstrated dense distribution of blood and lymphatic vessels while also confirming the elimination of subconjunctivally administered IgG through these same vessels. The lymphatic elimination rate after injection of 75.6 μg of a hydrophilic agent, sodium fluorescein, into the subconjunctival space was determined to be 105 ng/min between 30 and 60 minutes.
  
  
  CONCLUSIONS
  Conjunctival blood and lymphatic vessel elimination considerably limit transscleral hydrophilic drug delivery to the retina.
authors.affiliation: Department of Ophthalmology, College of Medicine, Soonchunhyang University, Seoul, South Korea.
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Weiling
authors.initials: W
authors.lastname: He
authors.forename: Shaun B
authors.initials: SB
authors.lastname: Robinson
authors.forename: Michael R
authors.initials: MR
authors.lastname: Robinson
authors.forename: Karl G
authors.initials: KG
authors.lastname: Csaky
authors.forename: Hyuncheol
authors.initials: H
authors.lastname: Kim
mesh_terms: D000818:Animals; D003228:Conjunctiva / Q000098:blood supply; D016503:Drug Delivery Systems; D004343:Drug Implants; D005260:Female; D019793:Fluorescein / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D065347:Hypromellose Derivatives; D042601:Lymphatic Vessels / Q000378:metabolism; D008747:Methylcellulose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D011956:Receptors, Cell Surface / Q000378:metabolism; D012160:Retina / Q000378:metabolism; D012590:Sclera / Q000378:metabolism*
chemical_list: D004343:Drug Implants; D005456:Fluorescent Dyes; C533408:Lyve1 protein, rat; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011956:Receptors, Cell Surface; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D019793:Fluorescein