title: The influence of intraocular pressure on the transscleral diffusion of high-molecular-weight compounds.
abstract: OBJECTIVE
  To evaluate the effects of intraocular pressure on the permeability of the human sclera to high-molecular-weight compounds.
  
  
  METHODS
  Human transscleral permeability to FITC-albumin (70 kDa) and 70-kDa and 150-kDa FITC-dextran was determined at transscleral pressures from 0 to 60 mm Hg. For each compound at each pressure, six to eight experiments were performed. Scleral sections were mounted in a two-compartment perfusion chamber. Temperature was maintained at 37 degrees C. Fractions of choroidal perfusate were collected, and fluorescence was measured with a spectrofluorometer. From these data, scleral permeability K(trans) (in centimeters per second) was calculated.
  
  
  RESULTS
  Permeability to FITC-albumin was decreased by approximately one half when pressure was elevated from 0 to 30 mm Hg (P < 0.05). No significant differences in permeability to 70-kDa FITC-dextran were observed at pressures from 0 to 60 mm Hg. Permeability to 150-kDa FITC-dextran decreased by a little more than one half when transscleral pressure was raised from 0 to 15 mm Hg and was approximately 10 times lower at 60 mm Hg than at 0 mm Hg (P < 0.01).
  
  
  CONCLUSIONS
  Human sclera was permeable to compounds with a molecular weight of up to 150 kDa at transscleral pressures ranging from 0 to 60 mm Hg. Transscleral diffusion was relatively unaffected by the pressure gradient, although for 150-kDa FITC-dextran at 60 mm Hg a 10-fold decrease was observed compared with that at 0 mm Hg. These experiments suggest that high-molecular-weight compounds (e.g., immunoglobulins and oligonucleotides) could be effectively delivered transsclerally to the intraocular tissues under circumstances of physiological or elevated intraocular pressure.
authors.affiliation: Department of Ophthalmology, Emory University, Atlanta, GA 30322, USA.
authors.forename: Lars P J
authors.initials: LP
authors.lastname: Cruysberg
authors.forename: Rudy M M A
authors.initials: RM
authors.lastname: Nuijts
authors.forename: Dayle H
authors.initials: DH
authors.lastname: Geroski
authors.forename: Jake A
authors.initials: JA
authors.lastname: Gilbert
authors.forename: Fred
authors.initials: F
authors.lastname: Hendrikse
authors.forename: Henry F
authors.initials: HF
authors.lastname: Edelhauser
mesh_terms: D003911:Dextrans / Q000493:pharmacokinetics*; D004058:Diffusion; D015194:Diffusion Chambers, Culture; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D007429:Intraocular Pressure / Q000502:physiology*; D008875:Middle Aged; D008970:Molecular Weight; D010539:Permeability; D012590:Sclera / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000493:pharmacokinetics*; D013050:Spectrometry, Fluorescence
chemical_list: D003911:Dextrans; C039217:fluorescein isothiocyanate bovine serum albumin; C015219:fluorescein isothiocyanate dextran; D012710:Serum Albumin, Bovine; D016650:Fluorescein-5-isothiocyanate