Diffusion of high molecular weight compounds through sclera.
OBJECTIVE
To determine the in vitro permeability of the sclera to high molecular weight compounds and the relationship between scleral permeability and molecular size.


METHODS
Fresh rabbit sclera was mounted in a two-chamber diffusion apparatus, and its permeability to sodium fluorescein, fluorescein isothiocyanate (FITC)-conjugated bovine serum albumin, FITC-IgG, and FITC dextrans ranging in molecular weight from 4 to 150 kDa was determined by fluorescence spectrophotometry. Electron microscopy was used to assess the impact of the experimental design on scleral ultrastructural integrity. The effect of the diffusion apparatus on scleral hydration was examined. Rabbit scleral permeability was compared with previously reported data for human and bovine sclera.


RESULTS
Scleral permeability decreased with increasing molecular weight and molecular radius, consistent with previous human and bovine data. Molecular radius was a better predictor of scleral permeability than molecular weight. The sclera was more permeable to globular proteins than to linear dextrans of similar molecular weight. The experimental apparatus did not alter scleral ultrastructure. Permeability of rabbit sclera was similar to human sclera but greater than bovine sclera.


CONCLUSIONS
Large molecules, such as IgG, diffuse across sclera in a manner consistent with porous diffusion through a fiber matrix. Transscleral delivery of immunoglobulins and other large compounds to the choroid and retina may be feasible.
Ambati
J
J
Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston 02114, USA.
Canakis
C S
CS
Miller
J W
JW
Gragoudas
E S
ES
Edwards
A
A
Weissgold
D J
DJ
Kim
I
I
Delori
F C
FC
Adamis
A P
AP
D000818:Animals; D003094:Collagen / Q000648:ultrastructure; D003911:Dextrans / Q000493:pharmacokinetics*; D015194:Diffusion Chambers, Culture; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D007074:Immunoglobulin G / Q000494:pharmacology*; D008970:Molecular Weight; D010539:Permeability; D011817:Rabbits; D012590:Sclera / Q000378:metabolism* / Q000648:ultrastructure; D012710:Serum Albumin, Bovine / Q000493:pharmacokinetics*; D013050:Spectrometry, Fluorescence
D003911:Dextrans; D007074:Immunoglobulin G; C039217:fluorescein isothiocyanate bovine serum albumin; C015219:fluorescein isothiocyanate dextran; D012710:Serum Albumin, Bovine; D003094:Collagen; D016650:Fluorescein-5-isothiocyanate