Influence of molecular weight on intracameral dextran movement to the posterior segment of the mouse eye.
OBJECTIVE
Uveoscleral outflow provides a potential pathway to the posterior segment for drug delivery. In this study, the influence of molecular weight on the intraocular distribution of dextran molecules after intracameral injection in the mouse eye was investigated.


METHODS
The anterior chambers of the eyes of 64 anesthetized NIH Swiss mice were perfused with various fluorescent dextran solutions (10, 40, 70, and 500 kDa) at 500 nL/min for 10 minutes. At 10, 20, or 60 minutes after the initiation of the anterior chamber perfusion, the mice were killed and tissue obtained for evaluation by fluorescence microscopy.


RESULTS
Each of the different molecular weight dextrans were visible in the anterior chamber of the mouse eye after the termination of the experiments. The 10-kDa dextran was observed in the supraciliary space and the supraciliary sclera after 10 minutes and in the anterior sclera after 60 minutes of perfusion. The 40-kDa dextran was detected in the supraciliary space and the anterior sclera after 10 minutes and in the anterior choroid and sclera after 20 and 60 minutes, but not in the posterior segment. The 70-kDa dextran was observed in the supraciliary space and anterior choroid after 10 minutes. After 20 minutes, it was visible in the equatorial choroid. After 60 minutes, it was observed in the posterior choroid. The 500-kDa dextran was observed in the supraciliary space and the anterior choroid after 10 minutes and in the supraciliary sclera at 20 minutes. At 60 minutes, 500-kDa dextran was observed in the equatorial choroid, but not farther toward the posterior.


CONCLUSIONS
The influence of molecular weight on the redistribution of macromolecules from the anterior chamber to the posterior globe in the mouse eye appears to be similar to primate eyes. These similarities include passage of all size dextrans through the proximal uveoscleral pathway, the dependence of the extent of posterior movement on the size of the dextran, and the absence of large dextran entry into the distal uveoscleral pathway.
Bernd
Antje S
AS
Hamilton Glaucoma Center and Department of Ophthalmology, University of California San Diego, La Jolla, California 92093, USA.
Aihara
Makoto
M
Lindsey
James D
JD
Weinreb
Robert N
RN
D000818:Animals; D000867:Anterior Chamber / Q000378:metabolism*; D003911:Dextrans / Q000493:pharmacokinetics*; D005452:Fluoresceins / Q000493:pharmacokinetics*; D051379:Mice; D008856:Microscopy, Fluorescence; D008970:Molecular Weight; D012590:Sclera / Q000378:metabolism*; D014129:Trabecular Meshwork / Q000378:metabolism*; D014602:Uvea / Q000378:metabolism*
D003911:Dextrans; D005452:Fluoresceins; C052526:fluorescein-dextran