title: Scleral permeability varies by mouse strain and is decreased by chronic experimental glaucoma.
abstract: OBJECTIVE
  To determine differences in scleral permeability, as measured by diffusion of macromolecules, by using fluorescence recovery after photobleaching (FRAP), with reference to differences by mouse strain, scleral region, and the effect of experimental glaucoma.
  
  
  METHODS
  In three mouse strains (B6, CD1, and B6 mice with mutation in collagen 8α2 [Aca23]), we used FRAP to measure the diffusion of fluorescein isothiocyanate-dextran, molecular weight 40 kDa, into a photobleached zone of sclera. Scleral regions near the optic nerve head (peripapillary) and two successively more anterior regions were compared. Sclera from mouse eyes subjected to chronically elevated intraocular pressure after bead injection into the anterior chamber were compared to fellow eye controls. FRAP data were compared against estimated retinal ganglion cell axon loss in glaucomatous eyes.
  
  
  RESULTS
  Diffusion rates of dextran molecules in the sclera were significantly greater in Aca23 and B6 mice than in CD1 mice in a multivariate model adjusted for region and axial length (P < 0.0001). Dextran diffusion significantly decreased in glaucomatous eyes, and the decline increased with greater axon loss (P = 0.0003, multivariable model). Peripapillary scleral permeability was higher in CD1 than B6 and Aca23 mice (P < 0.05, multivariable model, adjusted by Bonferroni).
  
  
  CONCLUSIONS
  Measurement of the diffusion rates of dextran molecules in the sclera showed that glaucoma leads to decreased scleral permeability in all three mouse strains tested. Among mouse strains tested, those that were more susceptible to glaucomatous loss of retinal ganglion cells had a lower scleral permeability at baseline.
authors.affiliation: Glaucoma Center of Excellence and Center for Nanomedicine, Wilmer Ophthalmological Institute, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Pease
authors.forename: Ericka N
authors.initials: EN
authors.lastname: Oglesby
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Cone-Kimball
authors.forename: Joan L
authors.initials: JL
authors.lastname: Jefferys
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Steinhart
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Kim
authors.forename: Justin
authors.initials: J
authors.lastname: Hanes
authors.forename: Harry A
authors.initials: HA
authors.lastname: Quigley
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003911:Dextrans / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D005901:Glaucoma / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010539:Permeability; D012590:Sclera / Q000378:metabolism*
chemical_list: D003911:Dextrans
keywords: dextran; diffusion; experimental model; glaucoma; mouse; permeability; photobleaching; sclera