title: Diffusion of macromolecules through sclera.
abstract: OBJECTIVE
  To quantify the in vitro permeability coefficient over different topographical locations of porcine sclera to macromolecules with different molecular weight.
  
  
  METHODS
  Fresh equatorial and posterior superotemporal porcine sclera was mounted in a two-chamber diffusion apparatus, and its permeability to fluorescein isothiocyanate (FITC)-conjugated dextrans ranging in molecular weight from 40 kDa to 150 kDa was determined by fluorescence spectrophotometry. The sclera was processed as frozen sections and viewed with a fluorescence microscope. The thickness of the area and the thickness that macromolecules enriched in the surface of sclera were measured.
  
  
  RESULTS
  The permeability coefficient (Pc) of porcine sclera to macromolecules was significantly higher (40 kDa, p = 0.028; 70 kDa, p = 0.033; 150 kDa, p = 0.007) in equatorial region than posterior, which could be attributed to the significant difference of thickness (p < 0.001, Kruskal-Wallis) between them. Moreover, linear regression indicated a significant negative relationship (40 kDa, p < 0.001; 70 kDa, p = 0.015; 150 kDa, p < 0.001) between scleral permeability coefficient and thickness. Also, Pc declined significantly with increasing molecular weight (MW, p < 0.001, Kruskal-Wallis). The area that the macromolecules enriched in the scleral surface was thicker for those with larger MW (p < 0.001, Kruskal-Wallis). The maximum MW and size for equatorial and posterior superotemporal scleral tissue were 185.01 KDa and 180.42 KDa, 9.92 nm and 9.67 nm, respectively.
  
  
  CONCLUSIONS
  The permeability coefficient of porcine sclera has a significant negative relationship with scleral thickness and MW of macromolecules. Larger macromolecules are more likely to accumulate in scleral surface. The difference between topographical locations may have pharmacokinetic implications when considering transscleral diffusion of macromolecules.
authors.affiliation: Department of Ophthalmology, People's Hospital, Peking University, Beijing, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Miao
authors.forename: Bi-Dong
authors.initials: BD
authors.lastname: Wu
authors.forename: Yong
authors.initials: Y
authors.lastname: Tao
authors.forename: Xiao-Xin
authors.initials: XX
authors.lastname: Li
mesh_terms: D000818:Animals; D001692:Biological Transport; D003911:Dextrans / Q000493:pharmacokinetics*; D015194:Diffusion Chambers, Culture; D055459:Facilitated Diffusion; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D046911:Macromolecular Substances / Q000493:pharmacokinetics*; D008856:Microscopy, Fluorescence; D008970:Molecular Weight; D010539:Permeability; D012590:Sclera / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013552:Swine
chemical_list: D003911:Dextrans; D046911:Macromolecular Substances; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate