title: Enhancement of scleral macromolecular permeability with prostaglandins.
abstract: OBJECTIVE
  It is proposed that the sclera is a metabolically active and pharmacologically responsive tissue. These studies were undertaken to determine whether prostaglandin exposure can enhance scleral permeability to high-molecular-weight substances.
  
  
  METHODS
  Topical prostaglandin F2 alpha (PGF2 alpha) was administered to monkeys to determine if this altered the amount of scleral matrix metalloproteinases (MMPs). Experiments also were performed to determine whether the prostaglandin F (FP) receptor and gene transcripts are expressed in normal human sclera. Permeability of organ-cultured human sclera following prostaglandin exposure then was studied and the amount of MMP released into the medium measured. Finally, the permeability of human sclera to basic fibroblast growth factor (FGF-2) was determined following prostaglandin exposure.
  
  
  RESULTS
  Topical prostaglandin administration that reduced scleral collagen also increased scleral MMP-1, MMP-2, and MMP-3 by 63 +/- 35%, 267 +/- 210%, and 729 +/- 500%, respectively. FP receptor protein was localized in scleral fibroblasts, and FP receptor gene transcript was identified in sclera. Exposure to prostaglandin F2 alpha, 17-phenyltrinor, PGF2 alpha, or latanoprost acid increased scleral permeability by up to 124%, 183%, or 213%, respectively. In these cultures, MMP-1, MMP-2, and MMP-3 were increased by up to 37%, 267%, and 96%, respectively. Finally, transscleral absorption of FGF-2 was increased by up to 126% with scleral exposure to latanoprost.
  
  
  CONCLUSIONS
  These studies demonstrate that the sclera is metabolically active and pharmacologically responsive to prostaglandins. Further, they demonstrate the feasibility of cotreatment with prostaglandin to enhance transscleral delivery of peptides, such as growth factors and high-molecular-weight substances, to the posterior segment of the eye.
authors.affiliation: Glaucoma Center, University of California, San Diego, School of Medicine, La Jolla, USA.
authors.forename: R N
authors.initials: RN
authors.lastname: Weinreb
mesh_terms: D000368:Aged; D000818:Animals; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D000077338:Latanoprost; D008252:Macaca fascicularis; D046911:Macromolecular Substances; D020782:Matrix Metalloproteinases / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012590:Sclera / Q000187:drug effects* / Q000378:metabolism
chemical_list: C092396:17-phenyltrinorprostaglandin E2; D046911:Macromolecular Substances; D011461:Prostaglandins F, Synthetic; D012333:RNA, Messenger; D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor; D016222:Fibroblast Growth Factor 2; C041158:prostaglandin F2 isopropyl ester; D000077338:Latanoprost; D015237:Dinoprost; D020782:Matrix Metalloproteinases; D015232:Dinoprostone