title: Thrombospondin-1 (TSP1)-null and TSP2-null mice exhibit lower intraocular pressures.
abstract: OBJECTIVE
  Thrombospondin-1 (TSP1) and TSP2 are matricellular proteins that have been shown to regulate cytoskeleton, cell adhesion, and extracellular matrix remodeling. Both TSP1 and TSP2 are found in the trabecular meshwork (TM). In cadaver eyes with primary open-angle glaucoma (POAG), TSP1 is increased in one third of patients. We hypothesized that TSP1 and TSP2 participate in the regulation of intraocular pressure (IOP). Methods. IOPs of TSP1-null, TSP2-null mice, and their corresponding wild-type (WT) mice were measured using a commercial rebound tonometer. Fluorophotometric measurements assessed aqueous turnover. Central corneal thickness (CCT) was measured by optical coherence tomography. Iridocorneal angles were examined using light microscopy (LM), immunofluorescence (IF), and transmission electron microscopy (TEM).
  
  
  RESULTS
  Average IOPs of TSP1-null and TSP2-null mice were 10% and 7% less than that of the corresponding WT mice, respectively. CCTs were 6.5% less in TSP1-null mice (P < 0.05) and 1.1% less in TSP2-null mice (P > 0.05). Fluorophotometric measurements suggest that aqueous turnover rates in TSP1-null and TSP2-null mice are greater than those of WT mice. LM of the TSP1-null and TSP2-null iridocorneal angles reveals morphology, which is indistinguishable from that of their corresponding WTs. IF revealed possible concurrent underexpression of TSP2 in TSP1-null mice and of TSP1 in TSP2-null mice. TEM revealed larger collagen fibril diameters in TSP1-null and TSP2-null mice compared with WTs.
  
  
  CONCLUSIONS
  TSP1-null and TSP2-null mice have lower IOPs than their WT counterparts. The rate of aqueous turnover suggests that the mechanism is enhanced outflow facility. An alteration in the extracellular matrix may contribute to this finding.
authors.affiliation: Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, 243 Charles Street, Boston, MA 02114, USA.
authors.forename: Ramez I
authors.initials: RI
authors.lastname: Haddadin
authors.forename: Dong-Jin
authors.initials: DJ
authors.lastname: Oh
authors.forename: Min Hyung
authors.initials: MH
authors.lastname: Kang
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Villarreal
authors.forename: Ja-Heon
authors.initials: JH
authors.lastname: Kang
authors.forename: Rui
authors.initials: R
authors.lastname: Jin
authors.forename: Haiyan
authors.initials: H
authors.lastname: Gong
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Rhee
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D004195:Disease Models, Animal; D004728:Endothelium, Corneal / Q000378:metabolism / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000378:metabolism; D015590:Fluorophotometry; D005786:Gene Expression Regulation; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D015151:Immunoblotting; D007429:Intraocular Pressure / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D012313:RNA / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019700:Thrombospondin 1 / Q000096:biosynthesis / Q000235:genetics*; D019699:Thrombospondins / Q000096:biosynthesis / Q000235:genetics*; D041623:Tomography, Optical Coherence; D014129:Trabecular Meshwork / Q000378:metabolism / Q000648:ultrastructure; D000099262:Thrombospondin 2
chemical_list: D015815:Cell Adhesion Molecules; D012313:RNA; D019700:Thrombospondin 1; D019699:Thrombospondins; D000099262:Thrombospondin 2