title: The effect of TIMP-1 on the cone mosaic in the retina of the rat model of retinitis pigmentosa.
abstract: OBJECTIVE
  The array of photoreceptors found in normal retinas provides uniform and regular sampling of the visual space. In contrast, cones in retinas of the S334ter-line-3 rat model for RP migrate to form a mosaic of rings, leaving large holes with few or no photoreceptors. Similar mosaics appear in human patients with other forms of retinal dystrophy. In the current study, we aimed to investigate the effect of tissue inhibitor of metalloproteinase-1 (TIMP-1) on the mosaic of cones in S334ter-line-3 rat retinas. We focused on TIMP-1 because it is one of the regulators of the extracellular matrix important for cellular migration.
  
  
  METHODS
  Immunohistochemistry was performed to reveal M-opsin cone cells (M-cone) and the results were quantified to test statistically whether or not TIMP-1 restores the mosaics to normal. In particular, the tests focused on the Voronoi and nearest-neighbor distance analyses.
  
  
  RESULTS
  Our tests indicated that TIMP-1 led to significant disruption of the M-opsin cone rings in S334ter-line-3 rat retinas and resulted in almost complete homogeneous mosaics. In addition, TIMP-1 induced the M-cone spatial distribution to become closer to random with decreased regularity in S334ter-line-3 rat retinas.
  
  
  CONCLUSIONS
  These findings confirm that TIMP-1 induced M-cone mosaics in S334ter-line-3 to gain homogeneity without reaching the degree of regularity seen in normal retinal mosaics. Even if TIMP-1 fails to promote regularity, the effects of this drug on homogeneity appear to be so dramatic that TIMP-1 may be a potential therapeutic agent. TIMP-1 improves sampling of the visual field simply by causing homogeneity.
authors.affiliation: Neuroscience Graduate Program, University of Southern California, Los Angeles, California, United States Center for Vision Science and Technology, University of Southern California, Los Angeles, California, United States.
authors.forename: Yerina
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Neuroscience Graduate Program, University of Southern California, Los Angeles, California, United States Center for Vision Science and Technology, University of Southern California, Los Angeles, California, United States.
authors.forename: Wan-Qing
authors.initials: WQ
authors.lastname: Yu
authors.affiliation: Department of Biomedical Engineering, University of Southern California, Los Angeles, California, United States.
authors.forename: Yun Sung
authors.initials: YS
authors.lastname: Eom
authors.affiliation: Department of Biomedical Engineering, University of Southern California, Los Angeles, California, United States.
authors.forename: Farouk
authors.initials: F
authors.lastname: Bruce
authors.affiliation: Neuroscience Graduate Program, University of Southern California, Los Angeles, California, United States Mary D. Allen Laboratory for Vision Research, Keck School of Medicine of the University of Southern California, USC Eye Institute, Los Angeles, California, United States.
authors.forename: Cheryl Mae
authors.initials: CM
authors.lastname: Craft
authors.affiliation: Neuroscience Graduate Program, University of Southern California, Los Angeles, California, United States Department of Electrical Engineering, University of Southern California, Los Angeles, California, United States.
authors.forename: Norberto M
authors.initials: NM
authors.lastname: Grzywacz
authors.affiliation: Center for Vision Science and Technology, University of Southern California, Los Angeles, California, United States.
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D058449:Intravitreal Injections; D061965:Matrix Metalloproteinase Inhibitors / Q000008:administration & dosage; D018613:Microscopy, Confocal; D051381:Rats; D017207:Rats, Sprague-Dawley; D017949:Retinal Cone Photoreceptor Cells / Q000187:drug effects / Q000473:pathology*; D012174:Retinitis Pigmentosa / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1
keywords: TIMP-1; cones; mosaic; retinitis pigmentosa