Thrombospondin-1 (TSP1)-Null and TSP2-null mice exhibit lower intraocular pressures

Ramez I. Haddadin, Dong Jin Oh, Min Hyung Kang, Guadalupe Villarreal Jr, Ja Heon Kang, Rui Jin, Haiyan Gong, Douglas J. Rhee

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Purpose. 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.

Original languageEnglish (US)
Pages (from-to)6708-6717
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume53
Issue number10
DOIs
StatePublished - Sep 1 2012

Fingerprint

Thrombospondin 1
Intraocular Pressure
Transmission Electron Microscopy
Extracellular Matrix
Trabecular Meshwork
Light
Optical Coherence Tomography
Cytoskeleton
Cadaver
Fluorescence Microscopy
Cell Adhesion
Fluorescent Antibody Technique
Microscopy
Collagen

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Haddadin, Ramez I. ; Oh, Dong Jin ; Kang, Min Hyung ; Jr, Guadalupe Villarreal ; Kang, Ja Heon ; Jin, Rui ; Gong, Haiyan ; Rhee, Douglas J. / Thrombospondin-1 (TSP1)-Null and TSP2-null mice exhibit lower intraocular pressures. In: Investigative Ophthalmology and Visual Science. 2012 ; Vol. 53, No. 10. pp. 6708-6717.
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abstract = "Purpose. 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.",
author = "Haddadin, {Ramez I.} and Oh, {Dong Jin} and Kang, {Min Hyung} and Jr, {Guadalupe Villarreal} and Kang, {Ja Heon} and Rui Jin and Haiyan Gong and Rhee, {Douglas J.}",
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Thrombospondin-1 (TSP1)-Null and TSP2-null mice exhibit lower intraocular pressures. / Haddadin, Ramez I.; Oh, Dong Jin; Kang, Min Hyung; Jr, Guadalupe Villarreal; Kang, Ja Heon; Jin, Rui; Gong, Haiyan; Rhee, Douglas J.

In: Investigative Ophthalmology and Visual Science, Vol. 53, No. 10, 01.09.2012, p. 6708-6717.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Thrombospondin-1 (TSP1)-Null and TSP2-null mice exhibit lower intraocular pressures

AU - Haddadin, Ramez I.

AU - Oh, Dong Jin

AU - Kang, Min Hyung

AU - Jr, Guadalupe Villarreal

AU - Kang, Ja Heon

AU - Jin, Rui

AU - Gong, Haiyan

AU - Rhee, Douglas J.

PY - 2012/9/1

Y1 - 2012/9/1

N2 - Purpose. 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.

AB - Purpose. 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.

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