Outflow Facility in Mice with a Targeted Type I Collagen Mutation

Abstract

Outflow facility is reduced in transgenic Col1a1(r/r) mice with IOP elevation. The inverse correlation of IOP elevation to facility reduction indicates that increased resistance in the aqueous outflow pathway contributes to ocular hypertension in Col1a1(r/r) mice. These mice may be useful as a model for open-angle glaucoma, as well as for assessing the relationship between collagen type I metabolism and aqueous outflow.

Elevated intraocular pressure induces Rho GTPase mediated contractile signaling in the trabecular meshwork

“…This decrease in aqueous outflow facility in eyes perfused at 50 mm Hg was evident from the first hour and persisted till the 4 th hour post baseline perfusion, indicating increased resistance to aqueous outflow in response to elevated perfusion pressure. This observation was found to be consistent with several previous reports in which an inverse association has been confirmed between IOP and AH outflow facility (Battista et al, 2008; Becker and Constant, 1956; Brubaker, 1975; Dai et al, 2009; Hashimoto and Epstein, 1980). These data also indicate that under conditions of acutely increased perfusion pressure, the AH outflow tissues appear to adapt to facilitate increased AH drainage through the conventional pathway within the first hour, based on the observed increase in the aqueous outflow rate in the eyes perfused at 50 mm Hg.…”

Elevated intraocular pressure induces Rho GTPase mediated contractile signaling in the trabecular meshwork

“…This decrease in aqueous outflow facility in eyes perfused at 50 mm Hg was evident from the first hour and persisted till the 4 th hour post baseline perfusion, indicating increased resistance to aqueous outflow in response to elevated perfusion pressure. This observation was found to be consistent with several previous reports in which an inverse association has been confirmed between IOP and AH outflow facility (Battista et al, 2008; Becker and Constant, 1956; Brubaker, 1975; Dai et al, 2009; Hashimoto and Epstein, 1980). These data also indicate that under conditions of acutely increased perfusion pressure, the AH outflow tissues appear to adapt to facilitate increased AH drainage through the conventional pathway within the first hour, based on the observed increase in the aqueous outflow rate in the eyes perfused at 50 mm Hg.…”

Expanding the clinical spectrum of COL1A1 mutations in different forms of glaucoma

“…In addition, they do not present typical clinical signs of OI and EDS like in our first patient. Further, the heterozygous mice carriers have been reported to be without any signs of OI and glaucoma similar phenotype as the parents of our MI-1 patient analyzed [ 14 , 65 , 66 ].…”

Thrombospondin‐1 mediates Rho‐kinase inhibitor‐induced increase in outflow‐facility

“…We show that Y39983 reduces the expression of the tropomyosin beta chain, suggesting that that COL1A1 mutations occur in different forms of glaucoma (Mauri et al, 2016). Transgenic Col1a1 r/r mice have been shown to display an elevated IOP with a reduced outflow facility (Dai et al, 2009).…”

Elevated intraocular pressure induces Rho GTPase mediated contractile signaling in the trabecular meshwork

“…This decrease in aqueous outflow facility in eyes perfused at 50 mm Hg was evident from the first hour and persisted till the 4 th hour post baseline perfusion, indicating increased resistance to aqueous outflow in response to elevated perfusion pressure. This observation was found to be consistent with several previous reports in which an inverse association has been confirmed between IOP and AH outflow facility (Battista et al, 2008; Becker and Constant, 1956; Brubaker, 1975; Dai et al, 2009; Hashimoto and Epstein, 1980). These data also indicate that under conditions of acutely increased perfusion pressure, the AH outflow tissues appear to adapt to facilitate increased AH drainage through the conventional pathway within the first hour, based on the observed increase in the aqueous outflow rate in the eyes perfused at 50 mm Hg.…”

Expanding the clinical spectrum of COL1A1 mutations in different forms of glaucoma

“…In addition, they do not present typical clinical signs of OI and EDS like in our first patient. Further, the heterozygous mice carriers have been reported to be without any signs of OI and glaucoma similar phenotype as the parents of our MI-1 patient analyzed [ 14 , 65 , 66 ].…”

Thrombospondin‐1 mediates Rho‐kinase inhibitor‐induced increase in outflow‐facility

“…We show that Y39983 reduces the expression of the tropomyosin beta chain, suggesting that that COL1A1 mutations occur in different forms of glaucoma (Mauri et al, 2016). Transgenic Col1a1 r/r mice have been shown to display an elevated IOP with a reduced outflow facility (Dai et al, 2009).…”

Elevated intraocular pressure induces Rho GTPase mediated contractile signaling in the trabecular meshwork

“…This decrease in aqueous outflow facility in eyes perfused at 50 mm Hg was evident from the first hour and persisted till the 4 th hour post baseline perfusion, indicating increased resistance to aqueous outflow in response to elevated perfusion pressure. This observation was found to be consistent with several previous reports in which an inverse association has been confirmed between IOP and AH outflow facility (Battista et al, 2008; Becker and Constant, 1956; Brubaker, 1975; Dai et al, 2009; Hashimoto and Epstein, 1980). These data also indicate that under conditions of acutely increased perfusion pressure, the AH outflow tissues appear to adapt to facilitate increased AH drainage through the conventional pathway within the first hour, based on the observed increase in the aqueous outflow rate in the eyes perfused at 50 mm Hg.…”

Expanding the clinical spectrum of COL1A1 mutations in different forms of glaucoma

“…In addition, they do not present typical clinical signs of OI and EDS like in our first patient. Further, the heterozygous mice carriers have been reported to be without any signs of OI and glaucoma similar phenotype as the parents of our MI-1 patient analyzed [ 14 , 65 , 66 ].…”

Thrombospondin‐1 mediates Rho‐kinase inhibitor‐induced increase in outflow‐facility

“…We show that Y39983 reduces the expression of the tropomyosin beta chain, suggesting that that COL1A1 mutations occur in different forms of glaucoma (Mauri et al, 2016). Transgenic Col1a1 r/r mice have been shown to display an elevated IOP with a reduced outflow facility (Dai et al, 2009).…”