Regulation of Glucocorticoid Responsiveness in Glaucomatous Trabecular Meshwork Cells by Glucocorticoid Receptor-β

Abstract

The decreased amount of GRbeta in glaucomatous TM cells could result in enhanced glucocorticoid responsiveness and ocular hypertension.

Dexamethasone inhibition of trabecular meshwork cell phagocytosis and its modulation by glucocorticoid receptor β

“…A and D). This is consistent with the previous report that normal TM cells had a higher GRβ expression compared to glaucomatous TM cells did (Zhang et al, 2005). In general, primary cultured TM cells appeared to phagocytose more bioparticles than transformed TM cells.…”

“…Previously, we reported that GTM-3 cells expressed relatively lower levels of GRβ and were more responsive to DEX in the induction of fibronectin, myocilin, and a GRE-luciferase reporter gene (Zhang et al, 2005). We showed that GRβ was a key regulator of this increased responsiveness, and suggested that GRβ may modulate DEX mediated suppression of TM cell phagocytosis.…”

Dexamethasone inhibition of trabecular meshwork cell phagocytosis and its modulation by glucocorticoid receptor β

“…A and D). This is consistent with the previous report that normal TM cells had a higher GRβ expression compared to glaucomatous TM cells did (Zhang et al, 2005). In general, primary cultured TM cells appeared to phagocytose more bioparticles than transformed TM cells.…”

“…Previously, we reported that GTM-3 cells expressed relatively lower levels of GRβ and were more responsive to DEX in the induction of fibronectin, myocilin, and a GRE-luciferase reporter gene (Zhang et al, 2005). We showed that GRβ was a key regulator of this increased responsiveness, and suggested that GRβ may modulate DEX mediated suppression of TM cell phagocytosis.…”

RANKL Inhibition and the Risk of Ocular Hypertension and Primary Open-Angle Glaucoma

“…Glucocorticoids can raise intraocular pressure, and individuals predisposed to POAG tend to exhibit greater sensitivity to steroid-induced pressure elevation. 44 We observed a lower glaucoma risk among corticosteroid users, indicating that denosumab may demonstrate a comparable risk-lowering pattern in this high-risk population. Notably, denosumab is known to more effectively inhibit RANKL-mediated pathways activated during glucocorticoid exposure, 45 , 46 providing a potential biological context for this observation.…”

FK506-Binding Protein 51 Regulates Nuclear Transport of the Glucocorticoid Receptor β and Glucocorticoid Responsiveness

“…40,41 Previously, we reported that glaucomatous TM cell lines (including GTM-3) had lower levels of GR␤ than did normal TM cell lines (including NTM-5). 19 It is possible that FKBP51 structural differences in GTM-3 could affect its interaction with GR␤ and Hsp90 complex, disrupt the constitutive nuclear transport of GR␤, and consequently decrease the amount of nuclear GR␤ that we saw previously. It is also possible that FK506 interacts with FKBP51 in GTM-3 differently and fails to modulate FKBP51 chaperone function, as seen in this study.…”

Dexamethasone inhibition of trabecular meshwork cell phagocytosis and its modulation by glucocorticoid receptor β

“…A and D). This is consistent with the previous report that normal TM cells had a higher GRβ expression compared to glaucomatous TM cells did (Zhang et al, 2005). In general, primary cultured TM cells appeared to phagocytose more bioparticles than transformed TM cells.…”

“…Previously, we reported that GTM-3 cells expressed relatively lower levels of GRβ and were more responsive to DEX in the induction of fibronectin, myocilin, and a GRE-luciferase reporter gene (Zhang et al, 2005). We showed that GRβ was a key regulator of this increased responsiveness, and suggested that GRβ may modulate DEX mediated suppression of TM cell phagocytosis.…”

RANKL Inhibition and the Risk of Ocular Hypertension and Primary Open-Angle Glaucoma

“…Glucocorticoids can raise intraocular pressure, and individuals predisposed to POAG tend to exhibit greater sensitivity to steroid-induced pressure elevation. 44 We observed a lower glaucoma risk among corticosteroid users, indicating that denosumab may demonstrate a comparable risk-lowering pattern in this high-risk population. Notably, denosumab is known to more effectively inhibit RANKL-mediated pathways activated during glucocorticoid exposure, 45 , 46 providing a potential biological context for this observation.…”

FK506-Binding Protein 51 Regulates Nuclear Transport of the Glucocorticoid Receptor β and Glucocorticoid Responsiveness

“…40,41 Previously, we reported that glaucomatous TM cell lines (including GTM-3) had lower levels of GR␤ than did normal TM cell lines (including NTM-5). 19 It is possible that FKBP51 structural differences in GTM-3 could affect its interaction with GR␤ and Hsp90 complex, disrupt the constitutive nuclear transport of GR␤, and consequently decrease the amount of nuclear GR␤ that we saw previously. It is also possible that FK506 interacts with FKBP51 in GTM-3 differently and fails to modulate FKBP51 chaperone function, as seen in this study.…”

Dexamethasone inhibition of trabecular meshwork cell phagocytosis and its modulation by glucocorticoid receptor β

“…A and D). This is consistent with the previous report that normal TM cells had a higher GRβ expression compared to glaucomatous TM cells did (Zhang et al, 2005). In general, primary cultured TM cells appeared to phagocytose more bioparticles than transformed TM cells.…”

“…Previously, we reported that GTM-3 cells expressed relatively lower levels of GRβ and were more responsive to DEX in the induction of fibronectin, myocilin, and a GRE-luciferase reporter gene (Zhang et al, 2005). We showed that GRβ was a key regulator of this increased responsiveness, and suggested that GRβ may modulate DEX mediated suppression of TM cell phagocytosis.…”

RANKL Inhibition and the Risk of Ocular Hypertension and Primary Open-Angle Glaucoma

“…Glucocorticoids can raise intraocular pressure, and individuals predisposed to POAG tend to exhibit greater sensitivity to steroid-induced pressure elevation. 44 We observed a lower glaucoma risk among corticosteroid users, indicating that denosumab may demonstrate a comparable risk-lowering pattern in this high-risk population. Notably, denosumab is known to more effectively inhibit RANKL-mediated pathways activated during glucocorticoid exposure, 45 , 46 providing a potential biological context for this observation.…”

FK506-Binding Protein 51 Regulates Nuclear Transport of the Glucocorticoid Receptor β and Glucocorticoid Responsiveness

“…40,41 Previously, we reported that glaucomatous TM cell lines (including GTM-3) had lower levels of GR␤ than did normal TM cell lines (including NTM-5). 19 It is possible that FKBP51 structural differences in GTM-3 could affect its interaction with GR␤ and Hsp90 complex, disrupt the constitutive nuclear transport of GR␤, and consequently decrease the amount of nuclear GR␤ that we saw previously. It is also possible that FK506 interacts with FKBP51 in GTM-3 differently and fails to modulate FKBP51 chaperone function, as seen in this study.…”