PURPOSE: Cultured human trabecular meshwork (TM) cells possess substantial Na-K-Cl activity, which is involved in the regulation of TM cell volume. The hypothesis in the present study was that drugs that affect the cotransporter might alter aqueous humor outflow facility (C) in the intact eye. The effects of agents and conditions known to modulate Na-K-CI cotransport activity and/or TM cell volume on C in perfused anterior segments were investigated. METHODS: Human and calf eyes were dissected and perfused, and C was determined according to standard published methods. Perfusates with modified osmolarity were used to cause alterations in TM cell volume. Cl-free perfusate and/or bumetanide (10(-5) M) was used to inhibit Na-K-Cl cotransport activity, and vasopressin (10(-7) M, 10(-8) M) was used to stimulate cotransport activity. RESULTS: In human eyes, hypo-osmotic perfusate decreased C 12%, whereas hyper-osmotic perfusate increased C 44%. These changes lasted approximately 30 minutes, after which C began to normalize. Inhibition of Na-K-Cl cotransport using Cl-free medium or bumetanide resulted in facility increases of 27% and 22%, respectively. There was an additive increase in C with bumetanide plus Cl-free media. Stimulating Na-K-Cl cotransport with 10(-8)M and 10(-7)M vasopressin resulted in 28% and 35% decreases in C, respectively. The results were similar in calf eyes: Cl-free medium or bumetanide resulted in 41% and 52% increases in C, whereas 10(-8) M and 10(-7) M vasopressin resulted in 14% and 19% decreases in C, respectively. CONCLUSIONS: Modulation of Na-K-Cl cotransport results in changes in C that may be mediated in part by cell volume changes.
PURPOSE: Cultured human trabecular meshwork (TM) cells possess substantial Na-K-Cl activity, which is involved in the regulation of TM cell volume. The hypothesis in the present study was that drugs that affect the cotransporter might alter aqueous humor outflow facility (C) in the intact eye. The effects of agents and conditions known to modulate Na-K-CI cotransport activity and/or TM cell volume on C in perfused anterior segments were investigated. METHODS:Human and calf eyes were dissected and perfused, and C was determined according to standard published methods. Perfusates with modified osmolarity were used to cause alterations in TM cell volume. Cl-free perfusate and/or bumetanide (10(-5) M) was used to inhibit Na-K-Cl cotransport activity, and vasopressin (10(-7) M, 10(-8) M) was used to stimulate cotransport activity. RESULTS: In human eyes, hypo-osmotic perfusate decreased C 12%, whereas hyper-osmotic perfusate increased C 44%. These changes lasted approximately 30 minutes, after which C began to normalize. Inhibition of Na-K-Cl cotransport using Cl-free medium or bumetanide resulted in facility increases of 27% and 22%, respectively. There was an additive increase in C with bumetanide plus Cl-free media. Stimulating Na-K-Cl cotransport with 10(-8)M and 10(-7)M vasopressin resulted in 28% and 35% decreases in C, respectively. The results were similar in calf eyes: Cl-free medium or bumetanide resulted in 41% and 52% increases in C, whereas 10(-8) M and 10(-7) M vasopressin resulted in 14% and 19% decreases in C, respectively. CONCLUSIONS: Modulation of Na-K-Cl cotransport results in changes in C that may be mediated in part by cell volume changes.
Authors: J C Fleischhauer; C H Mitchell; W D Stamer; M O Karl; K Peterson-Yantorno; M M Civan Journal: J Membr Biol Date: 2003-05-15 Impact factor: 1.843
Authors: Charles W McLaughlin; Mike O Karl; Sylvia Zellhuber-McMillan; Zhao Wang; Chi Wai Do; Chi Ting Leung; Ang Li; Richard A Stone; Anthony D C Macknight; Mortimer M Civan Journal: Am J Physiol Cell Physiol Date: 2008-08-27 Impact factor: 4.249
Authors: Ang Li; Chi Ting Leung; Kim Peterson-Yantorno; W Daniel Stamer; Claire H Mitchell; Mortimer M Civan Journal: J Cell Physiol Date: 2012-01 Impact factor: 6.384
Authors: Hoi-Lam Li; Sze Wan Shan; W Daniel Stamer; King-Kit Li; Henry Ho-Lung Chan; Mortimer M Civan; Chi-Ho To; Thomas Chuen Lam; Chi-Wai Do Journal: Int J Mol Sci Date: 2022-07-01 Impact factor: 6.208
Authors: Juni Banerjee; Chi-Ting Leung; Ang Li; Kim Peterson-Yantorno; Huan Ouyang; W Daniel Stamer; Mortimer M Civan Journal: Invest Ophthalmol Vis Sci Date: 2017-01-01 Impact factor: 4.799
Authors: Bettina Hohberger; Rudolf Kunze; Gerd Wallukat; Katja Kara; Christian Y Mardin; Robert Lämmer; Ursula Schlötzer-Schrehardt; Sami Hosari; Folkert Horn; Luis Munoz; Martin Herrmann Journal: Front Immunol Date: 2019-10-01 Impact factor: 7.561