Beta-Blocking Agents Inhibit Na⁺K⁺ATPase in Cultured Corneal Endothelial and Epithelial Cells

The Inhibition of Na, K-ATPase, and Mg-ATPase by Timolol Maleate in Cultured Non-Pigmented Epithelial Cells of the Ciliary Body

“…with Kj values in the range of 1010 to 10"9 M. Although the K} estimate in this study may be in error due to other binding phenomena which partially reverses the inhibition curve (above 106 M), we estimate the same Kj value for the inhibition ofNa, K-ATPase and a Kj = 1012 M by betaxolol for the same enzyme in cornealendothelial cultured cells (7). Furthermore, a K, = 10" M by timolol for Na,K-ATPase in corneal epithelial cultured cells can be estimated from the same study.…”

“…However, reviews (1,2,3) and recent publications (4,5,6) indicate that the actual mechanism of these agents for reducing IOP has not yet been described. In 1991, Whikehart et al (7) reported the inhibition of plasma membrane Na,K-ATPase (E.C. 3.6.1.37) in cultured, corneal endothelial and epithelial cells with timolol maléate and betaxolol hydrochloride.…”

The Multifarious Effects of Various Glaucoma Pharmacotherapy on Corneal Endothelium: A Narrative Review

“…A trend of timolol to increase corneal thickness in human CECs in vivo has additionally been described [ 28 ], a fact that could possibly be attributed to the aforementioned increase in intracellular calcium concentration that timolol induces [ 21 ]. According to Whikehart et al., timolol maleate and betaxolol have also been found to significantly inhibit Na + /K + -ATPase in corneal endothelium [ 30 ], an effect that could account for corneal thickness changes as well.…”

“…(1983) [ 26 ] In vivo Timolol caused small areas of endothelial cell degeneration and breakdown in treated rabbit eyes Timolol Whikehart et al. (1991) [ 30 ] In vitro In cultured corneal endothelial and epithelial cells, a decrease in activity is indicated at just under 10–15 M (fM) for Na/K-ATPase; however, the loss of activity does not become significant until 0.42 pM ( p < 0.001) Timolol Lass et al. (1998) [ 36 ] In vivo The mean percent change in CCT at 12 months from baseline was a decrease of 0.25% for timolol group.…”

“…Timolol 0.5% (BID) caused a statistically significant percent HEX increase from baseline to month 3 in HCECs in vivo Betaxolol Whikehart et al. (1991) [ 30 ] In vitro In cultured corneal endothelial and epithelial cells, a decrease in activity of Na/K-ATPase becomes significant after 5 nM level is reached Betaxolol Lass et al. (1998) [ 36 ] In vivo The mean percent change in CCT at 12 months from baseline was an increase of 0.39% for betaxolol group The mean percent endothelial cell loss (4.5%) and percent change in corneal thickness was similar in timolol, betaxolol, and dorzolamide groups at both 6 and 12 months from baseline Betaxolol Wu et al.…”