Veluchamy Amutha Barathi, Adriana Katz, Shashikant Chaudhary, Hoi-Lam Li, Daniel M Tal, Arie L Marcovich, Chi-Wai Do, Steven J D Karlish
Glaucoma is a blinding disease. Reduction of intraocular pressure (IOP) is the mainstay of treatment, but current drugs show side-effects or become progressively ineffective, highlighting the need for novel compounds. We have synthesized a family of perhydro-1,4-oxazepine derivatives of digoxin, the selective inhibitor of Na,K-ATPase. The cyclobutyl derivative (DcB) displays strong selectivity for the human a2 isoform and potently reduces IOP in rabbits. These observations appeared consistent with a hypothesis that in ciliary epithelium DcB inhibits the a2 isoform of Na,K-ATPase, which is expressed strongly in non-pigmented cells, reducing aqueous humor (AH) inflow...
April 1, 2024: American Journal of Physiology. Cell Physiology