Beta-adrenoceptors and intraocular pressure

Primary open angle glaucoma (P. O. A. G. ) is a major cause of blindness throughout the world. This disease is characterised by raised intraocular pressure (I. O. P. ) leading to progressive vision loss. Topical beta blockers decrease aqueous production and therefore lower I. O. P. How beta blockers decrease aqueous production is not known. It is presumed they exert their I. O. P. lowering effect by binding to ciliary process beta-adrenoceptors. The purpose of this study was to determine whether beta-adrenoceptors exist in pigmented ciliary process; to determine the subtype (Beta-1 or Beta-2) of receptor present in the ciliary processes; to determine which beta blocker binds most potently to the receptors in vitro and finally to determine whether specific beta blockers inhibit aqueous production and lower I. O. P. The results of the radioligand binding portion of this study indicate that beta-adrenoceptors do exist in pigmented animal ciliary processes (Bmax = 98.0 (+ 7.30) fmol/mg protein, KD = . 363 (+ 0.01) nM) and they are of the Beta-2 subtype. The Beta-2 blockers LI 32-468, ICI 118551 and IPS 339 bind potently to these receptors (mean values 2.91 x 10-8 M, 4.65 x 10-8 M, 8.16 x 10-8 M respectively). The results of I. O. P. recovery rate experiments (aqueous humour index) indicate that Beta-2 specific blockers significantly inhibit rabbit aqueous humour production. The results of studies on rabbits with glaucoma revealed that Beta-2 blockers lower intra-ocular pressure. In conclusion, this is the first study implicating Beta-2 adrenoceptors as the major receptor subtype controlling aqueous production and I. O. P. Furthermore, the results of this study indicate that Beta-2 blockers may prove to be a valuable new treatment for patients with glaucoma