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Abstract #28165 Published in IGR 13-1
Use of calcium channel blockers for glaucoma
Araie M; Mayama CProgress in Retinal and Eye Research 2011; 30: 54-71
Calcium channel blockers (CCBs), which alter the intracellular calcium concentration by modifying calcium flux across cell membranes and affect various intracellular signaling processes, have been long and widely used to treat essential hypertension and certain types of cardiac diseases such as angina pectoris. Among five subtypes of calcium channels, only specific agents for L-type calcium channels have been used as therapeutics. Animal experiments have indicated that topical application of CCBs, especially verapamil, caused significant intraocular pressure (IOP) reductions, while ocular hypotensive effects in humans were not substantial. Although the results obtained for nifedipine and nimodipine were not always consistent, CCBs generally dilate isolated ocular vessels and increase ocular blood flow in experimental animals, normal humans, and patients with open-angle glaucoma (OAG). Several single-centered, hospital-based, prospective studies have suggested that nimodipine, brovincamine, and nilvadipine had beneficial effects on visual function not only in normal humans but also in patients with OAG, while the results of population-based and case-controlled studies were not always consistent with those obtained in hospital-based studies. In vitro studies showed that CCBs exerted neuroprotective effects on neurons undergoing apoptosis and necrosis. Although the neuroprotective effects of CCBs have been well documented in experimental cerebral ischemia models, no controlled studies have shown the clinical efficacy of CCBs in stroke or cerebral ischemia. Neuroprotective effects also were documented in retinal ganglion cells and photoreceptors in experimental animals. Some ophthalmic beta-adrenoceptor antagonists, especially betaxolol, interact with L-type calcium channels and show calcium channel-blocking activity, which may be partly responsible for the neuroprotective effects of these drugs reported in experimental animals. Based on the reported findings of CCBs and that the results of clinical studies in acute cerebral ischemia may not be directly applicable to a chronic neurodegenerative ocular disorder, such as OAG, CCBs deserve future study to investigate strategies that are additive or synergetic to ocular hypotensive therapy for OAG, especially in patients with lower IOP.
M. Araie. Department of Ophthalmology, University of Tokyo Graduate School of Medicine, 7-3-1, Hongo, Bunkyo-ku, 113-8655 Tokyo, Japan. araie-tky@umin.net
Classification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
