Adenylyl and guanylyl cyclase activity in the choroid.

The choroid, a low-resistance vascular structure provides nourishment to and removal of potential toxic waste products from the adjacent non-vascularized outer layers of the retina, macula, and optic disc region and may be involved in the pathology of normal tension glaucoma. This study is aimed at delineating the biochemical pharmacology of vascular tone control in this tissue. By using a procedure to harvest fresh choroidal tissue, we studied some basic characteristics of the adenylyl (AC) and guanylyl cyclase (GC) enzyme systems in this tissue using the 3H-cAMP/32P-ATP tracer method. Compared to respective baseline measurements (100+/-SEM%), AC activity was stimulated (p < 0.05) by forskolin (FSK, 477+/-59%), fluoroaluminate (AlF(4), 360+/-10.3%), isoproterenol (ISO, 129+/-5.5%), vasoactive intestinal peptide (VIP, 132+/-6.1%), calmodulin (CAM)+Mn2+ (196+/-69%), and dose-dependently by prostaglandin (PG) E2 (up to 162+/-3.6%). The antagonist drug calmidazolium inhibited the CAM-dependent increase but also blocked basal activity (47+/-2.0%) without affecting the FSK response. Other CAM blockers (TFP, W5) produced similar results but were not completely selective for CAM-activated cyclase. GDPbetaS, a blocker of G-protein coupling to AC did not affect AC responses to FSK, ISO, and AlF4, but decreased the response to PGE2. N-ethyl-carboxamido adenosine (NECA), which activates adenosine A2 receptors, did not synergize with FSK or add to ISO responses and did not activate AC by itself. In the GC system activity was stimulated (p< 0.05) by CAM+Mn2+ (239+/-27%), by atrial natriuretic peptide (ANP, up to 143+/-1.4%) and sodium nitroprusside (SNP, up to 179+/-1.6%). These results show that choroidal tissue has significant activities of the adenylyl and guanylyl cyclase second messenger systems potentially responsive to hormones/neurotransmitters that may control the degree of relaxation in this vascular tissue.

Short posterior ciliary artery, central retinal artery, and choroidal hemodynamics in brimonidine-treated primary open-angle glaucoma patients.

PURPOSE: Malfunction in peripapillary hemodynamics has been suggested to play a major part in the pathogenesis of primary open-angle glaucoma (POAG). The aim of this study was to determine whether topically applied brimonidine can influence blood hemodynamic characteristics associated with the perioptic short posterior ciliary arteries (SPCAs), central retinal artery (CRA), and choroidal vascular system in POAG patients. DESIGN: Randomized clinical trial. In this prospective, institutional, double-masked, vehicle-controlled, randomized clinical trial, the intraocular pressure (IOP) and vascular dynamics of the SPCAs, CRA, and choroidal vascular system were analyzed in both eyes of 17 POAG patients, before and after treatment with 0.2% brimonidine for 4 weeks. RESULTS: Mean IOP reduction was significant (18.7%) following treatment with brimonidine. However, no clear changes were recorded with respect to blood perfusion parameters (peak systolic velocity, end-diastolic velocity, pulsatility, and resistance indices) associated with the SPCAs and CRA or the choroidal ocular pulse amplitude. CONCLUSIONS: Topical treatment of brimonidine to POAG patients causes a significant reduction of IOP, but blood hemodynamic properties associated with the SPCAs, CRA, and choroidal vascular systems appeared unaffected. Topically applied brimonidine, therefore, appears not to constrict or dilate peripapillary blood vessels.