vasoactive-intestinal-peptide and Ocular-Hypertension

To investigate the roles of vasoactive intestinal peptides (VIPs) in regulating the morphology and F-actin distribution of Schlemm's canal (SC) of rat eyes.. Chronic intraocular pressure (IOP) hypertension models with episcleral venous cauterization (EVC) were treated with topical VIP or PG99-465 (vasoactive intestinal peptide receptors 2 [VPAC2] antagonist). IOPs were measured with Tono-Pen, and the SC parameters, including the cross-section area, circumference, and length, were statistically evaluated by hematoxylin-eosin and CD31 immunohistochemical staining. Immunofluorescence was performed to detect the distribution of F-actin in the SC. Moreover, the distribution of filamentous actin (F-actin) and globular actin (G-actin) in human umbilical vein endothelial cells (HUVECs) was studied under a pressure system by immunofluorescence and Western blotting.. Increased expressions of VIP and VPAC2 receptors, as well as a disordered distribution of F-actin were found in SC endothelial cells (SCEs) in the EVC model. Moreover, topical VIP maintained the normal distribution of F-actin in SCEs, expanded the collapsed SC, and induced a significant decrease in IOP in the EVC model. In in vitro HUVECs, the F-actin/G-actin ratio increased significantly under stress stimulation for 30 minutes. A total of 50 μM VIP helped maintain the normal F-actin/G-actin ratio of HUVECs against stress stimulation.. VIP regulates the distribution of F-actin in SCEs via the VPAC2 receptor in order to induce a decrease in IOP. VIP may represent a new target for antiglaucoma drugs.

Topics: Actins; Animals; Blotting, Western; Chronic Disease; Disease Models, Animal; Fluorescent Antibody Technique, Indirect; Human Umbilical Vein Endothelial Cells; Humans; Intraocular Pressure; Limbus Corneae; Male; Ocular Hypertension; Rats; Rats, Sprague-Dawley; Receptors, Vasoactive Intestinal Peptide, Type II; Tonometry, Ocular; Trabecular Meshwork; Vasoactive Intestinal Peptide

The effects of repeated topical administration of the selective beta 2-adrenergic agonist fenoterol on the intraocular pressure and on the adenylyl cyclase activity in ciliary processes in rabbit were examined in order to detect their possible causal relationship.. Intraocular pressure was measured by pneumatonometry. Adenylyl cyclase activity in homogenates of ciliary processes was assayed ex vivo by measurement of conversion of 32P-alpha-ATP to 32P-cyclic AMP.. A single topical dose of 1% solution of fenoterol elicited a clear-cut decrease of the intraocular pressure lasting for several h. Repeated administration of fenoterol for 2-5 days led to a significant increase of intraocular pressure, observable from the second to the fifth day. The stimulation of adenylyl cyclase activity ex vivo by isoproterenol, vasoactive intestinal polypeptide or forskolin was significantly decreased on the fifth day (24 h after the administration of the last dose of fenoterol).. Our data showed that repeated topical administration of the selective beta 2-adrenergic agonist increased intraocular pressure and desensitized adenylyl cyclase in ciliary processes; if these two effects are related then they would support the idea of direct relationship of decreased cAMP production in ciliary processes to the increase of intraocular pressure, and vice versa. However, conclusive evidence of this suggestion and of its possible significance in another animal species or man would require further study.

Topics: Adenylyl Cyclases; Administration, Topical; Adrenergic beta-Agonists; Animals; Ciliary Body; Colforsin; Fenoterol; Intraocular Pressure; Isoproterenol; Ocular Hypertension; Ophthalmic Solutions; Rabbits; Tonometry, Ocular; Vasoactive Intestinal Peptide