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In an ex vivo rat glaucoma model using dissected retinas, the neurosteroid allopregnanolone (AlloP) protects retinal ganglion cells (RGCs) via GABR/GABAA receptors. To determine the involvement of macroautophagy/autophagy in neuroprotection by AlloP, we examined the effects of autophagy activators, rapamycin and torin 2, and autophagy inhibitors, bafilomycin A1 and SAR405, on retinal retinal morphology and expression of MAP1 LC3B/LC3B (microtubule-associated protein 1 light chain 3 beta) and SQSTM1 (sequestosome 1). Administration of rapamycin or torin 2 exerted partial histological neuroprotection, while combined administration of AlloP with bafilomycin A1 or SAR405 induced severe degeneration in a hyperbaric condition. Electron microscopic analyses showed that the addition of AlloP significantly increased autophagosomes and degenerative autophagic vacuoles in the retinal nerve fiber layer. Immunoblotting showed that the addition of AlloP or autophagic activators increased the lipidated form of LC3B (LC3B-II) and suppressed SQSTM1. Moreover, bafilomycin A1 increased LC3B-II and SQSTM1 protein levels in the presence of AlloP without changes in corresponding mRNAs compared to AlloP-treated retinas in a hyperbaric condition. These data indicate that AlloP likely induces a protective form of autophagy in this model. In an in vivo rat model of glaucoma, we also observed neuroprotective effects of AlloP. Injection of polystyrene microbeads into the anterior chamber increased intraocular pressure about 3-fold and induced RGC apoptosis. A single intravitreal injection of AlloP or autophagy activators prevented apoptosis and protected RGCs with autophagy activation. We conclude that AlloP may serve as a potential therapeutic agent for the treatment of glaucoma via diverse mechanisms. Abbreviations: 2HBCD: 2-Hydroxypropyl)-β-cyclodextrin; 3-MA: 3-methyladenine; AlloP: allopregnanolone; AP: autophagosome; AVd: degradative autophagic vacuoles; GCL: ganglion cell layer; INL: inner nuclear layer; IOP: intraocular pressure; IPL: inner plexiform layer; LC3B-I: cytosolic form of LC3B; LCB-II: lipidated form of LC3B; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; mPTP: mitochondrial permeability transition pore; NDS: neuronal damage score; NFL: nerve fiber layer; OH: ocular hypertension; ON: optic nerve; ONL: outer nuclear layer; OPL: outer plexiform layer; p-STR: scotopic threshold response; RGC: retinal ganglion cells; RT-PCR: real-time reverse transcription polymerase chain reaction; SQSTM1: sequestosome 1; TUNEL: TdT-mediated dUTP Nick End Labeling [ABSTRACT FROM AUTHOR]

Purpose: To estimate the prevalence and risk factors for polypoidal choroidal vasculopathy (PCV) in a general Japanese population.Methods: This population-based, cross-sectional study was conducted in 2007 with subjects from the Hisayama Study. Of the 3,648 residents in Hisayama, Japan, 2,663 who were ≥ 50 years old were enrolled in this study. The characteristics of PCV were determined by fundus examination or based on indocyanine green and fluorescein angiographic findings. We evaluated the contributions of the risk factors for PCV.Results: Among the 207 participants with age-related macular degeneration (AMD), 174 (6.5%) had early AMD, and 33 (1.2%) had late AMD, including 10 participants with PCV (0.4%). Male and smoking habit were significant risk factors for the development of PCV.Conclusions: The prevalence of PCV is higher among Japanese subjects than Caucasians in Western countries. Male gender and smoking habit were significant risk factors for PCV in a general Japanese population. [ABSTRACT FROM AUTHOR]

Purpose : To investigate the effects of prostaglandin (PG) E 1 , E 2 , F 2α , and latanoprost acid on the electrically evoked contractile response of isolated rhesus monkey ciliary muscle. Methods : Longitudinal ciliary muscle preparations from rhesus monkeys were mounted in an organ bath, and tension changes were recorded by an isometric transducer. Electrical field stimulation (100 Hz, 0.3 ms, 10 V) was applied through a pair of platinum plate electrodes. Results : The ciliary muscle produced atropine-sensitive excitatory contraction in response to field stimulation. PGE 1 and PGE 2 (1 μ M) attenuated the contraction to levels that were 68% and 65.1%, respectively, of the normal amplitude. However, PGF 2α and latanoprost acid (1 μ M) did not significantly change the response amplitude. Conclusions : Our results indicate that PGF 2α and latanoprost acid do not interact with the prostanoid receptor involved at the pre- and/or postsynaptic site. Therefore, it is unlikely that the hypotensive action by these agents is due to relaxation of the ciliary muscle. [ABSTRACT FROM AUTHOR]

Purpose. To clarify the vasodilator mechanism of unoprostone isopropyl (unoprostone), a PG F2α related compound used for treatment of glaucoma, we have investigated the effect of this drug and its metabolites on isolated rabbit ciliary artery in vitro. Methods. Under the dissecting microscope, ciliary arteries were prepared from albino rabbit eyes and mounted in a mayo-graph system. The effects of unoprostone isopropyl and other agents were investigated using isometric tension recording methods. Results. Unoprostone induced a dose-dependent relaxation in ciliary arteries that were pre-contracted with high-K solution, 10μM histamine or 10μM PG F2α. Neither unoprostone metabolite M1 or M2 had a relaxant effect on the reconstructed vessels. Relaxation was unaffected by inhibition of ardently cycles with SQ 22536, guanylyl cyclase with ODQ, or maxi-K channels with iberiotoxin. Pretreatment with unoprostone did not affect histamine-induced transient contractions in Ca2+ -free solution. However. SKF9365. a general Ca2+ channel blocker. evoked relaxation similar to unoprostone with respect to amplitude and rate of onset. Conclusions. Unoprostone, but not its metabolites M1 and M2, relaxed pre-contracted rabbit ciliary artery. The mechanism of vascular smooth muscle relaxation by unoprostone differs from that of IOP reduction and does not depend on adenylyl cyclase, guanylyl cyclase, or maxi-K channels. Relaxation may be mediated by inhibition of Ca2+ entry, possibly through capacitative Ca2+ channels. [ABSTRACT FROM AUTHOR]

Discusses pupil perimetry and Humphrey field analysis in Leber hereditary optic neuropathy compared with optic neuritis. Quantitative analysis conducted in the superotemporal, superonasal, inferotemporal and inferonasal quadrants; Comparisons which show that pupil perimetry provided better results than Humphrey perimetry.

Purpose. To characterize in vivo changes of adenylate cyclase activity in rabbit ciliary processes during the circadian cycle. Methods. After removal of vitreous, lens, retina and choroid from freshly enucleated rabbit eyes, the anterior segment and attached sclera was chilled in cold buffer containing the nonselective phosphodiesterase (PDE) inhibitor, 3-isobutyl-1-methylxanthine (IBMX). Then ciliary processes were excised and homogenized in ice cold trichloro-acetic acid (TCA) 2.5 min after IBMX treatment. Increased cyclic AMP in response to PDE inhibition was measured in ciliary processes at six times during the circadian cycle, after preganglionic section of the cervical sympathetic trunk (decentralization, DX), and after topical instillation of hydroxyamphetamine, timolol, brimonidine, rauwolscine or a soluble derivative of forskolin. Results. The increase of rabbit ciliary process cyclic AMP levels in response to PDE inhibition with IBMX was enhanced at night. Much of the enhanced nocturnal increase persisted in constant dark and was blunted by DX. Topical instillation of hydroxyamphetamine enhanced the increase during the day; whereas, timolol, a β-adrenergic antagonist, or brimonidine, an α[sub 2]-adrenergic agonist, blunted the IBMX induced increase. Neither instillation of rauwolscine, an α[sub 2]adrenergic antagonist, nor the soluble forskolin derivative enhanced the increase of cyclic AMP after IBMX. Conclusions. The technique reported here can be used to estimate ciliary process adenylate cyclase activity in vivo. There is a circadian rhythm of adenylate cyclase activity in rabbit ciliary processes that is driven in part by ocular sympathetic input and stimulation of β-adrenergic receptors. [ABSTRACT FROM AUTHOR]

PURPOSE. A disturbance in ocular blood flow is an important factor in the pathogenesis of visual damage caused by glaucoma. We investigated the innervation of the ciliary artery, important to blood flow in the optic nerve head, and the effects of pilocarpine thereon. METHODS. Ciliary arteries were prepared from rabbit eyes and mounted in a myograph system. The effects of electrical nerve stimulation and pilocarpine on the isolated rabbit ciliary artery were investigated using isometric tension recording methods. RESULTS. Electrical field stimulation evoked contraction of the ciliary artery, which was inhibited by pretreatment with 10 μM bunazosin. Electrical field stimulation also evoked relaxation when the ciliary artery was pre-contracted by 10 μM histamine in the presence or absence of endothelium. This relaxation was inhibited by pretreatment with 10 μM NG-nitro-L-arginine methylester (L-NAME). Pilocarpine administration produced a dose-dependent muscle relaxation that was abolished by treatment with L-NAME, 1 æM atropine, or denudation of the endothelium. CONCLUSIONS. Results indicate that the rabbit ciliary artery is innervated by at least two different types of nerves, adrenergic nerves, which evoke contraction and nerve fibers that cause an endothelium-independent release of nitric oxide (NO). Pilocarpine relaxation of this muscle was dependent on the endothelium and NO synthesis. [ABSTRACT FROM AUTHOR]