New insights into the subjective perception of visual field defects.

Most glaucoma patients are unaware of their visual problem until a late stage of the disease, probably because their visual field defects are being filled-in by the brain. According to new insights into how our brain works, plasticity of the visual cortex allows the brain to reorganize after damage to the retina or the visual pathways. This plasticity involves activation of existing but normally ineffective synapses, in a highly organized system of long-range horizontal connections in the visual cortex. Normal cells in the cortex surrounding the lesion thus take control of the deprived ones. As a result, glaucomatous field defects are probably concealed in the colors and patterns of the surround, up to the point where visual input has decreased to such an extent that the brain is not able anymore to compose a plausible image.

In vitro studies of the effects of beta-adrenergic drugs on retinal and posterior ciliary microarteries.

The small-vessel myograph allows for precise measurements of physiopharmacologic responses of the ocular microarteries under controlled conditions. Studies using the myograph have shown that beta-adrenergic agonists are unable to induce significant relaxation in retinal and posterior ciliary microarteries, indicating that these microarteries have very few or no functional beta-adrenoceptors. Thus, beta-blockers would not be expected to have important adverse vasoconstrictory effects in the posterior part of the eye that are caused by their beta-adrenoceptor binding capacities. On the contrary, some beta-blockers, such as propranolol (the standard beta-blocker in pharmacology) and betaxolol (a beta-blocker used in ophthalmology), have vasorelaxant effects, probably a result of their Ca2+ channel-blocking activity. This activity shows no stereospecificity. Betaxolol could thus act as a vasodilator in glaucoma patients, on the condition that it penetrates in the posterior part of the eye after topical application. If so, it could also induce vasodilatation in circumstances of vascular endothelium injury, because this effect is endothelium-independent.

Ca2+ channel-blocking activity of propranolol and betaxolol in isolated bovine retinal microartery.

The relaxant action of the standard beta-blocker propranolol was compared with betaxolol, a beta-blocker with established vasorelaxant properties. Ring segments of bovine retinal microartery (n=36, theta=237 microm), which lacks adrenergic nerves and beta-adrenoceptors, were mounted in an organ bath for isometric force recording. l-, d-, dl-Propranolol and betaxolol were equally effective in relaxing tonic K+-induced contractions. The median effective dose (ED50) value was approximately 10(-5) M for both beta-blockers. The relaxation by both beta-blockers was unaffected by endothelium removal. Like verapamil, both beta-blockers induced smaller relaxation of tonic prostaglandin F2alpha (PGF2alpha)-induced force, which depended less on Ca2+ influx than did K+-induced force: K+-, but not PGF2alpha-induced contractions were abolished in Ca2+-free medium. The minor betaxolol-induced relaxation of tonic PGF2alpha-induced force was blocked in Ca2+-free medium. With repeated exposures to PGF2alpha in Ca2+-free medium, initial phasic PGF2alpha-induced force declined less with every exposure than did subsequent tonic force. When the preparations were briefly equilibrated with K+- and Ca2+-rich solution before every exposure to PGF2alpha phasic force did not decline, indicating that phasic force primarily depended on Ca2+ released from intracellular stores. Both beta-blockers failed to relax phasic PGF2alpha-induced force. Thus propranolol and betaxolol are equipotent vasorelaxant drugs in retinal microartery, both probably acting via Ca2+ channel blockade. This activity (that shows no stereospecificity) thus appears to be a more general property of beta-blockers. Microarteries might be more sensitive to this activity than are conductance arteries.

The relaxant action of betaxolol on isolated bovine retinal microarteries.

We investigated the possible effects on retinal blood flow of betaxolol, a beta blocker which is used as antiglaucomatous medication. Ring segments of retinal microarteries were isolated from bovine eyes and mounted in an organ bath for measurement of contractile force. The effects of betaxolol were studied during K(+)-, stretch-, and serotonin-induced contractions, to enable comparison to the effects of the standard beta blocker propranolol and the Ca2+ channel blocker verapamil. Betaxolol relaxed K(+)-induced contractions in a dose-dependent manner. The drug relaxed the phasic part of the K(+)-induced contractions more than the tonic part. Betaxolol had no effect on stretch-induced contractions. The tonic part of the serotonin-induced contractions showed a trend to decrease in response to betaxolol. These highly specific effects of betaxolol resembled the effects of propranolol. Since betaxolol has significantly less membrane stabilizing activity than has propranolol, this activity is not responsible for the relaxant action of beta blockers on retinal microarteries. The action of both beta blockers resembled the action of the Ca2+ channel blocker verapamil.

A rare case of chronic papillary conjunctivitis diagnosed after several years of evolution. Clinical and pathological findings.

A man with a 2.5 year history of chronic papillary conjunctivitis was diagnosed as having "floppy eyelid syndrome". This syndrome, first described in 1981, is characterized by loose upper eyelids that evert readily on elevation of the lid, a chronic papillary conjunctivitis and a soft rubbery tarsus. The condition is resistant to any form of medical treatment but responds well to a horizontal lid shortening procedure. The etiology is unknown but the present report suggests that an abnormality of the structure of the orbicularis muscle may play a role.

Contractile responses of isolated bovine retinal microarteries to acetylcholine.

The contractile responses of isolated and activated bovine retinal microarteries (BRA) (diameter, 204 +/- 4 microns; n = 48) to acetylcholine (ACh) were studied. These responses depended on the nature of the activating agent. The ACh relaxed BRA activated by prostaglandin F2 alpha (PGF2 alpha) and circumferential stretching in a dose-dependent manner but had no significant effect on K(+)-activated BRA. The effects of ACh also depended on the degree of BRA activation: the stronger the PGF2 alpha-induced contractions, the weaker the relaxation produced by ACh. In equivalent PGF2 alpha-induced contractions, the ACh effects were reproducible. The muscarinic antagonist, atropine, reversed the relaxation caused by ACh of PGF2 alpha-activated BRA. Physostigmine, an inhibitor of acetylcholinesterase, did not potentiate or prolong the relaxant action of ACh. Selective removal of the BRA endothelium (by gassing the BRA lumen, checked by scanning electron microscopy) blocked the relaxation caused by ACh of PGF2 alpha-induced contractions and unmasked a constricting action of ACh. This suggests that, in BRA with functional endothelium, the direct constricting effects of ACh on smooth muscle are masked by the more potent dilating activity, mediated by endothelial muscarinic receptors. Acetylcholinesterase was not found in BRA.

Effects of beta-antagonists on contraction of bovine retinal microarteries in vitro.

Contractile responses of bovine retinal microarteries (BRA) (diameter: 198 +/- 5 microns, n = 49) to beta-antagonists, local anesthetics and Ca2(+)-antagonists were studied in vitro. Propranolol (10(-8)-10(-5) M) relaxed K(+)-activated BRA dose-dependently, whereas timolol (10(-8)-10(-5) M) relaxed K(+)-activated BRA only weakly at the highest doses. The relaxation by propranolol was not mediated through interaction with adrenergic nerve endings, since fluorescence histochemistry showed absence of such nerve endings in BRA. In addition, propranolol still relaxed BRA which were treated with 6-hydroxydopamine (6-OHDA), which causes chemical adrenergic denervation. Local anesthetic properties of propranolol had no part in the relaxation: lidocaine (10(-7)-10(-5) M) did not relax K(+)-activated BRA. Verapamil (10(-9)-10(-6) M) relaxed K(+)-activated BRA markedly and dose-dependently. Both verapamil and propranolol relaxed phasic K(+)-induced force more than tonic force. By contrast, they relaxed only the tonic part of serotonin-induced force, and they had no effect on stretch-induced active force. Therefore: 1) propranolol dilates BRA more than does timolol, possibly because of the Ca2(+)-antagonistic properties of the former; 2) beta- and Ca2(+)-antagonists probably spare myogenic autoregulation of blood flow and do not prevent, but could partially reverse, serotonin-induced arterial spasm.

Effect of alpha-1 and beta agonists on contraction of bovine retinal resistance arteries in vitro.

Contractile responses of bovine retinal arteries (BRA) (diameter: 179 +/- 9 micron, n = 25) to high K+, circumferential stretch and adrenergic stimulation were studied in vitro. BRA could be activated by rapid circumferential stretch. Under resting conditions, phenylephrine consistently activated BRA at the highest dose of the drug used (10(-5) M). During K+- and stretch-induced activation, significant contractile responses to phenylephrine appeared at lower doses (respectively, 3.10(-8) and 10(-6) M). Isoproterenol did not relax K+- and stretch-induced contractions. Therefore, (1) BRA probably can autoregulate through a myogenic mechanism on the basis of stretch; (2) during alpha 1 adrenergic stimulation, myogenic autoregulatory responses probably increase; (3) contractile responses to alpha 1 adrenergic stimulation are masked under resting conditions; and (4) BRA may not possess functional beta adrenergic receptors.

Effects of ryanodine on relaxation in isolated myocardium from different animal species.

Relaxation in mammalian ventricular cardiac muscle is sensitive to the prevailing load. This "load dependence of relaxation" (LD) can be demonstrated only when an efficient sarcoplasmic reticulum (SR) is present. To define further the role of the SR in LD, we studied contraction and relaxation in cat, rat and frog cardiac muscle after exposure to ryanodine. Ryanodine is a selective inhibitor of calcium release from the SR. This view was confirmed in the present study in single cardiac rat myocytes with functioning SR. Ryanodine did not affect LD in multicellular mammalian myocardium even though it had already significantly depressed contractility, suggesting that calcium release from the SR plays no role in establishing LD. Calcium accumulation in the SR as a consequence of the inhibited release can account for the late depression of LD in the presence of ryanodine.