Agneta Mandahl

Substance P-immunoreactive nerve fibres in the anterior segment of the rabbit eye

SummarySubstance P-immunoreactive nerve terminals were found in several locations in the anterior segment of the rabbit eye. In the iris they occurred in the sphincter muscle and were randomly distributed in the iris stroma with some fibres running close to the dilator muscle. In the ciliary body these immunoreactive elements were few and occurred within bundles of nerve fibres, while in the ciliary processes they were more numerous with a predominantly subepithelial location. Blood vessels in the anterior uvea were often surrounded by substance P-immunoreactive fibres. No substance P-fibres were found in the cornea, while the sclera contained very few such elements.Using conventional in vitro techniques it was found that the sphincter pupillae muscle of the iris responded to electrical stimulation with a contraction that was resistant to cholinergic and adrenergic blockade, but was inhibited by the neuronal blocker tetrodotoxin. This indicates the existence of a non-cholinergic, non-adrenergic neuronal mediator of the contractile response. Exogenously applied substance P produced a long-lasting contraction of the spincter muscle, an observation compatible with the view that substance P is the noncholinergic, non-adrenergic neurotransmitter involved.

Effects of the substance P antagonist [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP on miosis caused by echothiophate iodide or pilocarpine hydrochloride

The anticholinesterase agent echothiophate iodide (EI) and the cholinergic agent pilocarpine hydrochloride (pilocarpine), drugs commonly used in glaucoma therapy, cause miosis in rabbits as well as in man. In rabbits the miotic effect decreases after a few days of treatment, a phenomenon possibly due to a drug-induced decrease in the number of muscarinic receptors. However, the muscarinic pupillary contraction caused by stimulation of the retina with light is intact. In this investigation the miosis caused by the doses of EI was found to be very resistant to muscarinic or nerve blockade but inhibited by the substance P (SP) analog [D-Arg1,D-Pro2,D-Trp7,9, Leu11]SP, which seems to be a SP/SPLI blocker in the rabbit pupillary sphincter. Miosis caused by pilocarpine was partly inhibited by muscarinic blockade and partly by the SP blocker. In eyes treated with EI topically twice daily for three weeks, SP or the red pepper extract capsaicin, a releaser of SP-like immunoreactivity (SPLI), had less miotic effect than in control eyes. Capsaicin caused more pronounced miosis in eyes treated with topical pilocarpine for three weeks than in controls. The radioimmunoassay technique did not reveal a significant change in the amount of SPLI in the retinas or iris-ciliary bodies from EI-treated eyes as compared with the controls. It is concluded that, besides cholinergic miosis, EI causes non-muscarinic miosis, probably by release of SP or a related substance and that pilocarpine may have similar effects.

Colour vision and side-effects during treatment with methazolamide.

The retina contains Na+K+-ATPase and carbonic anhydrase (CA), enzymes that regulate ion fluxes across cell membranes of photoreceptors. Since inhibition of retinal Na+K+-ATPase by digitalis impairs colour vision, we wanted to find out whether this also occurs after inhibition of CA. In a double-masked crossover study with placebo, 14 male volunteers were given 50 mg q.i.d. of the CA inhibitor methazolamide for 2 weeks. A disturbance of colour discrimination was observed in 8 of the 14 subjects, in the classification phase of Lanthony New Color Test. The presence of the disturbance was not significantly correlated to the degree of acidosis or to other side-effects. Its mechanism could be interpreted as a specific effect of CA inhibition in the retina (or the visual cortex) calculated to more than 99.9%.

Hypertonic saline test for ophthalmic nerve impairment

Abstract. In order to compare the accuracy of methods for testing ocular surface sensitivity (e.g. function of the first branch of the trigeminal nerve) three different methods were compared in patients with unilateral acoustic neurinomas. The three methods 1) hypertonic (3%) saline in the conjunctival sac (apparently not previously described in the literature) 2) esthesiometer (Cochet & Bonnet) touching of the cornea, and 3) touching the cornea with a cotton wool wisp, was found to reveal reduced ocular surface sensitivity on the neurinoma side in 50% (hypertonic saline), 23% (esthesiometer) and 14% (cotton wool wisp) of cases, respectively. With McNemars test for comparing test methods the 3% saline test proved significantly more sensitive than the cotton wool wisp test (p <0.05), but not significantly more sensitive than the esthesiometer test (p> 0.10). The advantage of the 3% saline test, apart from its high sensitivity, is that it does not require sterilization of any equipment as is the case for the esthesiometer nor, in contrast to the methods using corneal or conjunctival touch, does it require perfect visual control by means of a magnifying glass in order to be performed accurately, and it is not affected by visual stimuli. It should therefore be the preferred test of assymetry in ophthalmic nerve function.

Effects of substance P on regional ocular blood flow, intraocular pressure and blood‐aqueous barrier in rabbits

Abstract. The effect of intracameral injection of 1.0 μg of substance P (SP) on the regional ocular blood flow in albino rabbits was investigated by a method using radioactively labelled microspheres. The mean ciliary blood flow in SP‐treated eyes was 0.163 ± 0.006 g/min and in the control eyes 0.107 ± 0.004 g/min. The flow increase was 72 ± 22%. The mean difference was 0.056 ± 0.005 g/min (P < 0.01, n = 11). Infusion of 25–40 μg of substance P into one common carotid artery over 20–45 min caused a rise in intraocular pressure of 22.5 ± 1.5 cm H2O in the ipsilateral eye and of 1.6 ± 0.2 cm H2O in the contralateral one. The mean difference was 19 ± 5.3 cm H2O (P < 0.05, n = 4). The protein concentration of the aqueous humour on the ipsilateral side was higher than on the contralateral one, and there was marked extravasation of intravenously injected Evans blue in the ciliary processes in the ipsilateral eyes. Extravasation of Evans blue in the ciliary processes and a rise in intraocular pressure also occurred in two rabbits which were given in intravenous injection of SP (0.37 or 3.4 mg). It is concluded that in rabbits SP tends to increase the intraocular pressure and to cause a breakdown of the blood‐aqueous barrier and that the increase in ciliary blood flow caused by SP may play a role in these mechanisms.