Workshop: Autonomic Nervous System Using the Eye PDF

MD MedProg MEDI-12-201 Week 1 Workshop: Autonomic Nervous System Using the Eye as a Model to Examine Drug Effects on the Autonomic Nervous System Objectives After completing this workshop, students will be ale to: 1. Describe the effect of an...

MD MedProg MEDI-12-201 Week 1 Workshop: Autonomic Nervous System Using the Eye as a Model to Examine Drug Effects on the Autonomic Nervous System Objectives After completing this workshop, students will be ale to: 1. Describe the effect of an adrenergic agonist, sympathomimetic, on the eye 2. Describe the effect of an adrenergic antagonist, sympatholytic, on the eye 3. Describe the effect of a cholinergic muscarinic agonist, parasympathomimetic, on the eye 4. Describe the effect of a cholinergic muscarinic antagonist, parasympatholytic, on the eye Introduction Both the parasympathetic and the sympathetic branches of the autonomic nervous system innervate the eye and are involved in the following: Regulating the amount of light entering the eye Focusing the image on the retina Regulating intra-ocular pressure Figure 1: Structure of the eye Physiology and Anatomy of the eye Light passes through the cornea and the papillary aperture (pupil) and is focused onto the retina by the lens. The retinal image is then sent to the optic centres of the brain via the optic nerve. The amount of light entering the eye and reaching the lens and retina is controlled by the smooth muscle of the iris which regulates the size of the pupillary aperture (Figure 1). Light is focused by the curvature of the lens, which has a variable focal length enabling both near and distant images MD MedProg MEDI-12-201 Week 1 Workshop: Autonomic Nervous System to be focused onto the retina. This is called the accommodation reflex. The curvature and hence focal length of the lens is controlled by the smooth muscle of the ciliary body Smooth muscles of the eye There are two types of smooth muscle controlled by the autonomic nervous system, multi-unit and single unit (also known as visceral smooth muscle). Single unit muscle fibres are connected electrically via many gap junctions and contraction spreads over the muscle sheets (eg. gastrointestinal smooth muscle). In contrast, multi-unit muscles as found in the eye have a greater nervous innervation and the muscle fibres have few gap junctions allowing the fibres to function independently allowing greater nervous control for fine movements. [A] Control of pupillary size - the iris has two sets of smooth muscle. (i) The papillae constrictor smooth muscle is arranged circularly around the aperture and constriction reduces pupil size (myosis or miosis). This muscle is innervated by the 3rd cranial nerve which releases acetylcholine (Ach, parasympathetic nerve), activating muscarinic receptors and causing constriction. (ii) The radial dilator smooth muscle has fibres that radiate out from the pupil. This muscle is innervated by sympathetic nerves that release noradrenaline (NA) which causes contraction via α1-adrenoceptors resulting in increased pupillary size (mydriasis). Q1. Using your knowledge of the structure and function of the eye, consider what effects the following drugs may have on the size of the pupil. (i) Muscarinic agonist (ii) Muscarinic antagonist (iii) Acetylcholinesterase inhibitor MD MedProg MEDI-12-201 Week 1 Workshop: Autonomic Nervous System (iv) α1-adrenoceptor agonist (v) A combination of a muscarinic antagonist and an α1-adrenoceptor agonist (vi) Cocaine (inhibits NA re-uptake into the sympathetic nerve) [B] Lens shape and the accommodation reflex The lens focuses the light on the retina and its focal length is controlled by the ciliary muscle which is attached to the lens by fibre-like suspensory ligaments (Figure 2). Ciliary smooth muscle - Similar to the iris muscle, the ciliary muscle is innervated by parasympathetic nerves which have a dominant control of the muscle. Acetylcholine causes contraction of the ciliary muscle thereby reducing tension on the ligaments and the lens becomes more spherical and adapted for near vision. The muscle also receives some sympathetic nerves which relax the ciliary muscle via NA, the activation of β2-adrenoceptors adapting the lens for far vision. Q2, What effect would a muscarinic antagonist have on your ability to focus on near and far objects? [C] Vitreous and aqueous fluids (humors) The main body of the eye contains vitreous fluid which contains polysaccharides and proteoglycans giving it a gel-like consistency. At the front of the eye, the cornea and the lens are non-vascular which allows light to pass through without distortion, and these tissues are provided with nutrients by the aqueous fluid found between the lens and the cornea. Normally, aqueous fluid flows from behind the iris (posterior chamber, Figure 2), where it is formed by the epithelial cells of the ciliary body, to the front of the iris (anterior chamber) where it drains through a meshwork of MD MedProg MEDI-12-201 Week 1 Workshop: Autonomic Nervous System small channels or trabeculae into the Canal of Schlemm. This empties the fluid into a thin lymphatic like vessel that ultimately empties into the venous system via the ciliary veins. This aqueous fluid should not be confused with tears, which are formed outside the eye. The production and movement of aqueous fluid is influenced by the autonomic nervous system both directly and indirectly. Production of the aqueous fluid by the ciliary body is influenced by the sympathetic nervous system with NA activating β2-adrenoceptors to stimulate secretion. Drainage of the fluid via the trabeculae can also be affected by contraction of the iris smooth muscle which may occlude the trabeculae in some susceptible individuals. Figure 2: Pathway of aqueous fluid flow Dysfunction of the trabecular meshwork/Schlemm’s canal may result in increased resistance to the flow of aqueous fluid and increased intraocular pressure. This is thought to be one pathological mechanism that causes ganglion and support cells of the retina to die, leading to damage of the optic nerve, and giving rise to the condition known as glaucoma. There is also another minor drainage route for the aqueous fluid via the uveoscleral pathway that drains into the sclera and the ultimately the lymphatic system. Glaucoma Glaucoma is characterised by damage to the optic nerve. It is closely associated with a pathological rise of intraocular pressure. If left untreated this damage causes blindness, which is irreversible. There are chronic and acute forms of this disease. MD MedProg MEDI-12-201 Week 1 Workshop: Autonomic Nervous System Chronic open angle glaucoma (90% of glaucoma cases) – with increasing age (above 45y) the trabeculae can become flaccid and there is a reduced drainage of aqueous fluid into Schlemm’s canal, resulting in an accumulation of fluid and increased intraocular pressure. Acute narrow angle glaucoma – a sudden rise in intraocular pressure can result from an occlusion of the trabeculae by the radial dilator muscle. This may be caused by a narrow posterior chamber or by some drugs that cause pupil dilation making it more likely that the muscle will occlude the entrance to the trabeculae meshwork. Q3. With your knowledge of the mechanisms controlling the functions of the eye, consider the types of drug you think could be used to treat glaucoma. What effects would the following types of drug have on intraocular pressure and why? (i) β-adrenoceptor agonist (ii) β-adrenoceptor antagonist (iii) muscarinic agonist (iv) muscarinic antagonist (v) acetylcholinesterase inhibitor