1. Autonomic Innervation of the Eye Trachte March 4, 2008

2. Goals To understand how the sympathetic & parasympathetic nervous systems: –affect the eye; –how autonomic drugs affect the eye and eyelid; and –treatments for glaucoma.

3. Sympathetic Nervous System 1. mydriasis- contract pupillary dilator muscle (  1 receptor) 2.contract superior tarsal muscle to hold eyelid open (  1 receptor) 3.Relax ciliary muscle for distant vision ( ß 2 receptors) 4.Enhance aqueous humor formation ( ß 2 receptors) 5.Inhibit aqueous humor formation (  2 receptors)

4. Parasympathetic Nervous System Actions focus eye for near vision (ciliary muscle contraction) constrict pupil (miosis)-(pupillary sphincter contraction) Enhance drainage of aqueous humor (trabecular meshwork & canal of Schlemm) All of these effects mediated by muscarinic receptors

5. Drugs promoting mydriasis (pupil dilation) Sympathomimetics (things that stimulate or mimic stimulation of sympathetic nerves) Inhibitors of parasympathetic nervous system (Atropine)

7. Mydriatics Agents releasing norepinephrine NICOTINE activates nicotinic receptor (also activates parasympathetics to produce miosis, which is the more common reaction) Cocaine blocks axoplasmic pump to increase norepinephrine concentrations in vicinity of adrenergic receptors –2 - 4% solution used to diagnose simple anisocoria vs Horner ’ s syndrome –no effect of cocaine indicates sympathetic dysfunction (if nerves were intact, cocaine would dilate pupil) Amphetamine reverses axoplasmic pump –hydroxyamphetamine (0.1% solution) used to diagnose post- ganglionic nerve damage vs. a defect prior to the postganglionic nerve (no reaction means postganglionic nerve defect) –response to amphetamine indicates normal post-ganglionic nerve

9. Mydriatics Alpha 1 adrenergic stimulants PHENYLEPHRINE (mydrifrin) is a drug used in eye drops to dilate pupil –2.5% to 10% solution used to produce mydriasis –also reverses ptosis in Horner ’ s Syndrome Epinephrine (Epitrate) 0.5 to 2% solution to treat glaucoma –increases aqueous humor outflow

11. Mydriatics Muscarinic receptor antagonists ATROPINE (Atriposol)- (0.5 to 3% solution) to produce cycloplegia

13. Drugs producing miosis Nicotine activates parasympathetic nerves Muscarinic agonists such as Pilocarpine (Pilocar), acetylcholine (Miochol) –Pilocarpine used as 2% solution –1% solution to differentiate IIIrd nerve palsy from “ Atropinic ” mydriasis –If pilocarpine is active (produces miosis) then the defect must be in the nerve

15. Drugs producing miosis Agents preventing acetylcholine degradation Physostigmine (Isopto eserine), Ecothiophate (phospholine iodide), demecarium (Humorsol), isofluorophate (floropryl) Alpha 1 receptor antagonists –TERAZOSIN-not used to treat eye disease but can have ocular side effects Norepinephrine depleting agents- Reserpine (Serpasil)- have the potential of causing ocular side effects (miosis; ptosis)

17. Drugs for Treatment of Glaucoma ß Blockers –Timolol (Timoptic); Betaxolol (Betoptic); Carteolol (Ocupress); Levobunolol (Betagan); Metipranolol (Optipranolol)- they decrease aqueous humor formation Muscarinic Receptor Agonists- –Pilocarpine (Pilocar)- enhances aqueous humor drainage through trabecular meshwork & canal of Schlemm Anticholinesterases- –Physostigmine (Isopto eserine), Ecothiophate (Phospholine iodide)- enhances aqueous humor drainage through trabecular meshwork & canal of Schlemm

18. Drugs for Treatment of Glaucoma Alpha2 Agonists- –Apraclonidine (Iopidine) and Brimonidine (Alphagan)- reduce aqueous humor formation Epinephrine (Epinal) or Dipevefrin (Propine) – Primarily increase aqueous humor outflow but also suppress production Most common current treatment is the prostaglandin derivative, Latanaprost (Xalatan) –It increases uveo-scleral outflow of aqueous humor (flow through the ciliary muscle) –Other prostaglandins include: travaprost (Travatan); bimatoprost (Lumigan); Unoprostone (Rescula) carbonic anhydrase inhibitors such as acetazolamide, dorzolamide and brinxolamide

20. Drugs used to treat ptosis disruption of sympathetic innervation of superior tarsalis muscle of the eye lid (Horner ’ s Syndrome)- can reverse with Phenylephrine skeletal muscle weakness caused by myasthenia gravis (antibodies to nicotinic receptor) injury to, or malfunction of, oculomotor nerve Edrophonium (Tensilon)- anticholinesterase that reverses drooping caused by myasthenia gravis

23. Muscle spasms Strabismus (deviation of the eyes) & Blepharospasm (spasm resulting in closed eyelids) Can treat problems caused by muscle spasms with botulinum toxin (Botox) –inhibits acetylcholine release from somatic nerves –suppression of acetylcholine release can relieve a muscle spasm causing the strabismus or blepharospasm

25. Summary Mydriatic Agents –  1 agonist, phenylephrine –Muscarinic antagonist, Atropine –Agents releasing norepinephine (amphetamine) –Agents preventing norepinephrine uptake into the nerve (cocaine) –These can all precipitate closed angle gluacoma

26. Summary (cont) Miotic Agents –Muscarinic agonist (Pilocarpine, Acetylcholine) –Alpha1 adrenergic antagonists (Terazosin) –Anticholinesterases (Physostigmine) –Nicotine

27. Summary (cont) Tests for intact sympathetic nervous system –Cocaine pupil dilation if the nerves work Lack of pupil dilation indicates defect in innervation –Amphetamine Pupil dilation if postganglionic nerve is present and functional

28. Summary (cont) Treatments for Glaucoma –Agents enhancing aqueous humor outflow Muscarinic agonists (pilocarpine) Prostaglandins (Latanaprost) Epinephrine –Agents suppressing aqueous humor production ß adrenergic antagonists (Timolol)  2 adrenergic agonists (Aproclonidine) Carbonic anhydrase inhibitors (Acetazolamide)

29. Summary (cont) Ptosis –Characteristic of sympathetic nerve disruption Superior tarsalis muscle holds eyelid open –Can be caused by other conditions involving skeletal muscle dysfunction or III nerve palsy Myasthenia gravis Botulinism Occulomotor palsy

30. Summary (cont) Muscle spasms (blephorospasm or strabismus) can be treated with botulinum toxin to relax the skeletal muscle Botulinum toxin acts to suppress acetylcholine release from nerves