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Autonomic Innervation of the Eye

Autonomic Innervation of the Eye. Trachte March 4, 2008. Goals. To understand how the sympathetic & parasympathetic nervous systems: affect the eye; how autonomic drugs affect the eye and eyelid; and treatments for glaucoma. Sympathetic Nervous System.

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Autonomic Innervation of the Eye

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  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) • contract superior tarsal muscle to hold eyelid open (1 receptor) • Relax ciliary muscle for distant vision (ß2 receptors) • Enhance aqueous humor formation (ß2 receptors) • 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)

  6. 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

  7. Mydriatics • Alpha1 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

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

  9. 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

  10. Drugs producing miosis Agents preventing acetylcholine degradation • Physostigmine (Isopto eserine), Ecothiophate (phospholine iodide), demecarium (Humorsol), isofluorophate (floropryl) • Alpha1 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)

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

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

  17. 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

  18. 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)

  19. 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

  20. 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

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