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
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 (ß2
receptors)
4. Enhance aqueous humor formation (ß2
receptors)
5. Inhibit aqueous humor formation (2 receptors)
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
Drugs promoting mydriasis
(pupil dilation)
• Sympathomimetics (things that
stimulate or mimic stimulation of
sympathetic nerves)
• Inhibitors of parasympathetic nervous
system (Atropine)
Nicotinic
Receptor
1 receptor
NE
NE
Granule
Pump NE
Postganglionic
Nerve
(-)
Amphetamine
Axoplasmic Pump
NE
Eye
Cocaine
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 postganglionic nerve damage vs. a defect prior to the postganglionic
nerve (no reaction means postganglionic nerve defect)
– response to amphetamine indicates normal post-ganglionic nerve
Nicotinic
Receptor
1 receptor
NE
Granule
Pump
Postganglionic
Nerve
Eye
NE
(-)
Amphetamine
Axoplasmic Pump
NE
NE
Cocaine
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
Mydriatics
Muscarinic receptor antagonists
• ATROPINE (Atriposol)- (0.5 to 3% solution) to
produce cycloplegia
Muscarinic
Receptor
Nicotinic
Receptor
Ach
Preganglionic
Nerve
Ach
Ach
Ach
Postganglionic
Nerve
Eye
Acetylcholinesterase
Acetate +
Choline
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
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)
Nicotinic
Receptor
1 receptor
NE
Granule
Pump
Postganglionic
Nerve
Eye
NE
(-)
Amphetamine
Axoplasmic Pump
NE
NE
Cocaine
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
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
dorzolamide and brinxolamide
such
as
acetazolamide,
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
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
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
Summary (cont)
• Miotic Agents
– Muscarinic agonist (Pilocarpine,
Acetylcholine)
– Alpha1 adrenergic antagonists (Terazosin)
– Anticholinesterases (Physostigmine)
– Nicotine
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
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)
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
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