Eye Pharmacology

• What is mydriasis?

  Dilated pupil
• What is miosis?

  Constricted pupil
• What is Horner's syndrome caused by?

  Defect in sympathetic nervous supply
• What are the 2 types of muscles in the iris?

  Radial

  Circular
• Circular vs Radial muscles

  Radial

  • sympathetic innervation
  • noradrenaline
  • alpha 1 adrenergic receptor
  • contraction of muscles = dilation of pupil

  Circular

  • parasympathetic innervation
  • acetylcholine
  • M3 muscarinic receptor
  • contraction of muscles = constriction of pupil
• What happens in terms of the radial & circular muscles when the pupil is dilated?

  Radial muscles contracted -> sympathetic 'on'

  Circular muscles relaced -> parasympathetic 'off'
• What happens in terms of the radial & circular muscles when the pupil is constricted?

  Radial muscles relaxed -> sympathetic 'off'

  Circular muscles contracted -> parasympathetic 'on'
• Fill in the blanks

  A) Light

  B) Cornea

  C) Lens

  D) Retina

  E) Focal point

  F) Optic nerve

  
• What are opsins?

  Light-sensitive receptors
• What are the 4 main types of opsins?

  Rhodopsin (rods)

  Long-wave-sensitive opsin 1 ('red' cones)

  Medium-wave-sensitive opsin 1 ('green' cones)

  Short-wave-sensitive opsin 1 ('blue' cones)
• What do rods detect?

  Light
• What do cones detect?

  Colour
• What is rhodopsin made up of?

  Opsin (apoprotein) + chromophore (11-cis-retinal)
• What happens when light hits rhodopsin?

  Photon causes 11-cis-retinal to undergo isomerisation to all-trans-retinal = strutcural change of retinal & rhodopsin -> drives intracellular signalling
• What are the 3 subunits of transducin?

  alpha GTPase

  beta regulatory subunit

  gamma regulatory subunit
• What happens when rhodopsin activates transducin?

  Light activation -> release of GDP & binding of GTP to Gt alpha -> activates downstream signalling -> activation of cGMP phosphodiesterase -> decreased cGMP -> FINISH
• What produces aqueous humour?

  Ciliary body
• How is aqeous humour produced?

  Passive diffusion of solutes down concentration gradients

  Filtration of fluid from fenestrated capillaries into interstitium of ciliary stroma (passive)

  Active secretion of solutes against gradients
• Flow of aqueous humour?

  INFLOW

  Ciliary body -> posterior chamber -> pupil -> anterior chamber

  OUTFLOW

  90% - trabecular meshowrk -> Schlemm's canal -> scleral & episcleral veins (pressure sensitive)

  10% - uveoscleral route
• What is the ciliary body compromised of?

  Muscules

  Epithelia

  Stroma

  Vessels

  Nerves
• What are the 3 types of ciliary muscles?

  Longitudinal -> most external

  Circular -> anterior

  Radial -> intermediate
• What do the longitudinal ciliary muscles do?

  Connect scleral spur & trabecular network anteriorly to choroid sclera posteriorly

  Contraction -> opens trabecular network & Schlemm's canal
• What do the circular ciliary muscles do?

  Contraction -> accommodation
• What do the radial ciliary muscles do?

  Connect longitudinal & circular ciliary muscles
• What are the 2 epithelia in the ciliary body?

  Inner layer -> non-pigmented, adjacent to aqueous humour in posterio chamber

  Outer layer -> pigmented, adjacent to stroma/vessels
• What is the aim of glaucoma drugs?

  Increasing aqueous drainage (increased outflow)

  Reducing aqueous production (decreased inflow)
• Rhodopsin is just another G protein-coupled receptor, with retinal as a light-sensitive drug.
• G protein-coupled receptor signalling cycle

  At rest -> G protein is associated with the receptor (Ga bound to GDP)

  Agonist binding -> confirmational change -> exchange of GDP to GTP & dissociation of receptor, and alpha & beta-gamma subunits -> both a & beta-gamma subunits can interact with molecules to cause a signal -> intrinsic GTPase activity of G-alpha subunit -> cleaves GTP to GDP -> signalling ends (back to rest)
• What are retinoids?

  Drugs related to structure of retinoic acid
• What are the retinoid receptors?

  Nuclear hormone receptors
• What is anisocoria?


  Different sized pupils
• What can cause drug-induced mydriasis? (3)

  L-Dopa

  Anticholingerics

  Cocaine
• How do opiates affect the pupils?

  Constriction (miosis)
• Miosis is a clinically important early diagnostic sign of Novichok poisoning.
• What are ciliary muscles?

  Circular ring of muscle around the lens

  Used for accommodation
• Accommodation makes the lens more convex.
• What NS is active when ciliary muscle is relaxed?

  Sympathetic
• What NS is active when ciliary muscle is contracted?

  Parasympathetic
• What are the receptors on ciliary muscle?

  M3 (muscarinic) -> parasympathetic (ACh) -> contraction

  B2 (adrenergic) -> sympathetic (noradrenaline) -> relaxation
• What happens when you activate Gs in smooth vs cardiac muscle?

  Increases cAMP

  Cardiac -> increased rate & increased force of contraction

  Smooth -> decreased contraction -> relaxation (due to decreased myosin light chain kinase (MLCK in image), as it is being phosphorylated by PKA -> no myosin light chain phosphorylation, so no muscle contraction)