Mary Waters Flashcards
Define “accommodation”
Accommodation refers t the eyes ability to change its focus from distant to near objects by adjusting the shape of the lens in order to maintain light convergence on the fovea. This process is primarily controlled by the ciliary muscles of the lens.
Outline the pathway of accommodation
Afferent pathway
-Light from nearby object is detected by the retina and processed via phototransduction.
-Signal passes through optic nerve to lateral geniculate nucleus of thalamus and then through optic radiations to visual cortex in occipital lobe.
Efferent pathway
Signals from visual cortex are sent to superior colliculus and pre-tectal midbrain bringing about 3 main responses:
(i) Convergence: Pre-tectal area stimulates occulomotor nuclei –> oculomotor nerves stimulates contraction of left and right medial recti muscles to medially rotate eye.
(ii) Pupillary constriction: Direct stimulation of bilateral Edinger westphal nuclei from cortical neurons –> Parasympathetic fibres arise from the edinger westphal nucleus and travel within CNIII, synapse on the ciliary ganglion –> post ganglionic parasympathetic fibres then synapse on sphincter pupillae to constrict the pupil.
(iii) Lens accomodation: Parasympathetic fibres from E/W also stimulate the ciliary muscles to contract (M3 receptor) –> reduces tension on the zonular fibres of the lens which allow the lens to relax and become more convex which increases its refractive power.
Accomodation reflex is different from pupillary reflex in that in accommodation reflex there is direct stimulation of EW nuclei by cortical neurons, while in pupillary reflex it is the pretectal nuclei that stimulate EW
Describe the production of aqueous humor
Aqueous humor is produced through the transport of ions across two main epithelial layers of the ciliary body: the pigmented epithelium (PE) and the non-pigmented epithelium (NPE). These two cell layers are arranged with the pigmented epithelium (PE) facing the ciliary stroma, while the non-pigmented epithelium (NPE) faces the posterior chamber.
Plasma components from nearby capillaries enter the ciliary stroma via ultrafiltration.
On the basolateral membrane of the PE cells, the Na+/K+/2Cl⁻ co-transporter moves Na⁺, K⁺, and Cl⁻ into the cell. This transporter utilizes the sodium gradient established by the Na+/K+ ATPase pump on the basolateral side of the PE. The Na+/K+ ATPase pump actively pumps sodium (Na⁺) out of the cell, creating a low intracellular sodium concentration, which drives the co-transporter.
Once inside the PE cells, the ions (Na⁺, K⁺, Cl⁻) move toward the NPE layer. Sodium ions (Na⁺) are actively transported into the posterior chamber through the Na+/K+ ATPase pump on the basolateral surface of the NPE.
Chloride (Cl⁻) moves across the NPE membrane and follows its electrochemical gradient. This may occur through chloride channels on the basolateral side of the NPE cells.
Bicarbonate (HCO₃⁻) is produced by carbonic anhydrase in the NPE. Bicarbonate can be exchanged for chloride ions through an HCO₃⁻/Cl⁻ antiporter, which helps to increase the osmotic pressure in the posterior chamber.
The overall effect of this ion transport is the creation of an osmotic gradient that draws water into the posterior chamber, resulting in the formation of aqueous humor.
What is the normal intraocular pressure?
10-20 mmHg
List the 4 main determinants of intraocular pressure
- Rate of aqueous humor production (increased by B2 activation, decreased by alpha 2 activation)
- Rate of aqueous humor drainage–>Outflow resistance/ Episcleral venous pressure
- Aqueous humor volume
name 1 drug that increased aqueous humor production, and 1 that decreases its production
Beta 2 agonists increase production
-Epinephrine
Alpha 2 agonists decrease production
-Brimonidine
Describe 2 drugs that can dilate pupils (Mydriatics)
Pupil dilation achieved through either:
(i) Activation of SNS -> Phenylephrine -> alpha 1 receptors of dilator pupillae
(ii) Blockade of PSNS –> Tropicamide, Atropine –> M3 antagonists on sphincter pupillae –> inhibits constriction –> dilation
Atropine is a cycloplegic as well as a myadriatic and so can paralyse the ciliary muscle which can cause loss of accommodation reflex
Why might pilocarpine be used in the treatment of acute closed angle glaucoma?
Pilocarpine is an M3 receptor agonist
It causes contraction of the ciliary muscle and constriction of the pupil
This opens the iridocorneal angle by pulling both muscles towards the equator of the globe and away from the trabecular meshwork -> this allows for better drainage of aqueous humor.
Describe the mechanism of action of Prostaglandin analogues in the treatment of open angle glaucoma
Latanoprost, Bimatoprost
Reduce resistance to outflow
- Binds to prostaglandin F2-alpha receptors of the ciliary body and trabecular meshwork
-Enhances matrix metalloproteinase activity in trabecular meshwork
-Promotes extracellular matrix remodelling in uveoscleral pathway
-Promotes ciliary muscle relaxion
MOA of Beta blockers in glaucoma
Timolol, Betaxolol
Inhibit production of aqueous humor
Beta-blockers block beta receptors (mainly beta-2) in the ciliary body, reducing cAMP production, which in turn decreases the activity of ion transporters (such as Na+/K+/ATPase and Na+/K+/2Cl- cotransporters), leading to a reduction in aqueous humor production and lowering intraocular pressure (IOP).
MOA of carbonic anhydrase inhibitors in glaucoma
Dorzolamide, Acetazolomide
Inhibition of carbonic anhydrase prevents the production of bicarbonate ions from Co2 and H20.
Since bicarbonate is a key ion involved in producing an osmotic gradient to drag water into the posterior chamber, by blocking its production it reduces the osmotic drive needed for aqueous humor production thereby reducing IOP.
MOA of alpha-2 agonists in glaucoma
Brimonidine
Binds to alpha-2 receptors of the ciliary body which causes reduced activity of adenylate cyclase and subsequently a reduction in cAMP. This reduces the activity of ion/ membrane transporters involved in aqueous humor production. This therefore lowers IOP.
List 4 classes of drugs used to treat open angle glaucoma
(1) Prostaglandin Analogues ( Latanoprost/ Bimatoprost) -> reduces resistance to outflow
(2) Beta blockers (Timolol, Betaxolol) -> Reduces the production of aqueous humour.
(3) Carbonic anhydrase inhibitors (Dorzolomide, Acetazolomide) -> reduces production
(4) Alpha 2 agonists (Brimonidine) -> reduces production
