Eye

Question 1

What is the purpose of the eyelids?

Answer 1

Protection of the eye
Blink reflex
Ensures front of the eye is lubricated with tear fluid

Question 2

Where is tear fluid produced from?

Answer 2

Lacreal glands above the eye, the tear fluid then drains through canals

Question 3

Describe the part of the eye we can see?

Answer 3

Sclera - white of the eye
Pupil - hole in the middle, controls the amount of light received by the eye
Iris - coloured portion of the eye

Question 4

What is the conjunctiva?

Answer 4

Membrane that covers, protecting the eye. Tear fluid then sits at the front allowing outer surface protection

Question 5

What is the purpose of the cornea?

Answer 5

Circular transparent window at the front of the eye
Ensures the refraction of light as it enters

Question 6

What is the purpose of the anterior chamber?

Answer 6

The anterior chamber is the front part of the eye between the cornea and the iris and provides the aqueous humour.

Question 7

What is the purpose of the aqueous humour?

Answer 7

It provides oxygen and nutrients to the transparent organs within the eye as well as maintaining the intraocular pressure which keeps the eye inflated.

Question 8

Describe the production and supply of the aqueous humour.

Answer 8

To ensure constant intraocular pressure within the eye, turnover is required. It is produced from the ciliary body, it flows across the front of the lens, out through the pupil and the drains into the canal of Schlemm (circular production pathway).

Question 9

Which muscle is the iris composed of?

Answer 9

Smooth muscle which aids pupil response to light.

Question 10

What is the main purpose of the lens?

Answer 10

It is a transparent organ with its primary focus to fine focus the light on to the retina. The lens is held in place by suspensory ligaments which attaches it to the ciliary body which contains smooth muscle which aids fine focusing.

Question 11

Where is vitreous humour found?

Answer 11

In the chamber of the eye and is responsible for absorbing energy, important for protecting the neural retina.

Question 12

What are the two parts of the retina?

Answer 12

The retina is found at the back of the eye and is divided into two parts:
Neural retina which is light sensitive
Retinal pigment epithelium

Question 13

When light enters the eye where is it focused on?

Answer 13

The fovea at the back of the eye due to having the highest visual acuity.

Question 14

Where is the choroid found and what is its function?

Answer 14

It is found behind the retina. It is pigmented ensuring light absorption and highly vascular. Provides a blood supply for the outer layers of the retina.

Question 15

What is the purpose of the optic disk?

Answer 15

This is the point where all the axons meet to form the optic nerve to transmit information to the brain. This is also the point that blood come in supplying the inner retina.

Question 16

Where is the blind spot located?

Answer 16

At the optic disk as they are no light sensitive cells here.

Question 17

What are the two types of smooth muscle controlling pupil size?

Answer 17

Circular smooth muscle (fibres run in a circular fashion) and radial smooth muscle

Question 18

Explain in what circumstances circular muscle contraction occurs.

Answer 18

In response to light, circular smooth muscle contraction occurs stimulated by the parasympathetic nervous system. This causes pupil constriction - restricting the amount of light entering the pupil.

Question 19

Explain in what circumstances radial smooth muscle contraction occurs.

Answer 19

In darkness, radial smooth muscle contraction occurs stimulated by the sympathetic nervous system. This results in the radial fibres becoming shorter leading to pupillary dilation.

Question 20

What is the first point of focusing light?

Answer 20

The cornea which enables the greatest degree of refraction. To ensure the refraction occurs evenly the cornea surface must be very smooth - astigmatism results due to unsmooth cornea.

Question 21

What occurs in laser corrective surgery?

Answer 21

The curvature of the cornea is altered which in turn then changes the plane of focus - how light is focused on to the retina.

Question 22

Explain what is meant by the concept of accommodation.

Answer 22

Accommodation of the eye refers to the eye’s ability to adjust its focus to see objects clearly at different distances. This is achieved by changing the shape and curvature of the eye’s natural lens to bring images into sharp focus on the retina, remember unable to change the curvature of the cornea.

Question 23

Explain the concept of fine focusing in relation to far vision.

Answer 23

For far vision the circular ciliary muscle is relaxed, the intraocular pressure pulls the lens taut (thin and flat) resulting in less curvature and therefore is able to focus parallel light coming from a distant point.

Question 24

Explain the concept of fine focusing in relation to near vision.

Answer 24

For near vision, more curvature is required so the circular ciliary muscle contracts, the suspensory ligaments become slack which enables the lens to become more rounded more refraction to ensure light is focused from a close source. This is mediated under the control of the parasympathetic nervous system which innovates the ciliary muscle of contraction.

Question 25

Is accommodation mediated by the sympathetic or parasympathetic nervous system?

Answer 25

Parasympathetic nervous system innovates ciliary muscle contraction for fine focusing on near vision. Whilst the sympathetic nervous system activation does enable some ciliary muscle relaxation enabling fine focusing on far vision this is mainly mediated by the switching off of the parasympathetic nervous system.

Question 26

How is light reflected on to the fovea?

Answer 26

It presents as upside down and back to front which is then sorted by the brain.

Question 27

What occurs in the condition presbyopia?

Answer 27

The lens becomes less flexible with age, can't focus on near vision as the lens is unable to become as rounded as it once was.

Question 28

What causes the condition myopia?

Answer 28

Myopia also known as short-sightedness occurs as a result of the eyeball being too long so when light becomes in from a distant object it is focused in front of the retina meaning it becomes blurred. Can see close images but not far away.

Question 29

What causes the condition hyperopia?

Answer 29

Hyperopia is when the eyeballs are too short, unable to see near objects and as light is reflected behind the retina. Can't see close images but able to see far away.

Question 30

What is the purpose of the retina?

Answer 30

It is the light sensitive part of the eye which is responsible for visual transduction, converting light energy to electrical signals within neurons.

Question 31

What is the purpose of photoreceptors?

Answer 31

They are responsible for converting light energy to electrical signals.

Question 32

Describe the two different types of photoreceptors.

Answer 32

Rods which are responsible for black and white (grayscale vision) and cones which are responsible for colour.

Question 32

Describe the visual pathway that occurs within the retina.

Answer 32

When light hits the back of the retina photoreceptors both cones and rods are responsible for converting light energy into an electrical synapse. These then synapse with bipolar cells which then synapse with ganglion cells and it is the extended axons of these ganglion cells which then form the fibres of the optic nerve and transmit the electrical signals to the brain. Light enters at the front of the retina and travels to the back which is the opposite direction of visual processing which starts at the back of the retina.

Question 32

Which wavelengths can photoreceptors respond to?

Answer 32

Between 400-700 nM

Question 33

Which other cells are also found in the retina?

Answer 33

Horizontal cells and amacrine cell which are across the retina and are involved with lateral processing.

Question 34

What are the three sections of photoreceptors.

Answer 34

Each contain a outer segment, an inner segment and a synapse.

Question 35

Describe the structure and the function of outer segment of photoreceptors.

Answer 35

Rod photoreceptors have a rod shaped outer segment and cone photoreceptors have an cone shaped outer segment. They consist of flattened, stacked membranous discs. We are unable to replace our photoreceptors and therefore constant turnover is undertaken by the cells of the retinal pigment epithelium which phagocytose discs at one end and new ones form at the other to prevent accumulated damage. These discs contain light absorbing photopigment.

Question 36

What is present in the inner segment of photoreceptors?

Answer 36

Contains the nucleus, mitochondria, ribosomes

Question 37

What occurs at the synapse?

Answer 37

Neurotransmitter is released, photoreceptors synapse with bipolar cells.

Question 38

How many rods and cones do we have in our retina?

Answer 38

In the retina there are approximately 100 million rods and 6 million cones

Question 39

Describe the difference in sensitivity between rods and cones.

Answer 39

Cones have a low sensitivity to light (therefore need bright light for colour vision) therefore day vision is dominated by cones; rods have a high sensitivity to light (required for night vision) night vision is dominated by cones.

Question 40

Describe the difference in location between rods and cones.

Answer 40

Cones are most abundant in the fovea (colour vision); rods are most abundant in the periphery (black and white vision) this is reflected in our vision - colour in our central vision, black and white in our peripheral vision.

Question 41

Describe the difference in the degree of convergence between rods and cones.

Answer 41

Cones in the fovea have little or no convergence – 1:1 ratio of cone to ganglion cell; whereas in the periphery rods are highly convergent – many rods (up to 100) feed into one ganglion cell

Question 42

What is the result of differences in convergence between cones and rods?

Answer 42

In the central region within the fovea due to the absence of convergence of cones, this provides a high resolution image as the electrical signalling of one photoreceptor then transmits to one bipolar cell and one ganglion cell. But in the periphery hundreds of rods can feed into one ganglion cell meaning there is lower visual acuity (peripheral vision is more blurred) but has a higher sensitivity as there is a wider receptive field.

Question 43

Define visual acuity.

Answer 43

Visual acuity (VA) is a measure of the ability of the eye to distinguish shapes and the details of objects at a given distance

Question 44

Where is visual acuity the highest and why?

Answer 44

Visual acuity in the fovea is highest in this area giving fine resolution of the image. This is due to: – More cones – 1:1 coupling – Lateral inhibition so when one photoreceptor is stimulated it switch the next one off allowing the distinguishment of edges – Other areas of the retinal are moved aside here, so light doesn’t travel through other layers of the retina

Question 45

What is the peripheral vision most sensitive to?

Answer 45

Movement Flashes of light

Question 46

Which part of the photoreceptor is responsible for signal transduction?

Answer 46

Photoreceptors contain photopigments in the outer segment membranes, which are able to capture the light which is the first step in signal transduction. The photopigment consists of a protein known as opsin and retinal which is a chromophore which is the molecule that actually absorbs the light.

Question 47

What type of protein is opsin?

Answer 47

A GPCR with the ligand being retinal which is derived from Vitamin A with deficiency of Vitamin A leading to night blindness.

Question 48

What are the four types of photopigment?

Answer 48

There are 4 photopigments – one in rods (rhodopsin, which is sensitive to all wavelengths of light) and 3 in cones, sensitive to red, green and blue light

Question 49

How does visual transduction begin?

Answer 49

It starts with the absorption of light from the retinal. This induces a shape change within retinal from 11-cis-retinal with a bend to all-trans-retinal. This is the ligand for opsonin so this change in retinal shape induces a conformation change within the GPCR causing a signalling cascade.

Question 50

Describe the signalling cascade for photoreceptors in the dark.

Answer 50

The outer segment of the photoreceptor contains a cGMP-gated cation channel. In the dark cGMP levels are high due to the action of guanylate cyclase converting GTP to cGMP. When cGMP binds this opens the cation channel, allowing sodium influx causing depolarisation to around -40mV. This then induces the opening of the voltage gated calcium channels within the synaptic terminal enabling the influx of calcium into the cell and then calcium mediated exocytosis of neurotransmitters. Therefore in the dark, the photoreceptor is depolarized and is releasing neurotransmitter.

Question 51

Describe the signalling cascade for photoreceptors in the light.

Answer 51

Light comes in and is absorbed by retinal causing a change in shape from 11-cis-retinal to all-trans-retinal this then induces a conformation change within the GPCR activating its G-protein Transducin. This then activates phosphodiesterase which in turn degrades cGMP causing a close of the cGMP-cation channel. This prevents sodium influx causing a hyperpolarisation of the membrane potential, calcium channels are closed, decreasing neurotransmitter release. Therefore in the light, the photoreceptor is hyperpolarized and neurotransmitter release decreases.

Question 52

What is the neurotransmitter released in response to phototransduction?

Answer 52

Glutamate

Question 53

How are we able to detect different responses to light?

Answer 53

The brighter the light the less neurotransmitter is released and hence this response is graded accordingly.

Question 54

How does signal termination occur regarding photoreceptors?

Answer 54

Once activated the photoreceptors become bleached and they remain unresponsive until the recycling of retinal has occurred. This then terminates the signal and is mediated by enzymes converting all-trans retinal back into 11-cis retinal.

Question 55

Does depolarisation/hyperpolarisation of retinal cells mimic that of photoreceptors?

Answer 55

No whilst in response to light this causes hyperpolarisation in photoreceptors, in retinal ganglion cells they become activated causing transmission of information to the brain. Whereas in the dark although photoreceptors are depolarised, there is hyperpolarisation in the retinal cells inhibiting neurotransmitter release.

Question 56

What are the three types of opsonins?

Answer 56

Blue, red and green that are all sensitive to different wavelengths of light including their colour which crucially enables us to see a range of colour - for example seeing green will stimulate all three cones. Seeing yellow light for example stimulates both green and red cones. The colours relate to the photopigment which they contain.

Question 57

How does colour blindness occur?

Answer 57

When we are lacking one of the cones and hence this then changes our perception of light.

Question 58

Describe the visual pathways.

Answer 58

Essentially a cross over with both eyes. Light from the right visual field goes to the left side of the eye and light from the left visual field goes to the right side of the eye. Left side of the retina in both eyes goes to the left side of the brain. Right side of the retina in both eyes goes to the right side of the brain. Retinal ganglion cells travel by the optic nerve to the thalamus called the lateral geniculate nucleus which is where synapse occurs, then travels to the occipital lobe where processing occurs.

Question 59

What are the drug classes used to treat glaucoma?

Answer 59

- Prostaglandin analogues – β-blockers – Carbonic anhydrase inhibitors – α2 -agonists – Muscarinic agonists

Question 60

What is the main aim of treatment for glaucoma?

Answer 60

All drugs used in the treatment of glaucoma work by decreasing the intraocular pressure hence slowing the progression of the disease and prevent the retinal ganglion cells from dying and to decrease the loss of visual field.

Question 61

How is the ciliary body attached to the lens?

Answer 61

By the lens zonules

Question 62

What secretes the aqueous humour?

Answer 62

Ciliary processors into the posterior chamber between the iris and the lens and then flows out through the pupil by the pupillary margin.

Question 63

What is the purpose of the aqueous humour?

Answer 63

Aqueous humour supplies nutrients to and removes waste products from the avascular organs of the anterior eye (lens and cornea) It is produced at a rate of 2-3µl / min

Question 64

How does the aqueous humour leave?

Answer 64

70-90% leaves by the conventional pathway which is via the trabecular mesh work and into the canal of schlemm. 10-30% leaves by the unconventional pathway in which the aqueous humour flows out via the intercellular spaces between the ciliary muscle fibres, the choroid and out via the sclera. This component may be greater for patients with glaucoma.

Question 65

What happens in primary intraocular glaucoma regarding the aqueous humour?

Answer 65

Usually the rate of production of aqueous humour matches the rate of outflow, however in primary intraocular glaucoma there is decreased outflow of aqueous humour and so there is increased intraocular pressure.

Question 66

How can drugs used in the treatment of glaucoma reduce intraocular pressure?

Answer 66

Either by increasing outflow or reducing production of aqueous humour.

Question 67

Describe the ciliary epithelia.

Answer 67

The ciliary epithelia consists of two layers of epithelial cells, one of which is pigmented and the other not. The ciliary processors are protrusions of the pigmented layer of the ciliary epithelia, increasing the surface area. Th pigmented layer contains melanin granules and the cells contain gap and tight junctions allowing cross talk and substance control between the two layers.

Question 68

What are the main ions that move across the ciliary epithelia from the blood into the aqueous humour?

Answer 68

Sodium Chloride Bicarbonate Water moves through aquaporins in the membrane This results in the constant production of aqueous humour which is an active process.

Question 69

Describe the ion channels present for aqueous humour secretion.

Answer 69

Na+/K+ ATPase is involved present, sodium ions and moving outwards and potassium move inwards. Na+ movement is balanced by the movement of anions. Carbon dioxide and water is transferred to make bicarbonate together with hydrogen ions by the action of carbonic anhydrase. These ions are then efflux from the cell. B2 adrenergic receptor is present, upon noradrenaline binding this stimulates the sodium/potassium ATPase - this will then increase the production of aqueous humour.

Question 70

Describe the pharmacological control of aqueous humour secretion.

Answer 70

When stimulated by Noradrenaline on the B2 adrenergic receptors this causes an increase in aqueous humour secretion - this goes on to increase the activity of the sodium/potassium ATPase hence increasing the production of aqueous humour. However stimulation of the a2 adrenergic receptors present on the pre-synaptic terminal then reduce cAMP activity, resulting in the closure of calcium ion channels and therefore calcium mediated exocytosis is reduced. Inhibition of carbonic anhydrase then results in a decrease in aqueous humour production.

Question 71

How do beta blockers work in decreasing the production of aqueous humour?

Answer 71

Antagonise B2 adrenergic receptors therefore causing a reduction in aqueous humour production as the sodium/potassium ATPase activity is then reduced.

Question 72

What are the examples of B2 adrenergic drugs used in the treatment of glaucoma?

Answer 72

Timolol (non-selective β-blocker, inhibiting B1 and 2) Carteolol (non-selective β-blocker; also has intrinsic sympathomimetic activity therefore reducing side effects) Betaxolol (more selective for β1 receptors, less efficient)

Question 73

What are some of the side effects associated with beta blockers?

Answer 73

Ocular – include stinging, dry eye, itching, pain, erythema, corneal disorders although may be due to the preservatives – Administered topically, but can cause systemic side effects * Include bradycardia and breathlessness * Contraindicated in bradycardia and heart block

Question 74

Which a2 agonists are licensed for glaucoma?

Answer 74

Reduce the amount of noradrenaline released: Brimonidine Apraclonidine

Question 75

What are some of the carbonic anhydrase inhibitors licensed for glaucoma?

Answer 75

Acetazolamide (not topical) Dorzolamide Brinzolamide

Question 76

How does pupil size affect aqueous outflow?

Answer 76

Aqueous outflow via the trabecular meshwork is: – Facilitated by constriction of the pupil, as the iris muscle will be stretched out keeping the angle open – Inhibited by dilation of the pupil – Facilitated by contraction of the ciliary muscle, circular muscle moves inwards pulling the area more taut, which helps with the flow of aqueous humour.

Question 77

Describe how the iris and the ciliary muscle is innervated.

Answer 77

The parasympathetic nervous system stimulates the the circular muscle, this is by acetylcholine acting on muscarinic receptors causing pupillary constriction. Whereas the sympathetic nervous system stimulates the radial muscle to contract, causing pupil dilation and this is mediated by noradrenaline acting on a1 adrenergic receptors. The ciliary smooth muscle is innervated by parasympathetic nervous system causing the release of acetylcholine and contraction via muscarinic M3 receptors.

Question 78

How do muscarinic agonists work?

Answer 78

Pilocarpine, the only licensed muscarinic agonist works by acting on the M3 receptors and is a parasympathomimetic causing contraction of the circular smooth muscle resulting in pupil constriction. This pulls the area more taut resulting in the facilitation of the flow of aqueous humour. However there are numerous side effects when using muscarinic agonists – mainly ocular eg. Blurred vision in addition to systemic side effects. Used infrequently.

Question 79

How do prostaglandin analogues work?

Answer 79

Analogues of PGF2α; act at PGF receptors (exception bimatoprost) Decreases intraocular pressure by mainly by increasing (>2X) aqueous outflow via the uveoscleral pathway Most recently introduced therapy for POAG –usually the initial therapy in POAG and currently the most frequently used drug to lower IOP Increase extracellular matrix degradation within the sclera therefore increasing the outflow of aqueous humour through the intercellular pathways in order to decrease intraocular pressure.

Question 80

What are some examples of prostaglandin analogues used in the treatment of glaucoma?

Answer 80

Latanoprost Travoprost Bimatoprost These are usually the initial therapy for glaucoma

Question 81

What are some of the side effects of prostaglandin analogues?

Answer 81

* Conjunctival hyperaemia (bloodshot eyes), foreign body sensation, ocular irritation These are due to the drugs themselves and not the excipients * Eyelash lengthening, thickening, hyperpigmentation * Iris hyperpigmentation (11 - 23% of patients) (most common with green-brown irises)