BIOSYSTEMS: SEMINARS - milestones, vessels, cil., iprgc, vis. field Flashcards
Summarise the development of the eye following closure of neural tube [ocular milestones #1]
wk 4: closure of neural tube (start); formation of optic vesicles + lens placode (end)
wk 5: formation of lens vesicle + optic cup (start)
wk 6:development of primary lens fibres + optic nerve (start)
wk 7: establishment of hyaloid artery + completion of closure of choroidal fissure (at start)
wk 7-8: migration of precursor cells to primitive neural retina
*tube - placode - vesicles - cup - fibres - nerve - hyaloid - fissure closure - migration precursor cells
What is coloboma? [ocular milestones #2]
- a congenital defect of the eye that occurs due to incomplete closure of the choroidal fissure
Which structures are affected by coloboma? [ocular milestones #2]
Depends on which part of choroidal fissure doesn’t close properly.
If anterior: cornea, iris, ciliary body, lens
if posterior: choroid, retina, optic nerve
What does a coloboma-affected iris look like? [ocular milestones #3]
Characteristic keyhole pupil in inferior region
When does fusion of coloboma start? [ocular milestones #2]
At around week 5 (fusion starts centrally and proceeds outwardly), complete by week 7
List 3 subtypes of coloboma by the structure they affect. [ocular milestones #2]
- Iris coloboma
- Chorioretinal coloboma
- Optic nerve coloboma
What does complete iris coloboma affect? What about partial? [ocular milestones #2]
Complete: affects pigmented epithelium (PE) + stroma
Partial: only affects pupillary margin (only oval-pupil, not keyhole)
When does chorioretinal colboma and what does it affect? [ocular milestones #2]
When posterior part of choroidal fissure won’t close properly.
Affects: RPE, retina, choroid
(also increases risk of retinal detachment)
How does optic nerve coloboma affect the NRR? (ocular milestones #3]
Thinning and absence of NRR in infero-nasal portion
Causes of coloboma? [ocular milestones #2]
Inherited: mendelian (AD, AR, or X) or chromosomal abberations (often with co-morbidities)
Environmental:
- drug use (thalidomide)
- alcohol (foetal alcohol syndrome)
- Vitamin A deficiency
What is Microphthalmia and how can coloboma cause it? [ocular milestones #3]
Abnormally small eyes with abnormalities such as turned eye
Cause: failure to close fissure causes vitreal fluid drainage (vitreal fluid needed for eye development)
Why would a left eye be turning in intermittently in 2 year old px? [ocular milestones #3]
May be due to:
- coloboma assoc. microphthalmia
- other unrelated EOM defect
- CN6 defect
- high hyperopia/anisometropia
Why might the red-eye effect be stronger in photographs for one eye in 2 yo px [ocular milestones #3]
May be due to:
- left eye atrophy of posterior structures, assoc. with chorioretinal coloboma
- retinoblastoma (cancer at posterior retina) - can lead to white pupil reflex
- congenital cataract
What clinical observations could you make/check for in a 2yr old px with turned ey intermittently? [ocular milestones #4]
- ask if during specific task
- check for anisometropia
- check for VA (drop in VA with coloboma)
- check for esophoria/tropia (expect large esotropia for coloboma)
- check for CN palsy (in ocular motility)
- check for APD (afferent pupil defect) (for optic nerve coloboma)
- look at back of eye to check for retinoblastoma
What is the normal average size of the optic nerve head? [ocular milestones #4]
About 1.70mm horizontal, 1.90mm vertical
Describe the clinical representation of optic nerve atrophy [ocular milestones #4]
Manifest as:
- change in colour and structure of optic disk
- with variable degree of visual dysfunction
- ONH = pallor apearance
note: glaucoma is a common cause of optic nerve atrophy
Clinical features of optic nerve hypoplasia? [ocular milestones #4]
Abnormally small ONH, gray-pale disc with double peripapillary ring, vascular tortuosity, thinning of RNFL.
Could be assoc. with hypothalamic/pituitary dysfunction
List and describe the 3 layers of blood vessels (ordered from inner to outer layer) [Blood Vessels #1]
- Tunica intima: single layer of fenestrated endothelial cells (has valves to stop back-flow)
- Tunica media: SMCs allowing for vasoconstriction/dilation
- Tunica adventitia: layer of type 1 collagen and fibroblasts for anchoring
Compare the 2 Blood Ocular Barriers: blood aqueous barrier (BAB) and blood retinal barrier (BRB) [Blood Vessels #1]
BAB: formed by an epithelial barrier located in the Non-pigmented ciliary epithelium and posterior iris epithelium
BRB: located at 2 levels:
outer barrier in RPE - restricts molecule passage to outer segment of photoreceptors
inner barrier in endothelial membrane of retinal vessels - for preserving vessel homeostasis
Both: these layers have “leaky” tight junctions
What artery provides blood supply to the eye? What are its main subdivisions/branches? [Blood Vessels #1]
Ophthalmic artery. Is composed of:
- central retinal artery: supply inner retina
- lacrimal artery
- long posterior ciliary arteries: supply iris + cil. body
- short posterior ciliary arteries: form arterioles in choroid (also supply cil. body)
How do the following affect IOP? A: Systolic b.p B: Systemic b.p C: Obesity: D: Glaucoma E: Normal-tension Glaucoma [Blood Vessels #2]
A: Increased systolic b.p – increase IOP via increased capillary pressure within cil. body
B: Increased systemic b.p – affect episcleral venous pressure
C: Obesity correlated with increased IOP
D: Glaucoma – increased IOP via increased blood volume within cil. body
E: NTG - IOP same
What level of Ocular Perfusion Pressure (OPP) is suggested to increase risk of Glaucoma [Blood Vessels #3]
Low OPP
How does our body compensate/counterbalance for low OPP? Can this system be impaired? [Blood Vessels #4]
A drop in OPP is counter-balanced by autoregulation:
- vasodilation (the vessels release NO) + tissue oxygen extraction
- constant BF + oxygen metabolism maintained
- neuronal function is preserved
What are the biochemical effects of low OPP (ocular perfusion pressure)? [Blood Vessels #4]
- mitochondrial dysfunction
- oxidative stress
- glial cell upregulation
All 3 of these things cause ganglion cell damage and apoptosis
Which portions of the cil. body epithelium produce and reabsorb aqueous? [cil. body #1]
Anterior portion: produces aqueous
Posterior portion: re-absorbs aqueous
What makes up the ciliary stroma? [cil. body #1]
Mainly collagen fibrils and ground substance. Also contains melanocytes and fibroblasts
Describe the parasympathetic innervation pathway for ciliary muscle contraction [cil. body #2]
EW nucleus – CN3 inferior division – cil. ganglion – short post. cil. nerves – cil. muscle
Which part of the trabecular meshwork is draining? Which is non-draining? [cil. body #1]
Posterior = draining Anterior = non-draining
Describe the sympathetic innervation pathway for ciliary muscle relaxation [cil. body #2]
Thalamus/Hypothalamus – Sup. Cerv. Gang. – long cil. nerve – cil. muscle
List the Near triad [cil. body #2]
- Accommodation
- Convergence
- Pupil constriction
Describe the 3 sequential steps in the Macknight-Civan model of Aqueous secretion [cil. body #3]
- Na+ and Cl- are transferred from stroma into PE cell
using: Na+/H+ antiport, Cl-/HCO3- antiport, Na+/K+/2Cl- symport - Solutes pass into NPE cell - through gap junctions
- NPE cell releases Na+ and Cl- into posterior chamber (via Na+/K+ atpase and Cl- channels)
Through which pathway does the majority of aqeuous outflow occur? [cil. body #3]
TM – Schlemm’s Canal – Collector Channels – Aqueous Veins – Episcleral Veins
Effect of increased EVP (episcleral venous pressure) on aqueous outflow? [cil. body #3]
Decreases
How do adrenergic drugs lower IOP? [cil. body #4]
Alpha agonists and Beta antagonists
alpha receptor is coupled to an inhibitory G-protein and the beta receptor is coupled to an excitatory G-protein for the activation of Adenyl Cyclase (AC)
How does pilocarpine reduce IOP? [cil. body #4]
Through ciliary muscle constriction, causing the opening of pores in TM (TM relaxation)
Can combining alpha agonists with beta antagonists have a greater effect on IOP reduction? [cil. body #5]
Yes
What is the effect of the following drugs on IOP? [cil. body #5]:
- Apraclonidine
- Brimonidine
- Timolol
- Betaxolol
- Acetazolamide
- Dorzolamide
All of them decrease IOP. Timolol decreased by the most (33.2%, it is a beta blocker)
What is a likely condition for a px who increases IOP by 4mmHg after 2 minutes of near reading? [cil. body case study]
Progressive Myopia
What are ipRGCs? (Intrinsically photosensitive retinal ganglion cells) [ipRGC #1]
A.K.A ‘melanopsin retinal ganglion cells’
Are a type of rGC that responds to light without rod/cone inputs due to the presence of melanopsin, a light sensitive protein
What is the role of ipRGCs? (ipRGC #1]
Play a role in non-image forming light responses:
- light/dark cycles (sleep-wake cycles)
- pupil light reflexes
- melatonin production
When were ipRGCs discovered? When discovered in humans? [ipRGC #1]
1923 by Clyde Keeler
- noticed mice lacking rods/cones still constricted pupils in response to light
found in humans in 2005
How do ipRGCs cause pupillary light reflex (PLR)? How does the response compare to rods/cones? [ipRGC #2]
ipRGCs project to the pretectum, which is assoc. with PLR
Response is slower than rods/cones (and they require more irradiance than rods/cones too)
How do ipRGCs modulate the circadian clock? [ipRGC #2]
ipRGCs signal (excitatory) to the suprachiasmatic nuclei (SCN) of the hypothalamus, which serves as the circadian clock.
Why is melanopsin required for normal visual processing? [ipRGC #2]
melanopsin increases in baseline firing increase the amplitude and reliability of responses to fast frequency stimuli
What is PIPR and how is it caused by ipRGCs? [ipRGC #3]
PIPR = Post Illumination Pupil Response
- a sustained constriction of more than 30 seconds in response to high intensity light
ipRGCs are maximally sensitive to short-wavelength (blue) light, and they show SUSTAINED FIRING long after light is switched off
How can PIPR be used to monitor and diagnose disease? [ipRGC #4]
- used to monitor glaucoma. PIPR often not affected until late-stage glaucoma
- diagnose AMD. PIPR is impaired in early AMD
List the components of the visual pathway in order [VisField #1]
Retina optic nerve optic chiasm optic tract lateral geniculate body optic radiations primary visual cortex
Which fibres in the retina are crossed? Which are uncrossed? In relation to Visual Pathway [VisField #1]
Nasal fibres = crossed (cross at optic chiasm)
Temporal fibres = uncrossed
List the 4 sections of the optic nerve [VisField #1]
- Intraocular
- Intraorbital
- Intracanalicular
- Intracranial
What conditions may be responsible for the following visual field defects? [VisField #2]:
- Central Scotoma
- Paracentral Scotoma
- Arcuate Defects
- Ceocentral scotoma
- Complete blindness of ipsilateral eye
Central scotoma: Subretinal oedema
Paracentral scotoma: Glaucoma, Oedema
Arcuate defects: Glaucoma
Ceocentral scotoma: Intrinsic optic nerve disease
Complete ipsilateral blindness: Trauma, Compressive tumour, Inflammation
What conditions may be responsible for blind spot enlargement? [VisField #2]
- Compression of nerve fibres
- Drusen
- Myelinated nerve fibres
- Optic nerve sheath meningioma
Describe the dorsal and ventral nucleus of the LGN [VisField #2]
Dorsal Nucleus: relay station for primary afferent visual pathway
Ventral Nucleus: primitive + no visual function in man
Describe the nerve fibre distribution in the LGN [VisField #2]
macula fibres: in dorsal wedge
peripheral fibres: torwards ventral side
superior retinal fibres: in medial horn
inferior retinal fibres: in lateral horn
How common are lesions in the LGN [VisField #2]
Rare
Define Optic Radiation {VisField #2]
axons from the neurons in the LGN. Carries info about the contralateral visual field from the LGN to the primary visual cortex
How is the Optic Radiation divided [VisField #2]
Divided into 3 bundles:
- central bundle - macular nerve fibres
- superior bundle - inferior contralateral visual field (passes through parietal lobe)
- inferior bundle (meyer’s loop) - superior contralateral visual field (passes through temporal lobe)
What visual field defects do the following LGN lesions cause? [VisField #2]:
- Temporal lobe lesion
- Pareital lobe lesion
Temporal lobe lesion: cause contralateral homonymous superior quadrantanopia
Parietal lobe lesion: cause contra-lateral homonymous inferior quadrantanopia
Describe the role of the pituitary gland. Where is it located? [VisField #3]
Regulates thyroid and adrenal glands. Located in the sella turcica just below the mid-optic chiasm
How does pituitary adenoma/tumour affect the visual pathway? [VisField #3]
upwards growing of tumour compresses on the inferior/nasal fibres at the anterior knee of willbrand (causing superior/bitemporal visual defect)
Then extends towards posterior knee and compresses superior/nasal fibres (thus causing inferior/temporal defect)
Non-visual symptoms of pituitary adenoma? {VisField #4]
- loss of body/facial hairs
- loss of appetite
- weight gain
- fatigue
- decreased mental function
- low blood pressure + electrolyte abnormalities
- loss of muscle mass + tone
- stunted growth + delayed puberty
