BS - Genetics of Eye Diseases - Week 3 Flashcards
Do AMD or glaucoma have a genetic component?
Yes, they both do.
Name the 6 mendelian inheritance patterns.
Autosomal recessive Autosomal dominant X-linked recessive X-linked dominant Codominant Mitochondrial
Name 2 common genetic diseases in school-aged children.
Strabismus
Congenital Nystagmus
Is the prevalence of myopia very high, medium, or low in the general population?
Very high in the general population
What is the prevalence of myopia like in Aisan populations compared to others?
Significantly higher, up to 90%
What is the likely inheritance pattern of myopia (2)?
It can be mendelian, but more often inherited as a complex trait.
What percentage of congenital cataracts have a genetic cause?
50%
Mutations of genes controlling what mechanisms lead to cataracts (4)?
Lens development (PAX6) Lens crystallins (CRY) Gap junctions (Cx43) Aquaporins
What is the 2nd leading cause of congenital vision loss?
Optic nerve hypoplasia
What are the risk factors for optic nerve hypoplasia (7)? What percentage of cases do not have these risk factors?
Preterm birth Alcohol Quinine (malaria) Phenytoin (siezures/cardiac problems) Maternal diabetes Congenital cytomegalovirus infection LSD consumption 70% do not have the above risk factors
What are three symptoms of optic nerve atrophy?
Vision loss
Poorer colour vision
Nerve lost tissue, pale
Name the two forms of optic nerve atrophy, and their inheritance pattern.
Optic atrophy 1 - autosomal dominant
Lebers hereditary optic atrophy - mutations in mitochondrial DNA
What are the inheritance patterns most colour vision deficiency conditions?
X-linked recessive
Name one of the most common retinal degeneration conditions.
Retinitis pigmentosa
Define retinitis pigmentosa.
A group of many forms of inherited retinal dystrophy, or degeneration.
Mutations to proteins in what 7 mechanisms would result in retinitis pigmentosa?
Phototransduction cascade Vitamin A metabolism Cell-cell/synaptic interaction Intracellular protein trafficking Cilia maintenance pH regulation Phagocytosis
What is a symptom of mutations to RPE65, what is this condition called, and what is its inheritance pattern? When is it typically diagnosed?
Blindness with autosomal recessive inheritance
Typically diagnosed within the first few years of life
Also known as leber congenital amaurosis
Mutations to how many genes can cause leber congenital amaurosis?
> 12 genes
What percentage of RPE65 mutations does leber congenital amaurosis account for?
6%
Name 5 means of subjectively assessing retinal function in retinitis pigmentosa.
Visual acuity Contrast sensitivity Flicker sensitivity Dark adaptation Visual fields
Name 2 means of objectively assessing retinal function in retinitis pigmentosa.
Pupil response
Electrophysiology
What is the EOG and what is it modified by?
The ocular resting potential
It is modified by derivatives of retinol acting on potassium channels in the RPE
Name 5 conditions that alter the EOG, and name what specifically they alter, define how its obtained, and the normal value.
Vitamin A deficiency RPE diseases Retinal toxicity Diabetes Retinal dystrophies They alter the arden ratio, which is the light peak / dark trough, normally >2.0
What does the arden ratio represent?
The maximal K+ buffering capacity of the RPE - RPE function.
During an ERG, what happens to the radial retinal and lateral currents?
Radial retinal currents sum up
Lateral currents cancel out
What does the a-wave of an ERG quantify?
Phototransduction
What does the b-wave of an ERG quantify?
ON bipolar cell responses
What does a visual evoked potential measure?
A response from the visual cortex in response to a visual stimulus (checkerboard pattern).
Name 4 applications of visual evoked potentials.
Amblyopia
Potential acuity albinism
Intectness of visual pathway (stroke/mass)
Animal axperiments
What occurs at the optic chiasm of albinos and what percentage?
What does this result in on a VEP?
An abnormal decussation at the chiasm, 55%.
L or R eye stimulation gives an abnormal lateralisation on a VEP signal.
How are VEP potential acuity estimates done (2)?
Record VEP amplitude to checks of varying size.
Extrapolate aplitude vs check size to baseline (0).
What does an ERG a-wave represent if dark/light adapted?
Light adapted - cone photoreceptor response
Dark adapted - rod photoreceptor response
What does an ERG b-wave represent if dark/light adapted?
Light adapted - cone bipolar response
Dark adapted - rod bipolar response
What does the c-wave of an ERG quantify?
RPE response
What does the d-wave of an ERG quantify?
OFF bipolar cell response
What do the oscillatory potentials of an ERG quantify?
Feedback between amacrine, bipolar, and ganglion cells
What does the STR of an ERG quantify?
Scotopic threshold response
Ganglion cell response
What do P50 and P75 on a VEP represent?
LGN generator
What does P100 on a VEP represent?
Visual cortex
What does >180ms on a VEP represent (2)?
Association areas
Conscious processing
Name a potential means of gene therapy for retinal degeneration, and the requirements for it.
Name the method, and how it works and what it involved.
If photoreceptors are still there, the deficient gene can be reinserted.
Done using adeno-associated virus (AAV).
It is a small virus that infects humans and primates.
It incorporates its genome into a host cell.
Name 4 reasons why adeno-associated virus is suitable for gene therapy use.
Not currently known to cause diseases
Causes a very mild immune response
Infects both dividing and non-dividing cells
Incorporates its genome into the host cell
