gene therapy for eye disease Flashcards
rpe functions
Absorption of light / heat, barrier function, transport of nutrients/ions/water, phagocytosis of shed OS, photopigment recycling (all-trans retinal -> 11-cis retinal)
monogenic conditions
Pathological variant in 1 gene
Different gene could be responsible for same condition (in diff people)
complex conditions
variants in more than one AND environmental factors
autosomal recessive inheritance
Two copies of fault required (one from each parent)
Disease = loss of function (no / little useable protein)
EXAMPLE: ABCA4 IRD
Transmembrane protein important for retinoid recycling (prevents vit a build up)
Can cause: macular dystrophy, RP (rod-cone dystrophy) , cone-rod dystrophy
x linked
Two copies of fault required (one from each parent)
Disease = loss of function (no / little useable protein)
EXAMPLE: ABCA4 IRD
Transmembrane protein important for retinoid recycling (prevents vit a build up)
Can cause: macular dystrophy, RP (rod-cone dystrophy) , cone-rod dystrophy
autosomal dominant
Trait is seen with one copy of variant
50% chance of passing on
Mechanisms of disease: loss of function, dominant negative and gain of function (2 alleles, 1 works, one doesn’t = negative affect)
EXAMPLE: Rho-related RP
RHO encodes rhodopsin
mitochondrial inheritance
maternal inheritance
loss of function gene therapy
Gene replacement or augmentation
Introduce healthy copy to restore function
ex vivo vs in vivo gene therapy
ex: gen modify out of body then back in
in: inject into cells
gain of function gene therapy
Gene silencing to disable exp of mutant gene
genome editing gene therapy
correcting altered genetic sequence directly
intravitreal administration
Deliver to vitreous cavity (injection)
Less invasive, but can dilute or cause extraocular shedding, maybe immune reaction
Risks: inflammation
subretinal gene therapy
Removal of vitreous jelly & excision of retina
Delivery where it needs to act (at level of Phr)
Risks: surgery risks
