Lecture 12: Age-related Macular Degeneration Flashcards
What is AMD
a medical condition which may result in blurred or no vision in the centre visual field
AMD:
Age-related Macular Degeneration
simple test for AMD and what are the effect of AMD on vision
-test: Amsler chart: showed skewed and cant see spot in middle.
- alow recovery of visual function after exposure to bright light (photostress test)
- visual acuity drastically decreasing
- blurred vision
- trouble discerning colours
- a loos in contrast sensitivity
two forms of AMD:
wet and dry
Wet form characterised by
the growth of ned blood vessels within diseased retinal tissue and subsequent haemorrhaging from them
-“drusen”
dry form different to wet as
- little or no haemorrhaging in dry form
- early predictive signs of both inclue “drusen” - fatty deposits on the retina
anatomy of the eye: front of eye to back
- cornea
- iris
- pupil
- lens
- macula –> Fovea
- blood vessels
- retina
cross section of the Macula & its role in the eye
back to front -the choroid -Bruch's membrane -retinal pigment epithelium -cone cells light enters here waste products go back (towards choroid) nourishment forward (cone cells)
what are drusen
Extracellular material that builds up between Bruch’s membrane and the retinal pigment epithelium of the eye
what happens during progression of AMD
- Retinal pigment epithelium (RPE) cells toward the rear of the retina malfunction and die- a key defining feature of the disease
- Photoreceptors (rods and cones) adjacent to the RPE cells die
- Choroid layer containing blood vessels develops abnormal structure and physically displaces overlying neural retina
What function do RPE cells perform?
(1) Regeneration of bleached opsins.
(2) Phagocytosis
(3) Transepithelial transport.
(4) Secretion of growth factors
(5) absorption of light
(6) protection against photo- oxidation
AMD is the underlying disease process in…
..over half of people registered blind or partially sighted in the UK
•Dry variant accounts for 90% of cases and is currently incurable
•Total cost of blindness may be as high as £8.8bn per annum in the UK alone
can cell transplantation cure AMD?
YES
-Autologous RPE transplant maintains/restores sight in humans affected by AMD
how does cell transplantation work for AMD?
- Neural retina resected to reveal RPE layer
- section placed in fovea to replace damaged cells
If autologous transplantation works, then whats the problem?
- Restoration of central vision is at the expense of an area of peripheral vision
- Lengthy and technically challenging operation to
- i) remove intact RPE layer from retina and •ii) successfully implant RPE at disease site
- Follow up surgical procedure required to remove compression medium (oil drop)
can cultured cells RPE cells grown from post mortem material be used?
PROBABLY;
•In vitro produced human RPE maintains sight when transplanted in RCS rat (experiment rodent head tracking)
if cultured adult RPE cells work, whats the problem?
- Donor material is hard to com bey
- RPE cells show a limited capacity to proliferate IN VITRO
- RPE phenotype tends to degenerate with time in culture
- some robust cell lines have been established, but these are mostly karyotypically abnormal and their similarity to normal RPA is questionable
what other routes exist to generate RPE cells in vitro?
- human embryonic stem cells?
- patient specific iPS cells?
transplanted RPE preserve _____ in RCS rats
photoreceptors
how do you deliver RPE cells
-patients are typically elderly, with aged Bruchs membrane.
-cell suspensions may fail to attach to Bruchs membrane
SOLUTION: manufacture an artificial membrane
patch assembly (RPE integration)
RPE cells in suspension at high density + Bare patch –> RPE cell coated patch
describe amount of RPE cells from human embryonic stem cells
potentially inexhaustible
prototype novel therapeutic vehicle (cell coated patch) was ineffective/effective in preliminary tests
EFFECTIVE
-clinical trials now underway to test safety and soon efficacy
