Lecture 12: Age-related Macular Degeneration Flashcards

1
Q

What is AMD

A

a medical condition which may result in blurred or no vision in the centre visual field

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2
Q

AMD:

A

Age-related Macular Degeneration

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3
Q

simple test for AMD and what are the effect of AMD on vision

A

-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
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4
Q

two forms of AMD:

A

wet and dry

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5
Q

Wet form characterised by

A

the growth of ned blood vessels within diseased retinal tissue and subsequent haemorrhaging from them
-“drusen”

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6
Q

dry form different to wet as

A
  • little or no haemorrhaging in dry form

- early predictive signs of both inclue “drusen” - fatty deposits on the retina

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7
Q

anatomy of the eye: front of eye to back

A
  • cornea
  • iris
  • pupil
  • lens
  • macula –> Fovea
  • blood vessels
  • retina
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8
Q

cross section of the Macula & its role in the eye

A
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)
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9
Q

what are drusen

A

Extracellular material that builds up between Bruch’s membrane and the retinal pigment epithelium of the eye

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10
Q

what happens during progression of AMD

A
  • 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
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11
Q

What function do RPE cells perform?

A

(1) Regeneration of bleached opsins.
(2) Phagocytosis
(3) Transepithelial transport.
(4) Secretion of growth factors
(5) absorption of light
(6) protection against photo- oxidation

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12
Q

AMD is the underlying disease process in…

A

..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

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13
Q

can cell transplantation cure AMD?

A

YES

-Autologous RPE transplant maintains/restores sight in humans affected by AMD

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14
Q

how does cell transplantation work for AMD?

A
  • Neural retina resected to reveal RPE layer

- section placed in fovea to replace damaged cells

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15
Q

If autologous transplantation works, then whats the problem?

A
  • 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)
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16
Q

can cultured cells RPE cells grown from post mortem material be used?

A

PROBABLY;

•In vitro produced human RPE maintains sight when transplanted in RCS rat (experiment rodent head tracking)

17
Q

if cultured adult RPE cells work, whats the problem?

A
  • 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
18
Q

what other routes exist to generate RPE cells in vitro?

A
  • human embryonic stem cells?

- patient specific iPS cells?

19
Q

transplanted RPE preserve _____ in RCS rats

A

photoreceptors

20
Q

how do you deliver RPE cells

A

-patients are typically elderly, with aged Bruchs membrane.
-cell suspensions may fail to attach to Bruchs membrane
SOLUTION: manufacture an artificial membrane

21
Q

patch assembly (RPE integration)

A

RPE cells in suspension at high density + Bare patch –> RPE cell coated patch

22
Q

describe amount of RPE cells from human embryonic stem cells

A

potentially inexhaustible

23
Q

prototype novel therapeutic vehicle (cell coated patch) was ineffective/effective in preliminary tests

A

EFFECTIVE

-clinical trials now underway to test safety and soon efficacy