Emerging Therapies: Retinal & Macular Degenerations

PHAR 40040 (2013)

Dr. Breandn Kennedy
UCD Conway Institute

Refs:
"The Eye, Basic Sciences in Practice"
2nd Ed (Forrester, Dick, McMenamin, Lee, Saunders)

http://webvision.med.utah.edu/photo1.html

L1: Overview of Course Goals
L2: Vision
Learning objectives:

1. Understand the hallmarks of retinal and macular degenerations

2. Understand the general therapeutic approaches to RD/MD (cell-,
drug- & gene-based)

3. Understand the logic behind use of these therapeutic approaches
for RD/MD and specific advantages/disadvantages of the eye

4. Display ability to critically evaluate the scientific/clinical evidence
on the effectiveness/potential of these approaches.


I. The Human Eye
Eye enables vision
i.e. capture of image of external surroundings
Environmental light

Detected by photoreceptors in retina

Signal to brain via optic nerve

Vision
Human Eye
-sphere ~2.5 cm in diameter
-vol. of ~6.5 mls
-detects light of 400-700 nm
wavelengths
-the window to the brain
-an approachable part of the
brain
Important Eye Disease that Can Result in Blindness

-Glaucoma

-Retinal / Macular Degenerations

-Uveitis

-Colour Blindness
-Anophthalmia/Microphthalmia

-genetic vs non-genetic
In US, blindness costs the government ~$4 billion annually
Structural Arrangement of RETINAL Cells
http://webvision.med.utah.edu/sretina.html
Two or three types of
cone photoreceptor and
a single type of rod
photoreceptor are
present in the normal
mammalian retina.

Some non-mammalian
retinas have even more
cone types
Rod & Cone
Photoreceptors
Structure of a rod photoreceptor
phototransduction
Cones are clustered in the
specialised foveal region of
the retina
Molecular basis of how we see; photopigments
PHOTOTRANSDUCTION

-photopigment comprises 11-cis-retinal plus an opsin protein

-retina detects different wavelengths of light as different 11-cis-retinal:opsin
combos have different Abs. Max.
e.g. rod pigments = 11-cis-retinal + rhodopsin
blue pigments = 11-cis-retinal + blue cone opsin
Colour Vision
ANALYSIS OF BLINDNESS
Functional
ERG
Pupil Dilation
Behaviour/Obstacle Course
Morphological
Histology
Fundoscopy
OCT

Vision -------Retinal/Macular Degeneration -----Blindness
Goal: prevent or reverse blindness due to retinal degeneration
Emerging Approaches:
-1) Pharmacological
-2) Gene-Based
-3) Cell-Based
ADDITIONAL RESOURCES
http://www.youtube.com/watch?v=VrEXkiTcyiU
http://www.youtube.com/watch?v=Fm45A4yjmvo
http://webvision.med.utah.edu/book/electrophysiology/the-
electroretinogram-clinical-applications/