A short presentation on cGMP mediated Photo-transduction in Rod cells

1. PURNIMA KARTHA. N

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Second messengers are molecules that relay signals received at
receptors on the cell surface — such as the arrival of protein
hormones, growth factors, etc. — to target molecules in the
cytosol and/or nucleus.
Cyclic AMP, Cyclic GMP, Inositol
Triphosphate, Diacylglycerol, Calcium
ions, Nitric Oxide.

3. Earl W. Sutherland, Jr.
The Nobel Prize in Physiology or Medicine 1971 was awarded to Earl W.
Sutherland, Jr. "for his discoveries concerning the mechanisms of the action of
hormones".

4. • cGMP is synthesised from GTP by two isoforms of guanylyl cyclase, one which functions
when nitric oxide (soluble GC) is present and the other which acts as a receptor for
natriuretic peptides (membrane bound GC).
• cGMP exerts its actions through cGMP-gated cation channels, cGMP-dependent protein
kinases (PKGs), and cGMP-regulated phosphodiesterases (PDEs).
• cGMP is a common regulator of ion channel conductance, glycogenolysis, and cellular
apoptosis. It also relaxes smooth muscle tissues. In blood vessels, relaxation of vascular
smooth muscles lead to vasodilation and increased blood flow. cGMP is also a secondary
messenger in phototransduction in the eye.
cGMP

5. cGMP mediated Photo-transduction
in Rod cells
Direct support for the role of cGMP in rod-cell activity has been obtained in patch-
clamping studies using isolated patches of rod outer-segment plasma membrane, which
contains abundant cGMP-gated cation channels.
When cGMP is added to the cytosolic surface of these patches, there is a rapid increase in
the number of open ion channels.
cGMP acts directly on the ion channels to keep them open.
Three or four cGMP molecules must bind per channel in order to open it; this allosteric
interaction makes channel opening very sensitive to small changes in cGMP levels.

6. Human eye contains 2
types of photoreceptors:
Rods and Cones.
Rods contain a G- protein
coupled receptor called
Rhodopsin, made of
opsin and 11-cis retinal

7. Rhodopsin is activated as a result
of the absorption of light by the
associated small molecule 11-cis-
retinal, which then isomerizes to
all-trans-retinal, inducing a
conformational change in the
rhodopsin protein.

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Retinal diseases due to
mutations in RetGC1 and
PDE6
• Leber Congenital Amaurosis (LCA)
A form of congenital or early-infantile blindness due to mutations in retinal GC
leading to lack of cGMP.
• Cone- red dystrophy 6 (CORD6)
Cone rod dystrophy is evidenced by deterioration of photoreceptor cone and
rod cells and is caused due to the elevated levels of cGMP due to mutations in
GC.
• Retinitis pigmentosa
Retinitis pigmentosa (RP) is a group of genetic disorders that affect the retina’s
ability to respond to light. This inherited disease causes a slow loss of vision,
beginning with decreased night vision and loss of peripheral (side) vision. It is
due to mutations in cGMP phosphodiesterase enzymes in the retinal cells.

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