Hebrew University of Jerusalem researchers have found for the first time that a
specific protein is essential not only for maintaining a healthy retina but may
also have implications for other conditions involving the immune, reproductive,
vascular and nervous systems, as well as for cancers.
Their work,
reported recently in the journal Neuron, highlights the role of “Protein S” in
the maintenance of a healthy retina through its involvement in the process of
pruning photoreceptors, the light-sensitive neurons in the eye. This process is
also referred to as phagocytosis.
These photoreceptors keep growing and
elongating from their inner end. In order to maintain a constant length, they
must be pruned from their outer end by specialized cells called retinal pigment
epithelial cells. Without such pruning – which also clears away many free
radicals and toxic byproducts generated during visual biochemical reactions –
photoreceptors would succumb to toxicity and degenerate, leading if unchecked to
blindness.
A receptor molecule called Mer is a key in photoreceptor
pruning and is thus vital for retinal health.
Mutations in the mouse, rat
and human Mer genes cause retinal degeneration, which finally leads to
blindness.
The published HU study, headed by Dr. Tal Burstyn-Cohen of the
Institute of Dental Sciences and colleagues at the Salk Institute in California,
focuses on the molecules activating Mer in this pruning mechanism. Although two
such molecules – Gas6 and Protein S – were identified previously, it was yet to
be proven that they also play a role in a living organism. To show this, the
researchers found in their experiments on laboratory animals that both Gas6 and
Protein S are needed to activate pruning of retinal photoreceptors, and thus
maintain a healthy retina.
These findings could have practical
implications, they wrote, since Protein S also functions as a potent
anticoagulant.
People with Protein S deficiency are at risk for
life-threatening blood clots, and thromboembolism – a clot that breaks loose and
is carried by the blood stream to plug another vessel.
These results
further open new avenues of research into the role of Protein S in activating
the receptors in other tissues where its function has been shown to be
important, such as in the immune, reproductive, vascular and nervous systems, as
well as in various cancers where activation of receptors has been observed. For
example, since Protein S is important for blood vessel formation, neutralizing
Protein S in the blood vessels supplying blood to cancer growths could interfere
with the cancer’s blood supply.
This project was initiated during
Burstyn-Cohen’s postdoctoral training at the Salk Institute in California, and
continued as a collaborative work from her newly established lab at the HU
Institute of Dental Sciences.
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