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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