Making new blood vessels: keeping the lines of sight open
By Journal of Clinical Investigation
Jan 20, 2006, 13:56

The creation of new blood vessels, known as angiogenesis, is a process used to supply oxygen and nutrients at sites of tissue injury. Angiogenesis is known to be stimulated during hypoxia (low oxygen conditions, when new vessels are needed). However, the mechanisms by which hypoxia leads to new vessel formation is poorly understood.

In the mouse retina specialized cells called astrocytes regulate angiogenesis by producing a structural support protein known as fibronectin during hypoxia, but until now it was unclear what triggered this pro-angiogenic event. In a new study appearing online on January 19 in advance of print publication in the February 2006 issue of the Journal of Clinical Investigation, Akiyoshi Uemura and colleagues from the RIKEN Center for Developmental Biology in Japan show that a nuclear protein called Tlx in pro-angiogenic astrocytes is regulated by oxygen levels.

Mice that were genetically engineered so that they would not express Tlx (known as "Tlx knockout" mice) show a complete absence of retinal blood vessels even though other pro-angiogenic markers are expressed. To determine whether the astrocytes were altered, the authors analyzed fibronectin levels in normal and Tlx knockout mouse retinas. The Tlx knockout astrocytes did not form fibronectin matrices, thus explaining the failure of these mice to undergo retinal angiogenesis. The authors also discovered that Tlx is induced by low oxygen levels and that Tlx gene levels are downregulated during hyperoxia (too much oxygen), revealing that Tlx is an oxygen-sensing switch in retinal astrocytes.

Together these studies demonstrate that oxygen-sensing Tlx plays an indispensable role in the development of healthy vascularized retinas via the regulation of formation of the fibronectin scaffold by pro-angiogenic astrocytes.

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