Zhang Y. Porat R M. Alon T. Keshet E. Stone J [a].
Tissue oxygen levels control astrocyte movement and differentiation in developing retina, Brain Research. Developmental Brain Research 118(1-2) :135-145, 1999.
Abstract
Astrocytes play a key role in the development of retinal
vessels by detecting hypoxia in developing retina and secreting the
hypoxia-induced angiogenic factor VEGF to induce vessel formation. The
astrocytes which play this role are themselves spreading
over the retina, just ahead of the growing vessels. To understand the
mechanisms which keep astrocytes in this strategic 'just
ahead' position we have studied the effects of hyperoxia and hypoxia on
astrocyte differentiation and movement in
situ in neonatal rat retina and in primary culture. Hyperoxia in situ
inhibited the stellation of astrocytes, so that they
persisted in a relatively unbranched form, which accumulated at the edge of
their spreading population; hyperoxia permitted but did not accelerate
migration. Conversely, hypoxia induced unstellated
astrocytes to stellate within 6 h. If the hypoxia was
abnormally severe, it caused the astrocytes to hyperstellate
and slowed their spread. Astrocytes in primary culture did
not change morphology or motility when challenged by hypoxia. When treated
with medium conditioned by retina however, astrocytes became
mobile and, if the medium was conditioned by hypoxic retina, became stellate.
These results suggest that the oxygen released by retinal vessels maintains
the mobility of astrocytes, via a diffusible factor released
by other retinal cells. Conversely, naturally generated hypoxia of developing
retina plays a triple role, inducing astrocytes to stellate,
to end their migration and to produce VEGF, thereby inducing vessel
formation. The induction of stellation is mediated by a diffusible factor
released by other retinal cells. Thus hypoxia of the retina generated by
neural maturation induces key events in both the differentiation of
astrocytes and the formation of blood vessels.
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