Small
vessel diseases, such as ischemic retinopathy and cerebral small vessel
disease (CSVD), are increasingly recognized in patients with diabetes,
dementia and cerebrovascular disease. The mechanisms of small vessel
diseases are poorly understood, but the latest studies suggest a role
for semaphorins. Initially identified as axon guidance cues, semaphorins
are mainly studied in neuronal morphogenesis, neural circuit assembly,
and synapse assembly and refinement. In recent years, semaphorins have
been found to play important roles in regulating vascular growth and
development and in many pathophysiological processes, including
atherosclerosis, angiogenesis after stroke and retinopathy. Growing
evidence indicates that semaphorins affect the occurrence, perfusion and
regression of both the macrovasculature and microvasculature by
regulating the proliferation, apoptosis, migration, barrier function and
inflammatory response of endothelial cells, vascular smooth muscle
cells (VSMCs) and pericytes. In this review, we concentrate on the
regulatory effects of semaphorins on the cell components of the vessel
wall and their potential roles in microvascular diseases, especially in
the retina and cerebral small vessel. Finally, we discuss potential
molecular approaches in targeting semaphorins as therapies for
microvascular disorders in the eye and brain.
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