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Bone morphogenetic proteins regulate ionotropic glutamate receptors in human retina


Dr D. Higgins, as above.


Bone morphogenetic proteins (BMPs) are required for the development of retina, but their role in the mature eye is unknown. We therefore examined the expression of BMP-7 in adult human retina and assessed its effects on horizontal cells cultured from adult human retina. BMP-7 expression was detected in all retinal layers, with high levels of expression being present in the inner and outer nuclear layers. Human horizontal cells, found in the inner nuclear layer, possess both AMPA and kainate receptors, and glutamatergic agonists that activate these receptors induce prominent inward currents. Exposure to BMP-7 suppresses the kainate receptor current but enhances the AMPA receptor current. BMP-6, activin, and cartilage-derived morphogenic protein-2 (CDMP-2) have similar effects to BMP-7 and act just as rapidly (< 1 s). In contrast BMP-2 and transforming growth factor-β2 are inactive. The actions of BMP-7 on both AMPA and kainate receptors were blocked by the nonselective kinase inhibitor, staurosporine. In contrast, the serine/threonine kinase inhibitors blocked only the effects of BMP-7 on the AMPA current. Thus, BMPs rapidly and differentially regulate two ionotropic glutamate receptors through distinct pathways, neither of which involves nuclear regulatory activity. These observations suggest that BMPs might modify synaptic function in the mature nervous system.