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Interestingly, in both Nuc1 astrocytes and in wild type astrocytes following knockdown of <jats:italic>Cryba1<\/jats:italic>, vascular endothelial growth factor (VEGF) secretion is decreased. This has led us to explore signaling mediators that could be regulated by \u03b2A3\/A1-crystallin to modulate both GFAP and VEGF. Several studies have shown that the signal transducer and activator of transcription 3 (STAT3) is involved in the co-regulation of GFAP and VEGF. We show that STAT3 and \u03b2A3\/A1-crystallin may co-regulate each other in astrocytes. Such co-regulation would create a positive feedback circuit; i.e., in the cytosol of astrocytes, \u03b2A3\/A1-crystallin is necessary for the phosphorylation of STAT3, which then dimerizes and translocates to the nucleus to form DNA-binding complexes, activating transcription of <jats:italic>Cryba1<\/jats:italic>. This stoichiometric co-regulation of STAT3 and <jats:italic>Cryba1<\/jats:italic> could potentiate expression of GFAP and secretion of VEGF, both of which are essential for maintaining astrocyte and blood vessel homeostasis in the retina. Consistent with this idea, <jats:italic>Cryba1<\/jats:italic> knockout mice exhibit an abnormal astrocyte pattern and defective remodeling of retinal vessels.<\/jats:p>","DOI":"10.1038\/srep08755","type":"journal-article","created":{"date-parts":[[2015,3,4]],"date-time":"2015-03-04T10:12:57Z","timestamp":1425463977000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["\u03b2A3\/A1-crystallin is a critical mediator of STAT3 signaling in optic nerve astrocytes"],"prefix":"10.1038","volume":"5","author":[{"given":"Mallika","family":"Valapala","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malia","family":"Edwards","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stacey","family":"Hose","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianfei","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Wawrousek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerard A.","family":"Lutty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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