Cyp1b1-deficient retinal astrocytes are more proliferative and migratory and are protected from oxidative stress and inflammation.

Astrocytes (ACs) are the most abundant cells in the central nervous system. Retinal ACs play an important role in maintaining the integrity of retinal neurovascular function, and their dysfunction contributes to the pathogenesis of various eye diseases including diabetic retinopathy. Cytochrome P450 1B1 (CYP1B1) expression in the neurovascular structures of the central nervous system including ACs has been reported. We previously showed that CYP1B1 expression is a key regulator of redox homeostasis in retinal vascular cells. Its deficiency in mice resulted in increased oxidative stress and attenuation of angiogenesis in vivo and proangiogenic activity of retinal vascular cells in vitro. Here, using retinal ACs prepared from wild-type () and -deficient () mice, we determined the impact of Cyp1b1 expression on retinal AC function. We showed that retinal ACs were more proliferative and migratory. These cells also produced increased amounts of fibronectin and its receptors, αβ- and αβ-integrin. These results were consistent with the increased adhesive properties of ACs and their lack of ability to form a network in Matrigel. This was reversed by reexpression of Cyp1b1 in ACs. Although no significant changes were observed in Akt/SRC/MAPK signaling pathways, production of inflammatory mediators bone morphogenetic protein-7 (BMP-7) and monocyte chemoattractant protein-1 (MCP-1) was decreased in ACs. ACs also showed increased levels of connexin 43 phosphorylation and cluster of differentiation 38 expression when challenged with HO. These results are consistent with increased proliferation and diminished oxidative stress in cells. Thus, Cyp1b1 expression in ACs plays an important role in retinal neurovascular homeostasis.