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

Publications // Sheibani Lab // Mar 21 2019

PubMed ID: 30892936

Author(s): Falero-Perez J, Sorenson CM, Sheibani N. Cyp1b1-deficient retinal astrocytes are more proliferative and migratory, and are protected from oxidative stress and inflammation. Am J Physiol Cell Physiol. 2019 Mar 20. doi: 10.1152/ajpcell.00021.2019. [Epub ahead of print]

Journal: American Journal Of Physiology. Cell Physiology, Mar 2019

Astrocytes (AC) are the most abundant cells in the central nervous system. Retinal AC 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 AC 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 AC prepared from wild type ( Cyp1b1+/+) and Cyp1b1-deficient ( Cyp1b1-/-) mice, we determined the impact of Cyp1b1 expression on retinal AC function. We showed that Cyp1b1-/- retinal AC were more proliferative and migratory. These cells also produced increased amounts of fibronectin and its receptors αvβ3 and α5β1 integrins. These results were consistent with the increased adhesive properties of Cyp1b1-/- AC, and their lack of ability to form a network in Matrigel. This was reversed by re-expression of Cyp1b1 in Cyp1b1-/- AC. Although no significant changes were observed in AKT/SRC/MAPK signaling pathways, the production of inflammatory mediators BMP7 and MCP1 were decreased in Cyp1b1-/- AC. Cyp1b1-/- AC also showed increased levels of connexin 43 phosphorylation, and CD38 expression when challenged with H2O2. These results are consistent with increased proliferation and diminished oxidative stress in Cyp1b1-/- cells. Thus, Cyp1b1 expression in AC plays an important role in retinal neurovascular homeostasis.