Vasoinhibins Stimulate the Activity of the Inducible Form of Nitric Oxide Synthase in Rat Retina

Abstract

Purpose: : Vasoinhibins, a family of N–terminal fragments of prolactin that inhibit vascular function, are expressed in the retina, where they suppress blood vessel growth and dilation (IOVS 46:2947, 2005). Nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) can act as an antiangiogenic agent. Here we investigate the effects of vasoinhibins on iNOS expression and NOS activity in the retina.

Methods: : Rat and human vasoinhibins were injected intravitreously, and 24 hours after injection retinas were evaluated for iNOS expression by RT–PCR, Western blot, and immunohistochemistry, and for NOS activity by the L–citrulline assay and NADPH–diaphorase staining.

Results: : Vasoinhibins produced a significant increase of iNOS mRNA and protein in the retina that correlated with a higher level of NOS activity. Inducible NOS protein and NOS activity were localized in cells within the inner plexiform and ganglion cell layers of the retina.

Conclusions: : Vasoinhibins induce iNOS expression and NO production by cells within the inner retina. This action may contribute to the inhibitory effects of vasoinhibins on vascular function or to other retinal actions of iNOS.

Keywords: retina • nitric oxide • neuropeptides