Abstract
Abstract: :
Purpose: Clinical studies suggest that premature infants given a dietary supplement of inositol have decreased incidence and severity of retinopathy of prematurity (ROP). In order to investigate inositol’s role in the inhibition of neovascularization (NV), inositol was tested as an inhibitor of vascular endothelial growth factor (VEGF)–induced proliferation and differentiation, and in an in vivo model of ROP. Methods: In vitro, the effect of inositol on VEGF– induced retinal endothelial cell proliferation and differentiation was tested in bovine retinal microvascular endothelial cells (BRMEC). The concentration of inositol ranged from 100mM to 0.01µM. Proliferation was quantified by an MTT assay. Differentiation was quantified by a tube formation assay. In vivo, inositol was tested in a well–established rat model of ROP by intravitreal injection of 5 µL doses of concentrations ranging from 10 mM to 0.01mM. Results: Inositol showed no effect upon VEGF–induced BRMEC proliferation below 100mM. However, inositol inhibited VEGF–induced tube formation of BRMEC in the range of doses from 100 µM to 0.1µM. Inositol treatment reduced pathological retinal NV in a dose dependent manner. The groups receiving 1mM and 10mM injections showed 50% inhibition of NV relative to vehicle. Normal vasculogenesis, assessed by vascular area, was unaffected. Conclusions: Inositol effectively inhibits BRMEC tube formation, but not proliferation. When the retina is directly treated with inositol, NV is significantly reduced. Because it is a ubiquitous and endogenous molecule, inositol treatment can be a non–invasive and effective inhibitor of ROP.
Keywords: retinopathy of prematurity • retinal neovascularization • vascular cells