LAUSR

Abstract Aberrant neovascularization is a consequence of inappropriate angiogenic signaling and contributes to several diseases. Although many regulators of pathogenic angiogenesis have been identified, the understanding of this process remains incomplete. Galectin‐1 (Gal‐1), as a homodimeric protein with a single carbohydrate‐recognition domain, is implicated in several pathologic processes, including angiogenesis; however, its involvement in retinal neovascularization (RNV) remains unknown. Here, we investigated the anti‐angiogenic effect of silencing Gal‐1 through intravitreal injection in a mouse model of oxygen‐induced retinopathy (OIR). Our results revealed that Gal‐1 was overexpressed and closely related to retinal neo‐vessels in OIR retinas. After silencing Gal‐1 via intravitreal injection of adenoviral‐Gal‐1‐RNA interference (Ad‐Gal‐1‐RNAi), RNV and retinal hypoxia were significantly attenuated, indicating the anti‐angiogenic effect of Gal‐1 inhibition. Western blot analysis and real‐time polymerase chain reaction indicated that the expression of both neuropilin‐1 (Nrp‐1) and B cell lymphoma‐2 (Bcl‐2) decreased after intravitreal injection of Ad‐Gal‐1‐RNAi, implying the possible involvement of Nrp‐1 and Bcl‐2 in Gal‐1‐related angiogenic processes. Additionally, whole‐mount fluorescence and hematoxylin and eosin staining showed that intravitreal injection of Ad‐Gal‐1‐RNAi did not significantly disrupt the retinal vasculature and neuronal structure of room air mice. Moreover, Ad‐Gal‐1‐RNAi transfer promoted retinal vascular sprouting and increased retinal vascular perfusion, likely through decreased phosphorylation of myosin phosphatase target protein‐1. Collectively, our results demonstrated that Gal‐1 functions as an important regulator in RNV and offers a promising strategy for the treatment of RNV diseases, such as proliferative diabetic retinopathy and retinopathy of prematurity. HighlightsGalectin‐1(Gal‐1) is overexpressed in OIR model.Silencing of Gal‐1 reduced RNV and alleviated retinal hypoxia in OIR.Silencing of Gal‐1 may promotes vascular normalization through inhibition of ROCK activation in OIR.