title: Silencing of galectin-1 inhibits retinal neovascularization and ameliorates retinal hypoxia in a murine model of oxygen-induced ischemic retinopathy.
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.
authors.affiliation: Eye Center, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, Hubei, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Yang
authors.affiliation: Eye Center, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, Hubei, China.
authors.forename: Wenxi
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Eye Center, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, Hubei, China.
authors.forename: Tao
authors.initials: T
authors.lastname: He
authors.affiliation: Eye Center, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, Hubei, China. Electronic address: yiqiaoxing1111@hotmail.com.
authors.forename: Yiqiao
authors.initials: Y
authors.lastname: Xing
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D004195:Disease Models, Animal; D037483:Galectin 1 / Q000096:biosynthesis / Q000235:genetics*; D020868:Gene Silencing; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D058449:Intravitreal Injections; D007511:Ischemia / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D009593:Nitroimidazoles / Q000008:administration & dosage; D010100:Oxygen / Q000633:toxicity; D012313:RNA / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D015861:Retinal Neovascularization / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D037483:Galectin 1; D009593:Nitroimidazoles; D012333:RNA, Messenger; C033815:pimonidazole; D012313:RNA; D010100:Oxygen
keywords: Galectin-1; Intravitreal injection; Oxygen-induced retinopathy; RNA interference; Retinal hypoxia; Retinal neovascularization; Retinopathy of prematurity