RhoB antibody alters retinal vascularization in models of murine retinopathy.

Autor: Almonte-Baldonado R; Lilly Research Laboratories, New York, New York., Bravo-Nuevo A; Lankenau Institute for Medical Research, Wynnewood, Pennsylvania., Gerald D; Lilly Research Laboratories, New York, New York., Benjamin LE; Lilly Research Laboratories, New York, New York., Prendergast GC; Lankenau Institute for Medical Research, Wynnewood, Pennsylvania., Laury-Kleintop LD; Lankenau Institute for Medical Research, Wynnewood, Pennsylvania.
Jazyk: angličtina
Zdroj: Journal of cellular biochemistry [J Cell Biochem] 2019 Jun; Vol. 120 (6), pp. 9381-9391. Date of Electronic Publication: 2018 Dec 09.
DOI: 10.1002/jcb.28213
Abstrakt: Neovascularization in cancer or retinopathy is driven by pathological changes that foster abnormal sprouting of endothelial cells. Mouse genetic studies indicate that the stress-induced small GTPase RhoB is dispensable for normal physiology but required for pathogenic angiogenesis. In diabetic retinopathy, retinopathy of prematurity (ROP) or age-related wet macular degeneration (AMD), progressive pathologic anatomic changes and ischemia foster neovascularization are characterized by abnormal sprouting of endothelial cells. This process is driven by the angiogenic growth factor VEGF, which induces and supports the formation of new blood vessels. While injectable biologics targeting VEGF have been used to treat these pathological conditions, many patients respond poorly, prompting interest in other types of mechanism-based therapy. Here we report the preclinical efficacy of a monoclonal antibody that specifically targets RhoB, a signaling molecule that is genetically dispensable for normal physiology but required for pathogenic retinal angiogenesis. In murine models of proliferative retinal angiogenesis or oxygen-induced retinopathy, administering a monoclonal RhoB antibody (7F7) was sufficient to block neoangiogenesis or avascular pathology, respectively. Our findings offer preclinical proof of concept for antibody targeting of RhoB to limit diabetic retinopathy, ROP or wet AMD and perhaps other diseases of neovasculogenesis such as hemangioma or hemangiosarcoma nonresponsive to existing therapies.
(© 2018 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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