Intravitreally injected anti-VEGF antibody reduces brown fat in neonatal mice

Jo, D.H., Park, S.W., Cho, C.S., Powner, M. B., Kim, J.H., Fruttiger, M. & Kim, J.H. (2015). Intravitreally injected anti-VEGF antibody reduces brown fat in neonatal mice. PLoS ONE, 10(7), doi: 10.1371/journal.pone.0134308

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Abstract

Anti-vascular endothelial growth factor (VEGF) agents are the mainstay treatment for various angiogenesis-related retinal diseases. Currently, bevacizumab, a recombinant humanized anti-VEGF antibody, is trailed in retinopathy of prematurity, a vasoproliferative retinal disorder in premature infants. However, the risks of systemic complications after intravitreal injection of anti-VEGF antibody in infants are not well understood. In this study, we show that intravitreally injected anti-VEGF antibody is transported into the systemic circulation into the periphery where it reduces brown fat in neonatal C57BL/6 mice. A considerable amount of anti-VEGF antibody was detected in serum after intravitreal injection. Furthermore, in interscapular brown adipose tissue, we found lipid droplet accumulation, decreased VEGF levels, loss of vascular network, and decreased expression of mitochondriarelated genes, Ppargc1a and Ucp1, all of which are characteristics of "whitening" of brown fat. With increasing age and body weight, brown fat restored its morphology and vascularity. Our results show that there is a transient, but significant impact of intravitreally administered anti-VEGF antibody on brown adipose tissue in neonatal mice. We suggest that more attention should be focused on the metabolic and developmental significance of brown adipose tissue in bevacizumab treated retinopathy of prematurity infants. Copyright:

Item Type: Article
Subjects: R Medicine > RE Ophthalmology
Divisions: School of Health Sciences > Department of Optometry & Visual Science
URI: http://openaccess.city.ac.uk/id/eprint/14169

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