Truncated netrin-1 contributes to pathological vascular permeability in diabetic retinopathy

Melanocortin receptor agonists MCR1‐5 protect photoreceptors from high‐glucose damage and restore antioxidant enzymes in primary retinal cell culture

“…Moreover, it has been shown that a-MSH or other MCR agonists has immunosuppressive activity in experimental uveitis [25,31] and also protects retinal endothelial cells from oxidative-induced damage [32]. Fitting with this knowledge, in an initial study, we described for the first time that MCR 1,5 agonists help diabetic retinopathy by concretely protecting retinal vascular network [13,32] in a murine model, through the inhibition of the local inflammatory and immune responses [13]. To these pioneering results have been added now the new data of an antioxidant and defensive response of the retinal cells following activation of MCR 1,5 .…”

“…Hyperglycaemia is one of the most common complications of diabetes leading to vision impairment worldwide [1,2]. Hyperglycaemia is also accompanied by oxidative misbalance.…”

“…Melanocortin receptors (MCR) represent a family of G-proteincoupled receptors classified in five subtypes (MCR [1][2][3][4][5] ) [13][14][15]. MCR are expressed in several tissues including retina [9,16], and they can be activated or inhibited by either agonists as a-melanocyte-stimulating hormone (a-MSH) or antagonists as agouti-related protein [17].…”

Comprehensive analysis of mouse retinal mononuclear phagocytes

“…In fact, most recent in situ analyses of ramified and reactive retinal microglia rely on Iba1 staining [26][27][28][29][30] as the marker allows consistent and reliable staining of microglia somata and their processes in a broad spectrum of different activation phenotypes [31][32][33] . In general, a combined in situ analysis of retinal microglia using sections and flat mounts as presented in our protocol is recommended.…”

Placental labyrinth formation in mice requires endothelial FLRT2–UNC5B signaling

“…Netrin 1 has long been thought to be the functional ligand of UNC5B, with absence of netrin 1/UNC5B signaling being responsible for the vascular defects in UNC5B-deficient mice (Lu et al, 2004;Larrivée et al, 2007). Indeed, proteolytic fragments of netrin 1 bind UNC5B in diabetic endothelial cells and increase vascular permeability (Miloudi et al, 2016). However, in terms of developmental angiogenesis, the situation regarding the role of netrin 1/UNC5B signaling is complex and has been subject to debate; notably, the abnormalities reported for UNC5B-deficient mice are absent in netrin 1 mutants (Serafini et al, 1996;Wilson et al, 2006;Castets and Mehlen, 2010;Yung et al, 2015).…”