Purchase this article with an account.
LI PAN, Xin Wei, Kin-Sang Cho, Chi-wai Do, Dong Feng Chen; A Role for Insulin-like Growth Factor Binding Protein-like 1 in Microglia. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4008.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
We recently showed that insulin-like growth factor binding protein-like 1 (IGFBPL1) plays a vital role in promoting axon growth and survival of retinal ganglion cell (RGC) during retina development. Such effect requires the presence of insulin-like growth factor 1 (IGF-1) and is mediated through IGF-1 receptor (IGF-1R). Since adult RGCs are known to express a low or undetectable level of IGF-1R, we aimed to study whether IGFBPL1 directly supports RGC survival after injury in the retina.
Expressions of IGF-1, IGFBPL1 and IGF-1R in the adult retina were examined in retinal whole-mounts using immunohistochemistry. The retinal whole-mounts were double-immunolabeled with primary antibody against an RGC marker Brn-3a, or microglial marker Iba-1 to identify cell type-specific expression of IGF-1, IGF-1R and IGFBPL1.Co-cultures of purified microglia and RGCs isolated from postnatal day 5 Cx3CR1/GFP mice were performed, either in the presence or absence of 1μg/ml lipopolysaccharide (LPS) and/or 400ng/ml IGFBPL1 and 400ng/ml IGF-1. Neuronal survival was determined by Live/Dead Viability kit, and the percentage of surviving RGCs was quantified using Image J software.
Our result showed that IGF-1, IGF-1R, and IGFBPL1 were expressed by microglia, but not RGCs, in adult mouse retina. Addition of IGF-1 and/or IGFBPL1 to purified RGC cultures did not promote neuron survival. LPS stimulated microglia activation and caused significant RGC death compared to the control cultures (P<0.05). IGF-1 and/or IGFBPL1 significantly attenuated the neuronal cell death in LPS-treated microglia-induced RGC death in microglia-RGC co-cultures.
The present study reveals that IGFBPL1 is expressed by microglia rather than RGCs in adult mice. It exerts a neuroprotective effect by acting on microglia. Our result suggests that IGFBPL1 may protect neuronal death through modulating neuroinflammation.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
This PDF is available to Subscribers Only