Inhibition of neuroretinal cell death by insulin-like growthfactor-1 and its analogs

[摘要] Purpose: Visual loss secondary to retinal ischemia/hypoxia can be aserious complication of diabetic retinopathy, as well as other vascularinsults. We used R28 retinal precursor cells, as well as primary ratretinal cell cultures, to test whether the neuroprotective growth factorIGF-1 would protect retinal cells from dying under conditions of hypoxiaor serum-starvation. We also utilized three IGF-1 analogs ([LongR3],[Ala31], and [Leu24][Ala31]) with altered affinities for the IGF-1receptor and/or IGF-1 binding proteins in order to address themechanism(s) of IGF-1 neuroprotection.Methods: Retinal cultures were subjected to hypoxia (95% N2/5%CO2 for 0-8 h), or serum-starvation (0% serum for 48 h).Experimental cultures were pre-treated for 24 h with 0-100 ng/ml ofIGF-1 or its analogs. Retinal cultures were analyzed for the extent ofcell death by trypan blue exclusion assay, TUNEL in situ, as well asssDNA analysis specific for apoptosis.Results: IGF-1 and all three IGF-1 analogs tested were able toinhibit neuroretinal cell death at a concentration of 50 ng/ml.Neuroprotection was evident under conditions of hypoxia orserum-starvation.Conclusions: IGF-1, as well as IGF-1 analogs, improves survival ofneuroretinal cells in vitro, under conditions of hypoxia orserum-starvation. Since all three IGF-1 analogs inhibit cell death tosome degree, we interpret these results to mean that IGF-1-mediatedinhibition of cell death does not depend upon strong affinities for theIGF-1 receptor or IGF-1 binding proteins. Further studies will revealadditional information as to the pathways responsible for IGF-1-mediatedneuroprotection of retinal cells.

[学科分类] 生物化学/生物物理