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E. E. Geisert, J. P. Templeton, N. E. Freeman-Anderson, C. W. Abner; Modulation of Crystallin Network by Lipin1 is Associated With Neuroprotection in the Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3702.
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© ARVO (1962-2015); The Authors (2016-present)
In our ongoing efforts to define the molecular networks modulating neuronal survival, we examine the effects of a candidate gene (Lpin1) previously identified to affect neuronal survival and to alter genetic networks activated by optic nerve crush (ONC).
Using ONC as a model of retinal injury we examined the effects of a naturally occurring mutation in Lpin1 on ganglion cell survival. We counted the number of neurons surviving 30 days after ONC in Lpin1 mutant mice (MT) and in control wild-type mice (WT). For this portion of the study we used 6 normal MT retinas along with 6 ONC MT retinas. These were compared to counts from 5 normal WT retinas and 6 ONC WT retinas. We also studied changes in gene expression using Illumina microarray systems, comparing the Lpin1 MT with WT controls. The 6 groups (3 independent biological samples in each) include normal retinas (MT and WT), retinas 2 days after ONC (MT and WT), and 5 days after ONC (MT and WT).
The mutation in Lpin1 provided significant neuroprotection with 49% of the RGCs surviving in the MT mice and only 38% surviving in the WT control animals. Our microarray analysis revealed that the crystallin network (Templeton et al., 2009 BMC Neuroscience 10:90-) was up-regulated in the MT mice and down-regulated in the WT controls. Genes within this crystallin network include but are not limited to: Cryaa, Cryab, Cryba1, Cryba2, Cryba4, Crybb1, Crybb2, Crybb3, Crygb, Crygc, Crygn, Crygs, Grifin, Lim2, and Mip.
These results support the hypothesis that the upregulation of the crystallin network is neuroprotective. Furthermore, it appears that we have identified an upstream modulator of the crystallin network, Lipin1.
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