Abstract
Purpose: :
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).
Methods: :
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).
Results: :
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.
Conclusions: :
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.
Keywords: protective mechanisms • gene modifiers • gene microarray