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Eldon E Geisert, Felix L Struebing, Rebecca King, Louis R Pasquale, Allison E Ashley-Koch, Michael A Hauser, R Rand Allingham, Janey L Wiggs; GENOMIC LOCI MODULATING GANGLION CELL DEATH FOLLOWING ELEVATED IOP IN THE MOUSE. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3665.
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© ARVO (1962-2015); The Authors (2016-present)
The present study defines genomic loci modulating the susceptibility of retinal ganglion cells (RGC) to elevated intraocular pressure (IOP) in the BXD RI (recombinant inbred) mouse strain.
IOP was elevated by injecting magnetic microspheres into the anterior chamber and blocking the trabecular meshwork using a handheld magnet to impede drainage (Samsel et al, IOVS 2011; 52:1671-1675). The IOP was then measured over the next 21 days. Only animals with IOP greater than 25 mmHg for two consecutive days or an IOP above 30 mmHg on a single day after microsphere-injection were included in this study. On day 21, mice were sacrificed and the optic nerve was processed for microscopy. Axons were counted for both the injected and the control eye. A total of 38 BXD strains (130 mice) were included in the analysis. The percentage axon loss for each strain was calculated and the data was entered into genenetwork.org.
Using the Quantitative Trait Locus (QTL) mapping tool, we identified one major significant QTL (LRS of 41) on Chromosome 18 between 78 and 87 Mb. This QTL on Chromosome 18 has significant (p < 0.01) interactions with loci on additional other chromosomes. We are currently analyzing the pair-wise interactions between genes on different chromosomes to identify interacting pairs of genes that affect neuronal survival following elevation in IOP. These data are being evaluated for matches with human disease in the NEIGHBORHOOD genome-wide association datasets.
Using the BXD RI strains, we identified a significant QTL on chromosome 18 that modulates axon loss. This QTL interacts with loci on different chromosomes. We are in the process of identifying gene-gene interactions that in combination may be significant risk factors modulating RGC survival following elevated IOP.
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