Abstract:
:The present study was designed to identify genomic loci modulating the susceptibility of retinal ganglion cells (RGC) to elevated intraocular pressure (IOP) in the BXD recombinant inbred mouse strain set. IOP was elevated by injecting magnetic microspheres into the anterior chamber and blocking the trabecular meshwork using a handheld magnet to impede drainage. 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 used in this study. On day 21, mice were sacrificed and the optic nerve was processed for histology. Axons were counted for both the injected and the control eye in 49 BXD strains, totaling 181 normal counts and 191 counts associated with elevated IOP. The axon loss for each strain was calculated and the data were entered into genenetwork.org. The average number of normal axons in the optic nerve across all strains was 54,788 ± 16% (SD), which dropped to 49,545 ± 20% in animals with artificially elevated IOP. Interval mapping demonstrated a relatively similar genome-wide map for both conditions with a suggestive Quantitative Trait Locus (QTL) on proximal Chromosome 3. When the relative axon loss was used to generate a genome-wide interval map, we identified one significant QTL (p < 0.05) on Chromosome 18 between 53.6 and 57 Mb. Within this region, the best candidate gene for modulating axon loss was Aldh7a1. Immunohistochemistry demonstrated ALDH7A1 expression in mouse RGCs. ALDH7A1 variants were not significantly associated with glaucoma in the NEIGHBORHOOD GWAS dataset, but this enzyme was identified as part of the butanoate pathway previously associated with glaucoma risk. Our results suggest that genomic background influences susceptibility to RGC degeneration and death in an inducible glaucoma model.
journal_name
Exp Eye Resjournal_title
Experimental eye researchauthors
Struebing FL,King R,Li Y,Cooke Bailey JN,NEIGHBORHOOD consortium.,Wiggs JL,Geisert EEdoi
10.1016/j.exer.2017.12.013subject
Has Abstractpub_date
2018-04-01 00:00:00pages
61-67eissn
0014-4835issn
1096-0007pii
S0014-4835(17)30660-7journal_volume
169pub_type
杂志文章abstract::This study was conducted to evaluate the impact of varying scleral material properties on the biomechanical response of the cornea under air-puff induced deformation. Twenty pairs of human donor eyes were obtained for this study. One eye from each pair had its sclera stiffened using 4% glutaraldehyde, while the fellow...
journal_title:Experimental eye research
pub_type: 杂志文章
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journal_title:Experimental eye research
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journal_title:Experimental eye research
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journal_title:Experimental eye research
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journal_title:Experimental eye research
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journal_title:Experimental eye research
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journal_title:Experimental eye research
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journal_title:Experimental eye research
pub_type: 杂志文章
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journal_title:Experimental eye research
pub_type: 杂志文章
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journal_title:Experimental eye research
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journal_title:Experimental eye research
pub_type: 杂志文章
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journal_title:Experimental eye research
pub_type: 杂志文章
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journal_title:Experimental eye research
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journal_title:Experimental eye research
pub_type: 杂志文章
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journal_title:Experimental eye research
pub_type: 杂志文章
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journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2007.07.019
更新日期:2007-11-01 00:00:00
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journal_title:Experimental eye research
pub_type: 杂志文章
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journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2008.10.029
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journal_title:Experimental eye research
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journal_title:Experimental eye research
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journal_title:Experimental eye research
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journal_title:Experimental eye research
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journal_title:Experimental eye research
pub_type: 杂志文章
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journal_title:Experimental eye research
pub_type: 杂志文章,评审
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更新日期:2017-10-01 00:00:00
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journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1006/exer.1996.0036
更新日期:1996-03-01 00:00:00
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journal_title:Experimental eye research
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journal_title:Experimental eye research
pub_type: 杂志文章
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journal_title:Experimental eye research
pub_type: 杂志文章
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更新日期:2013-08-01 00:00:00
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journal_title:Experimental eye research
pub_type: 杂志文章
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