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Editors Selection IGR 15-4

Genetics: Gene expression in RGC

Comment by Rand Allingham on:

19282 Disease gene candidates revealed by expression profiling of retinal ganglion cell development, Wang JT; Kunzevitzky NJ; Dugas JC et al., Journal of Neuroscience, 2007; 27: 8593-8603

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In this fascinating paper, Wang et al. (891) study the gene expression patterns of highly purified retinal ganglion cells (RGCs) in rats at 13 separate ages from embryonic day 17 through postnatal day 21. Several important observations are reported. First, 28 genes were identified that were expressed at least 20 fold greater in RGCs than with total retina. Second, gene expression patterns in RGCs aged in vivo vary greatly from changes of RGCs aged in vitro. Third, over half (65%) of genes regulated during development and after axotomy plus lens injury, a model of axonal regrowth, are regulated inversely in these two conditions so may be useful for studies of developmental and regenerative axon growth. Fourth, the investigators found striking changes in gene expression within this perinatal time frame. Hierarchical cluster analysis revealed gene clusters that decreased perinatally, clusters that increased perinatally, and a cluster of genes that spike at birth and then returned to lower levels after the first postnatal week. Finally, and interestingly, three genes associated with glaucoma, CYP1B1, optineurin, and cochlin, were expressed by RGCs. Optineurin and cochlin were both upregulated during development whereas CYP1B1 was downregulated. This data illustrates the complex and profound molecular processes that occur during early RGC development. The observations contained will be valuable for investigations of RGC biology including studies of axonal regrowth, regeneration of RGCs, and incites into currently known and potentially new candidate genes for glaucoma and other retina disorders.

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