Abstract
Defining the master regulators of retinal wound-healing response is the holy grail of transcriptome-wide analyses. To predict regulatory networks, we integrated transcriptome-wide changes with genetic linkage analysis and bioinformatics. Our studies yielded three complementary insights. First, groups of functionally related genes underlie the early, delayed, and sustained responses of wound healing. For example, transcriptional factor upregulation define the early response, whereas glial reactive markers and crystallin family upregulation define the sustained response. Second, expression of a subset of neural development, proliferation, and cell survival genes displayed genetic linkage to a locus that includes positional candidate genes Id2 and Lpin1. Third, mice with a nonfunctional Lipin 1 protein displayed increased ganglion cell survival and crystallin expression after optic nerve crush. The Crystallin Network represents one of the first modulatory mechanisms predicted from expression data of injured retina, expression genetics, and bioinformatics.
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References
Agapova OA, Person E, Harbour JW (2010) Id2 deficiency promotes metastasis in a mouse model of ocular cancer. Clin Exp Metastasis 27:91–96
Chesler EJ, Lu L, Shou S et al (2005) Complex trait analysis of gene expression uncovers polygenic and pleiotropic networks that modulate nervous system function. Nat Genet 37:233–242
Horwitz J (2003) Alpha-crystallin. Exp Eye Res 76:145–153
Inman D, Guth L, Steward O (2002) Genetic influences on secondary degeneration and wound healing following spinal cord injury in various strains of mice. J Comp Neurol 451:225–235
John SW (2005) Mechanistic insights into glaucoma provided by experimental genetics the cogan lecture. Invest Ophthalmol Vis Sci 46:2649–2661
Kempermann G, Gage FH (2002) Genetic influence on phenotypic differentiation in adult hippocampal neurogenesis. Brain Res 134:1–12
Neumann PE, Collins RL (1991) Genetic dissection of susceptibility to audiogenic seizures in inbred mice. Proc Natl Acad Sci USA 88:5408–5412
Peterfy M, Phan J, Xu P et al (2001) Lipodystrophy in the fld mouse results from mutation of a new gene encoding a nuclear protein, lipin. Nat Genet 27:121–124
Piatigorsky J (1998) Multifunctional lens crystallins and corneal enzymes. More than meets the eye. Annals N Y Acad Sci 842:7–15
Rogojina AT, Orr WE, Song BK et al (2003) Comparing the use of Affymetrix to spotted oligonucleotide microarrays using two retinal pigment epithelium cell lines. Mol Vis 9:482–496
Schauwecker PE, Steward O (1997) Genetic determinants of susceptibility to excitotoxic cell death: implications for gene targeting approaches. Proc Natl Acad Sci USA 94:4103–4108
Steele MR, Inman DM, Calkins DJ et al (2006) Microarray analysis of retinal gene expression in the DBA/2J model of glaucoma. Invest Ophthalmol Vis Sci 47:977–985
Templeton JP, Nassr M, Vazquez-Chona F et al (2009) Differential response of C57BL/6J mouse and DBA/2J mouse to optic nerve crush. BMC Neurosci 10:90
Vazquez-Chona F, Song BK, Geisert EE, Jr. (2004) Temporal changes in gene expression after injury in the rat retina. Invest Ophthalmol Vis Sci 45:2737–2746
Vazquez-Chona FR, Lu L, Williams RW et al (2007) Genomic loci modulating the retinal transcriptome in wound healing. Gene regulation and systems biology : 1:327–348
Vazquez-Chona FR, Khan AN, Chan CK et al (2005) Genetic networks controlling retinal injury. Mol Vis [electronic resource] 11:958–970
Willott JF, Erway LC (1998) Genetics of age-related hearing loss in mice. IV. Cochlear pathology and hearing loss in 25 BXD recombinant inbred mouse strains. Hearing Res 119:27–36
Yokota Y, Mori S (2002) Role of Id family proteins in growth control. J Cell Physiol 190:21–28
Acknowledgments
EEG received support from PHS grant RO1EY017841, NIH/NEI Core Grant 5P30 EY13080-04S1, and unrestricted grant from Research to Prevent Blindness. FVC received support from Daniel L. Gerwin Fellowship, Fight For Sight fellowships SF04031 and PD07010, International Retinal Research Foundation (Charles D. Kelman, MD Postdoctoral Scholar award), NIH Training Grant 5T32 HD07491, and Knights Templar Eye Foundation.
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Vázquez-Chona, F.R., Geisert, E.E. (2012). Networks Modulating the Retinal Response to Injury: Insights from Microarrays, Expression Genetics, and Bioinformatics. In: LaVail, M., Ash, J., Anderson, R., Hollyfield, J., Grimm, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 723. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-0631-0_82
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DOI: https://doi.org/10.1007/978-1-4614-0631-0_82
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