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Networks Modulating the Retinal Response to Injury: Insights from Microarrays, Expression Genetics, and Bioinformatics

  • Félix R. Vázquez-ChonaEmail author
  • Eldon E. GeisertEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 723)

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.

Keywords

Retinal injury Neuronal degeneration Genetic networks Crystallin Glaucoma Microarray Lipin 1 QTL analysis Ganglion cell survival 

Notes

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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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of OphthalmologyUniversity of UtahSalt Lake CityUSA
  2. 2.Department of OphthalmologyThe Hamilton Eye Institute University of Tennessee Health Science CenterMemphisUSA

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