Our group is interested in the response of the retina to injury. Recently we expanded our approach looking at a large segment of the transcriptome using microarrays and bioinformatics. During this process a unique compelling opportunity focused our collective interest on a project looking at retinal axon damage (optic nerve crush) in the mouse as a model system. In collaboration with the Rob Williams'group we are using the BXD recombinant inbred (Rl) strains to define genetic networks in the eye and retina. These interactions have put us in a unique position to study the early signature of retinal injury and genomic loci that may underlie susceptibility or resistance to optic nerve damage. The long-term goal of this project is to define genetic networks controlling susceptibility and resistance of the retina to optic nerve damage and to characterize the early molecular signatures associated with these changes. Our working hypothesis is that the differential vulnerability of the retina is modulated by network of polymorphic genes that contribute to susceptibility or resistance to neurodegeneration and ganglion cell death. We will use a unique set of isogenic strains of mice (the BXD Rl strains) to investigate an experimental model of optic nerve damage. This large set of strains is uniquely suited to study the genetics of optic nerve damage because one of the parental strains is susceptible to injury (DBA/2J strain) whereas the other strain is resistant (C57BL/6 strain). This work exploits the unique properties of this particular strain panel in three specific aims.
Aim 1 will define the normal patterns of transcriptional activity in the retinas of recombinant inbred strains. The transcriptional networks identified in these uninjured mice will serve as a background to define the changes occurring after optic nerve damage.
Aim 2 will test the hypothesis that there are a series of transcriptome signatures in the retina of the BXD Rl strains that are predictive of susceptibility or resistance of ganglion cell death after axon injury. These data will define the common and unique genetic networks that are activated following injury to the optic nerve axons and will define the early changes associated with optic nerve damage. Finally we will be able to identify the genetic networks controlling susceptibility and resistance to ganglion cell death.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Biology and Diseases of the Posterior Eye Study Section (BDPE)
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Agarwal, Neeraj
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University of Tennessee Health Science Center
Anatomy/Cell Biology
Schools of Medicine
United States
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King, Rebecca; Li, Ying; Wang, Jiaxing et al. (2018) Genomic Locus Modulating IOP in the BXD RI Mouse Strains. G3 (Bethesda) 8:1571-1578
Struebing, Felix L; King, Rebecca; Li, Ying et al. (2018) Transcriptional Changes in the Mouse Retina after Ocular Blast Injury: A Role for the Immune System. J Neurotrauma 35:118-129
Lu, Ye; Zhou, Diana; King, Rebecca et al. (2018) The genetic dissection of Myo7a gene expression in the retinas of BXD mice. Mol Vis 24:115-126
Struebing, Felix L; King, Rebecca; Li, Ying et al. (2018) Genomic loci modulating retinal ganglion cell death following elevated IOP in the mouse. Exp Eye Res 169:61-67
Wang, Jiaxing; Struebing, Felix L; Ferdous, Salma et al. (2018) Differential Exon Expression in a Large Family of Retinal Genes Is Regulated by a Single Trans Locus. Adv Exp Med Biol 1074:413-420
Wang, Jiaxing; Li, Ying; King, Rebecca et al. (2018) Optic nerve regeneration in the mouse is a complex trait modulated by genetic background. Mol Vis 24:174-186
Struebing, Felix L; Wang, Jiaxing; Li, Ying et al. (2017) Differential Expression of Sox11 and Bdnf mRNA Isoforms in the Injured and Regenerating Nervous Systems. Front Mol Neurosci 10:354
Struebing, Felix L; Lee, Richard K; Williams, Robert W et al. (2016) Genetic Networks in Mouse Retinal Ganglion Cells. Front Genet 7:169
Bobilev, A M; McDougal, M E; Taylor, W L et al. (2016) Assessment of PAX6 alleles in 66 families with aniridia. Clin Genet 89:669-77
Grossniklaus, Hans E; Geisert, Eldon E; Nickerson, John M (2015) Introduction to the Retina. Prog Mol Biol Transl Sci 134:383-96

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