May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Time Course Analysis of Retinal Transcriptome Changes Following Intravitreal Injection of CNTF, BDNF, and FGF-2
Author Affiliations & Notes
  • X. Liu
    Ophthalmology, Johns Hopkins Univ Sch of Med, Baltimore, Maryland
  • R. Adler
    Ophthalmology, Johns Hopkins Univ Sch of Med, Baltimore, Maryland
  • P. A. Campochiaro
    Ophthalmology, Johns Hopkins Univ Sch of Med, Baltimore, Maryland
  • D. J. Zack
    Ophthalmology, Johns Hopkins Univ Sch of Med, Baltimore, Maryland
  • Footnotes
    Commercial Relationships X. Liu, None; R. Adler, None; P.A. Campochiaro, None; D.J. Zack, None.
  • Footnotes
    Support NEI Grant EY014341; EY1765
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 1348. doi:https://doi.org/
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      X. Liu, R. Adler, P. A. Campochiaro, D. J. Zack; Time Course Analysis of Retinal Transcriptome Changes Following Intravitreal Injection of CNTF, BDNF, and FGF-2. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1348. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose:: To identify the molecular mechanisms by which CNTF, BDNF, and FGF-2 mediate retinal neuroprotection. At the previous ARVO we reported Initial results (ARVO 2006) included identification of several genes that were up-regulated by all 3 factors 6 and 48 hours after intravitreal injection. Immunohistochemistry localized some of the early-induced molecules to Müller glia, macrophage-like cells and/or astrocytes. Building on those findings, we performed additional transcriptional profiling for the 24 hour post-injection time point, and selected a group of genes for more detailed expression studies, with multiple biological replicates and expanded time-course analysis.

Methods:: Adult, wild type C57BL/6J mice received an intravitreal injection of 1ug/ul of either CNTF, BDNF, FGF-2 or vehicle. Animals were sacrificed 1, 6, 12, 24, 48 hours or 1 week post-injection for real time PCR (QPCR), or microarray analysis. RNA harvesting, QPCR and Affymetrix microarray analysis (MOE430_2) were performed by standard methods.

Results:: Microarray analysis of retinal samples 6, 24 and 48 hours post-injection identified several groups of molecules that were up-regulated by growth factors and could be potentially involved in mediating photoreceptor rescue. Among these were: 1) molecules whose mutation is associated with retinopathy (chemokine (C-C motif) ligand 2, dystrophin); 2) neuronal survival promoting factors (endothelin 2, interleukin 6, leukemia inhibitory factor); 3) growth factor receptors and modulators (oncostatin M receptor, suppressor of cytokine signaling; 4) interferon-induced molecules (interferon-induced transmembrane protein 3); 5) transcription factors (C/EBP delta, signal transducer and activator transcript 3); and 6) ion regulating molecules (ceruloplasmin, transferrin, lipocalin 2, metallothionein 2). QPCR showed characteristic time-courses of induction for different members of these families of molecules.

Conclusions:: Analysis of genes modulated by the intravitreal injection of CNTF, BDNF, and FGF-2 suggest the involvement of membrane stabilization, immunoregulation, and cytoskeletal modulation in growth factor-mediated retinal neuroprotection.

Keywords: cytokines/chemokines • growth factors/growth factor receptors • neuroprotection 
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