Effects of glaucoma on chrna6 expression in the retina

Gustavo C. Munguba, Eldon E. Geisert, Robert W. Williams, Mary L. Tapia, Daisy K. Lam, Sanjoy K. Bhattacharya, Richard K. Lee

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Purpose: Recent advances in technology now provide tools capable of tracking genome-wide expression changes occurring in progressive pathological processes. The present experiments were carried out to determine if acetylcholine receptor α 6 subunit (Chrna6) is a reliable retinal ganglion cell (RGC) marker in adult mouse eyes and if Chrna6 expression can be used to track progressive loss of RGCs, such as is observed in the DBA/2J glaucoma model. Methods: Data sets derived from the BXD strains were used to extract gene expression signatures for RGCs. Pooled retinas from DBA/2J or C57BL/6J cases at 1-3 months, 12 months, and 16-17 months were prepared for gene-array and RT-PCR analysis. Globes were fixed in paraformaldehyde and sectioned for immunofluorescence with antibodies against Chrna6. Results: Chrna6 has a cellular expression signature for RGCs with high correlation to Thy1 (r = 0.65), a recognized RGC marker. Immunofluorescence experiments confirm that in the young and adult mouse retina, Chrna6 is preferentially expressed by RGCs. We further show that C3H/HeJ retinas, which lack photoreceptors, also express Chrna6 in the RGC layer. Gene expression array analyses, confirmed by RT-PCR, show progressive loss of Chrna6 expression in retinas of the DBA/2J glaucomatous mouse retinas. Conclusions: Quantitative trait locus analysis provides support for Chrna6 as a RGC marker. Chrna6 expression decreases with death of RGCs in glaucomatous DBA/2J mice and after optic nerve crush injury, further supporting Chrna6 as a reliable RGC marker. High expression of RGC Chrna6 in the absence of photoreceptors is suggestive that Chrna6 expression by RGCs is independent of photoreceptor-derived stimuli.

Original languageEnglish (US)
Pages (from-to)150-157
Number of pages8
JournalCurrent Eye Research
Volume38
Issue number1
DOIs
StatePublished - Jan 1 2013

Keywords

  • Aging
  • Gene Network
  • Glaucoma
  • Neurodegenerative Diseases
  • QTL
  • Retina

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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  • Cite this

    Munguba, G. C., Geisert, E. E., Williams, R. W., Tapia, M. L., Lam, D. K., Bhattacharya, S. K., & Lee, R. K. (2013). Effects of glaucoma on chrna6 expression in the retina. Current Eye Research, 38(1), 150-157. https://doi.org/10.3109/02713683.2012.724512