QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, March 12, 2008, 28(11):2735-2744; doi:10.1523/JNEUROSCI.4443-07.2008

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Buckingham, B. P. Articles by Horner, P. J. PubMed PubMed Citation Articles by Buckingham, B. P. Articles by Horner, P. J.

 Previous Article  |  Next Article 

Neurobiology of Disease
Progressive Ganglion Cell Degeneration Precedes Neuronal Loss in a Mouse Model of Glaucoma

Brian P. Buckingham,^1 * Denise M. Inman,^1 * Wendi Lambert,¹ Ericka Oglesby,^4,5 David J. Calkins,² Michael R. Steele,³ Monica L. Vetter,³ Nicholas Marsh-Armstrong,^4,5 and Philip J. Horner¹

¹Department of Neurological Surgery, University of Washington, Seattle, Washington 98104, ²Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, Tennessee 37232, ³Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, Utah 84132, ⁴Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, and ⁵Kennedy Krieger Institute, Baltimore, Maryland 21205

Correspondence should be addressed to Philip J. Horner, Department of Neurological Surgery, 325 9th Avenue, Box 359655, Seattle, WA 98104. Email: phorner{at}u.washington.edu

Glaucoma is characterized by retinal ganglion cell (RGC) pathology and a progressive loss of vision. Previous studies suggest RGC death is responsible for vision loss in glaucoma, yet evidence from other neurodegenerative diseases suggests axonal degeneration, in the absence of neuronal loss, can significantly affect neuronal function. To characterize RGC degeneration in the DBA/2 mouse model of glaucoma, we quantified RGCs in mice of various ages using neuronal-specific nuclear protein (NeuN) immunolabeling, retrograde labeling, and optic nerve axon counts. Surprisingly, the number of NeuN-labeled RGCs did not decline significantly until 18 months of age, at which time a significant decrease in RGC somal size was also observed. Axon dysfunction and degeneration occurred before loss of NeuN-positive RGCs, because significant declines in RGC number assayed by retrograde tracers and axon counts were observed at 13 months. To examine whether axonal dysfunction/degeneration affected gene expression in RGC axons or somas, NeuN and neurofilament-heavy (NF-H) immunolabeling was performed along with quantitative reverse transcription-PCR for RGC-specific genes in retinas of aged DBA/2 mice. Although these mice had similar numbers of NeuN-positive RGCs, the expression of neurofilament light, Brn-3b, and Sncg mRNA varied; this variation in RGC-specific gene expression was correlated with the appearance of NF-H immunoreactive RGC axons. Together, these data support a progression of RGC degeneration in this model of glaucoma, beginning with loss of retrograde label, where axon dysfunction and degeneration precede neuronal loss. This progression of degeneration suggests a need to examine the RGC axon as a locus of pathology in glaucoma.

Key words: RGC; death; axon; degeneration; optic nerve; axon

---

Received May 16, 2007; revised Jan. 6, 2008; accepted Jan. 7, 2008.

Correspondence should be addressed to Philip J. Horner, Department of Neurological Surgery, 325 9th Avenue, Box 359655, Seattle, WA 98104. Email: phorner{at}u.washington.edu

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help