May 2006
Volume 47, Issue 13
ARVO Annual Meeting Abstract  |   May 2006
Potential Impact of Glial Hypertrophy and Proteoglycan Changes on Retinal Ganglion Cell Function in the DBA/2 Mouse Model of Glaucoma
Author Affiliations & Notes
  • D. Inman
    Neurological Surgery, University of Washington, Seattle, WA
  • P.J. Horner
    Neurological Surgery, University of Washington, Seattle, WA
  • Footnotes
    Commercial Relationships  D. Inman, None; P.J. Horner, None.
  • Footnotes
    Support  Glaucoma Research Foundation Catalyst for a Cure
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 1576. doi:
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      D. Inman, P.J. Horner; Potential Impact of Glial Hypertrophy and Proteoglycan Changes on Retinal Ganglion Cell Function in the DBA/2 Mouse Model of Glaucoma . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1576.

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

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Purpose: : Retinal ganglion cells undergo profound changes in the course of glaucoma, including dendritic process retraction and axon degeneration. Gliosis in the nerve fiber layer (NFL) involving astrocytes and Müller glia precedes many glaucomatous ganglion cell changes. These experiments examine neural–glial interactions in the DBA/2 mouse model of glaucoma, demonstrating how the hypertrophy of glia and factors secreted or expressed by astrocytes and Müller glia, such as proteoglycans, impact the ganglion cells.

Methods: : Proteoglycans and glial intermediate filaments were examined in the DBA/2 retina at different ages and intraocular pressure (IOP) levels through immunohistochemistry, RT–PCR and Western blotting.

Results: : Glial hypertrophy is detectable through RT–PCR and Western blot for glial fibrillary acidic protein (GFAP) by 5 months of age in the DBA/2 retina and it continues to intensify with increasing IOP. Coincident with GFAP upregulation is increased chondroitin sulfate proteoglycan immunolabel on Müller glia somas and basal processes. Müller glia numbers are stable through 12 months of raised IOP in DBA/2 mice, as are Müller–specific transcripts such as cellular retinaldehyde binding protein (CRALBP) and the glutamate–aspartate transporter (GLAST). By RT–PCR and immunohistochemistry, several proteoglycans, neurocan and syndecan–1 in particular, increase with increasing IOP in the DBA/2 retina. Antibodies against neurocan and phosphacan labeled some inner retinal vasculature in DBA/2 mice at young ages and normal IOP but were observed labeling retinal ganglion cell somas as early as 5 months in mice with high IOP.

Conclusions: : Sustained gliosis and increases in proteoglycan mRNA and protein levels can have a profound effect on neuronal–glial signaling in the retina. Neurocan, inhibitory to neurite outgrowth, is upregulated in retinal ganglion cells and may prevent these cells from maintaining or making new connections during glaucoma progression.

Keywords: Muller cells • proteoglycans/glycosaminoglycans • retina: proximal (bipolar, amacrine, and ganglion cells) 

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