Purchase this article with an account.
Franklin Echevarria, Michelle Won, Caroline Walker, Heather Cathcart, Rebecca Sappington; gp130 Expression and Activation as a Function of Age and IOP in the DBA/2 Mouse Model of Glaucoma. Invest. Ophthalmol. Vis. Sci. 2013;54(15):755.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To identify potential avenues of interkeukin-6 (IL-6) and related cytokine signaling in glaucomatous retina, we examined age- and IOP-related changes in expression and activation of the IL-6-family signal transducer gp130.
Using immunoassay and qPCR, we measured global expression of gp130 in 4 and 8 month old DBA/2 and C57/Bl6 mice. Ganglion cell- and nerve fiber layer-specific expression in these mice was quantified using immunohistochemistry and quantitative digital microscopy. Co-immunolabeling of gp130 and cell type-specific markers was used to identify potential targets of signaling from members of the IL-6 family of cytokines and correlate gp130 expression with cell loss in retinal ganglion cells (RGCs). Cell types evaluated included: retinal ganglion cells (RGCs; brn3a and β-Tubulin III), astrocytes (GFAP) and Müller cells (glutamine synthetase). To measure gp130 activation, we quantified phosphorylation of STAT3, the downstream target of gp130 signaling, by immunoblotting.
Global expression of gp130 increases by 10 fold in aged C57 mice, compared to young C57 (p<0.05). In contrast, there is no age- or IOP-related change in gp130 expression in DBA/2 mice (p>0.05). However, gp130 expression in DBA/2 mice is ~50% less than age-matched C57 mice (p<0.05). Protein localization studies reveal co-localization of gp130 primarily with RGC and Müller cell markers in the ganglion cell (GCL) and nerve fiber (NFL) layers of the retina. Expression of gp130 in the GCL/NFL increases by ~64% in the peripheral retina of aged C57 mice, compared to young C57 mice. There are no IOP or age-related changes in the peripheral GCL/NFL of DBA/2 mice (p>0.05) or the central GCL/NFL of either strain (p>0.05). Interestingly, the overall number of gp130/brn3a+ RGCs increases by ~20% in DBA/2 retina, as compared to age-matched C57 retina (p<0.05). Despite little to no change in gp130 expression, activation of Stat3 was elevated by as much as 3 fold in DBA/2 mice, compared to C57 mice.
Our data suggests that global changes in gp130 expression are associated with normal aging, while aging in the presence of elevated IOP induces discreet changes in gp130 expresssion, specifically in RGCs. This increase in gp130 expression by RGCs is accompanied by an increase in STAT3 activation, suggesting that RGCs are a primary target of gp130-mediated signaling induced by glaucomatous stressors.
This PDF is available to Subscribers Only