Purchase this article with an account.
K. M. Coxon, J. Duggan, S. Nizari, L. Guo, M. F. Cordeiro; Effects of Ocular Hypertension on Tumor Necrosis (TNF) Receptors and RGC Apoptosis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2124.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Although tumor necrosis factor-alpha (TNF-α) has been shown to be involved in glaucoma, particularly at the optic nerve head, the role of its receptors (TNF-R1 and -R2) is less well established. RGC death has been shown to occur through TNF-R1-mediated caspase activation, mitochondrial dysfunction, and oxidative stress. In this study, we investigated changes in TNF-R1 and -R2 over time and in relation to RGC apoptosis in an OHT rat model.
Using our established chronic ocular hypertension (OHT) rat model, IOP was induced in 12 animals, with DARC imaging performed at 1, 3 and 12 weeks after IOP elevation, with animals sacrificed immediately after. Unoperated eyes were used as controls. Immunohistological analysis of TNF-R1 (Abcam ab58436 & ab19139) and -R2 (Abcam ab15563) expression was performed on sequential 5 µm thick paraffin sections from enucleated eyes (n=4 per time point), with grading done by masked observers, as previously described.
DARC imaging recorded peak RGC apoptosis in OHT eyes at 3 weeks as previously described. Immunohistological assessment showed increasing expression of TNF-R1 in RGC layer after IOP elevation, reaching a significant peak at 3 weeks with both TNF-R1 antibodies in all OHT eyes compared to control (p<0.05). In contrast, there was no difference over time in expression of TNF-R2.
Changes in TNF-R1 appear to follow a similar profile to the development of RGC apoptosis in this experimental model of glaucoma. TNF-R1 activity appears maximal at the time of peak RGC apoptosis activity (3 weeks). This agrees with previous work suggesting that TNF-R1 augments RGC death whilst TNF-R2 may be neuroprotective.
This PDF is available to Subscribers Only