Editors' ChoiceGLAUCOMA

Does Inflammation Contribute to Pigmentary Glaucoma?

Science's STKE  06 Sep 2005:
Vol. 2005, Issue 300, pp. tw323
DOI: 10.1126/stke.3002005tw323

In glaucoma, a common cause of blindness, intraocular pressure (IOP) can lead to damage to the optic nerve. Pigmentary glaucoma occurs when pigment shed from the iris pigment epithelium accumulates in and blocks the trabecular meshwork that drains the aqueous humor. Zhou et al. used DBA/2J mice, a model of pigmentary glaucoma, to investigate the role of immune dysfunction in pathogenesis of this disease. Unlike control mice, DBA/2J mice showed an increase in IOP with age, as well as atrophy of the iris and loss of retinal ganglion cells. The authors used quantitative real-time polymerase chain reaction (PCR), reverse transcription PCR, and Western analysis to show increased expression and abundance of interleukin-18 (IL-18, a cytokine implicated in autoimmune and inflammatory diseases) in DBA/2J iris and ciliary body. Immunohistochemistry showed an increase in IL-18 abundance on the anterior chamber side of the iris, whereas enzyme-linked immunosorbent assay revealed an increase in IL-18 abundance in the aqueous humor. IL-18 abundance increased with age, preceding the increase in IOP. Phosphorylation of mitogen-associated protein kinase and translocation to the nucleus of nuclear factor κ B were increased in the iris and ciliary body, indicating activation of these signaling pathways. DBA/2J animals also showed increased abundance of matrix metalloproteinase-2 and increased expression of genes encoding caspase-8, Fas, FADD, FAP, FAF, and TNFRα (all proteins implicated in apoptosis). Immunofluorescence analysis revealed cells positive for CD69, a marker of lymphocye activation, in the iris and anterior chamber. Thus, the authors suggest that an inflammatory or autoimmune response involving IL-18 may be involved in the pathogenesis of pigmentary glaucoma.

X. Zhou, F. Li, L. Kong, H. Tomita, C. Li, W. Cao, Involvement of inflammation, degradation, and apoptosis in a mouse model of glaucoma. J. Biol. Chem. 280, 31240-31248 (2005). [Abstract] [Full Text]