Abstract
Purpose::
Progressive visual loss in glaucoma results from an optic neuropathy characterized by apoptotic death of retinal ganglion cells (RGCs). While little is known about the mechanism of how and why RGCs die, recent reports suggest that this mechanism might be due to an accumulation of neurotoxic proteins such as those found in Alzheimer’s disease. In this study, we tested the hypothesis that protein markers of Alzheimer’s disease (ß-amyloid, α-synuclein, and phosphorylated tau) are elevated in glaucoma eyes.
Methods::
Formalin-fixed, paraffin-embedded tissue samples of whole eyes were obtained from the Department of Pathology, consisting of a control group without glaucoma (n = 9) and an experimental group with glaucoma (n = 8). Eyes with concomitant diagnosis of uveitis, scleritis, tumor, as well as any posterior segment diseases (such as non-glaucomatous optic neuropathy, diabetic retinopathy, or macular degeneration, etc) were excluded. Immunostaining was performed for ß-amyloid, phosphorylated-tau, and α-synuclein. Staining intensity was graded in a masked fashion, and the results were analyzed for statistical significance.
Results::
We evaluated staining intensities and patterns for each of the three protein markers at the nerve fiber layer, sclera, choroid, and optic nerve head (prelaminar, laminar, and retrolaminar portions). While similar levels of expression of ß-amyloid and α-synuclein were observed in both groups, phosphorylated-tau protein was expressed at higher levels in glaucomatous eyes. This differenial expression of phosphorylated-tau was specifically localized to the retrolaminar region of the optic nerve head (p < 0.05).
Conclusions::
Immunostaining of human eye pathology sections showed differential expression of phosphorylated-tau, which was elevated in glaucomatous eyes in the retrolaminar region of the optic nerve head. This suggests that phosphorylated-tau, implicated in the pathogenesis of Alzheimer’s disease, may also play a role in the development of glaucomatous optic neuropathy. Further work is required to elucidate the relationship between phophorylation of the tau protein and RGC apoptosis in glaucoma.
Keywords: optic nerve • ganglion cells • pathology: human