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Editors Selection IGR 12-2

Basic research: Hyperphosphorylated tau

Comment by Stuart McKinnon on:

20304 Retinal tau pathology in human glaucomas, Gupta N; Fong J; Ang LC et al., Canadian Journal of Ophthalmology, 2008; 43: 53-60

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Although the mechanisms of RGC death are not completely understood, recent studies have shown that glaucoma shares similarities with other chronic neurodegenerations. Disruption of axonal transport in retinal ganglion cells (RGCs) is an early marker of neuronal dysfunction in glaucoma. An important element of axonal transport involves the microtubule-associated protein tau, and abnormal phosphorylation of tau has been linked to neuronal dysfunction in a number of neurode-generations. Gupta et al. (79) have examined the immunohistochemical expression of normal and hyperphosphorylated tau in post-mortem human retina and optic nerves. Eyes with a history of uncontrolled IOP and optic nerve head excavation were included, as well as age-matched control eyes. A second group with an 'incidental' diagnosis of presumably controlled POAG was also examined. Immunolabeling was performed with the primary antibodies BT2 (recognizing normal tau) and AT8 (recognizing hyperphosphorylated tau). In control eyes, normal tau labeling was seen in the inner nuclear, inner plexiform, RGC and nerve fiber layers, and in pre- and post-laminar optic nerves. Significantly less normal tau labeling was seen in retinas and optic nerves of uncontrolled glaucoma eyes. Immunolabeling in controlled glaucoma eyes did not differ from age-matched controls. In contrast, hyperphosphorylated tau immunolabeling in uncontrolled glaucoma eyes was significant in the outer border of the inner nuclear layer, and was colocalized by parvalbumin staining to horizontal cells. Control and incidental glaucoma retinas, as well as control and all glaucoma optic nerves, displayed little to no hyperphosphorylated tau immuno-labeling. The presence of hyperphosphorylated tau in horizontal cells in glaucomatous retinas is a novel finding and adds more evidence linking glaucoma with other chronic neurodegenerations.

The AT8 antibody did not label the nerve fiber layer or optic nerve of uncontrolled glaucoma eyes, the major microtubule-containing structures in which one would expect to find abnormal tau protein. However, AT8 recognizes a single phosphorylated serine residue, and other tau serines are known to be phosphorylated. We anticipate further studies to fully characterize the localization of abnormal tau in retinas and optic nerves affected by glaucoma.

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