Retinal tau pathology in human glaucomas

Abstract

Background: Tau protein is a microtubule-associated protein critical to neuron structure and integrity. The abnormal hyperphosphorylated tau protein AT8 disrupts microtubules, interferes with axonal transport, and is associated with neuron injury in neurodegenerative diseases such as Alzheimer's disease. The purpose of this study was to assess the presence of tau protein and abnormal tau protein AT8 in human glaucomas and to determine whether abnormal tau protein plays a role in glaucomatous neural degeneration. Methods: Sections from 11 surgical eye specimens with glaucoma from elevated intraocular pressure causes and 10 age-matched control eye specimens were immunostained for normal tau protein (BT2) and hyperphosphorylated tau protein (AT8). Postmortem specimens with incidental open-angle glaucoma ( n = 6) were compared with controls ( n = 3). Measurements of immunofluorescence intensity in glaucoma retinas were compared with those in control retinas. Abnormal tau AT8 and parvalbumin, a horizontal cell-specific marker, were studied with double-immunofluorescence techniques to determine colocalization. Results: In surgical glaucoma specimens, normal tau protein was decreased in both the optic nerve and retina compared with age-matched controls. Abnormal tau AT8 was evident within the posterior retina, predominantly at the outer border of the inner nuclear layer in surgical glaucoma specimens, and this was not observed in controls or incidental glaucoma cases. Quantitative immunofluorescence techniques demonstrated significantly increased abnormal tau AT8 in surgical glaucoma specimens compared with controls. Abnormal tau AT8 colocalized with parvalbumin in horizontal cells of the retina. Interpretation: Abnormal tau AT8, a marker of injury in various neurological diseases, is present in human glaucomas with uncontrolled intraocular pressure. The finding of abnormal tau protein in retinal horizontal cells may relate to elevated intraocular pressure and (or) neural degeneration in glaucoma. Tau protein abnormality in glaucoma underscores shared pathways with other neurodegenerative diseases.