Microtubule alterations may destabilize photoreceptor integrity age-related microtubule changes and pattern of expression of MAP-2, Tau and hyperphosphorylated Tau in aging human photoreceptor cells.

Abstract Photoreceptor cells undergo changes with aging. It is unknown if their microtubules are stable or not with aging. This study examined photoreceptor cell ultrastructure from 18 human donor retinas (32 eyes; age: 45–94 years) and quantified the photoreceptors with altered microtubules over six to ninth decades in four defined retinal regions. In addition, immunoreactivity (IR) to microtubule-associated protein-2 (MAP-2), tau and hyperphophorylated tau was performed in retinal sections from companion eyes. In young donor retinas below 75 years of age, microtubules appeared straight in photoreceptor inner segments and axons. With age, they appeared bent or misaligned in macular and mid-peripheral photoreceptors. In addition, dense granular materials were present in photoreceptor axons and synaptic terminals in advanced ages. In all decades, rod microtubules were affected more than their cone counterparts (28% vs 15%, p  75 years). IR to hyperphosphorylated tau was present mainly in inner retina and increased with aging. Markers of oxidative stress, e.g., lipid peroxidation (4-hydroxy 2-nonenal) and nitrosative stress (nitrotyrosine) were immunopositive in aged photoreceptors. The sporadic loss of MAP-2 and tau-IR in photoreceptors may be due to microtubule changes; all these changes may affect intracellular transport and be partly responsible for photoreceptor death in aged human retina.