Ocular MECP2 protein expression in patients with and without Rett syndrome

Rett syndrome is a neurodevelopmental disorder caused by mutations in the methyl CpG binding protein 2 gene (MECP2). The MECP2 protein is expressed primarily in neurons, and mutations in the gene lead to the clinical features of Rett syndrome in human patients and neurologic deficits in murine models. Visual function is relatively preserved in Rett syndrome patients, but the cause is unknown. The eyes of two Rett syndrome patients who died of the disease were analyzed; no gross or microscopic changes were found. MECP2 expression was examined using immunohistochemistry; nuclear protein expression was largely limited to ganglion cells and the portion of the inner nuclear layer populated by amacrine cells. No significant differences in MECP2 protein level or distribution were identified in the two eyes from the Rett syndrome patients, compared with 11 controls. The findings were compared with MECP2 expression in the brain of these two subjects and in MECP2-deficient mice. The findings suggest that the normally limited expression of MECP2 in visual pathway neurons may underlie the intact vision observed in Rett syndrome.