Specific expression of E-Tmod (Tmod1) in horizontal cells: implications in neuronal cell mechanics and glaucomatous retina.

Erythrocyte tropomodulin (E-Tmod) is a tropomyosin-binding and actin capping protein at the point end of the filaments. It is part of a molecular ruler that plays an important role in generating short actin protofilaments critical for the integrity of the cell membrane. Here, with the use of E-Tmod+/lacZ mice, we demonstrated a specific E-Tmod expression in horizontal cells (HCs) in the retina, and analyzed the stress-strain relationship of HCs, vertically oriented neurons, and retinal ganglial cells (RGC) under normal and high intraocular pressure (IOP). Since their dendrites are oriented laterally in a plane and form most complicated synapses with multiple cone photoreceptors, HCs are subjected to a greater stress and strain than vertically oriented neurons. The specific E-Tmod expression suggests its role in protecting HCs from mechanical damages in certain eye diseases, such as glaucoma, a neurodegenerative disease of the retina characterized by an elevated IOP. A stress-strain analysis on axons of RGC that run horizontally but only anchor at the optical nerve head suggests that they may also be subjected to a higher mechanical stress, which leads to an increase in "cup-to-disc" ratio in a higher IOP or in glaucoma patients.