Parallels between neuron and lens fiber cell structure and molecular regulatory networks

Studies over the past fifty years have identified extensive similarities between neurons and elongated fiber cells that make up in the interior of the ocular lens. Electron micrographs showed parallels in the organization of their intracellular vesicle transport machinery and between lens fiber cell lateral protrusions and dendritic spines. Consistent with those observations, a number of gene products first characterized as highly neuron-preferred in their expression were also demonstrated in lens fiber cells. Going further, a fundamental network of regulatory factors with critical roles in determining the neuronal phenotype were also identified in lenses, and showed a corresponding mutually exclusive distribution of neural and non-neural factor isoforms in mitotic lens epithelial cells and post-mitotic fiber cells consistent with their interlocking functions in neural cells. These included REST/NRSF transcription factors, members of major RNA binding protein families, and “brain-specific” miRNAs that were each shown to have global roles in governing neural and non-neural gene expression and alternative transcript splicing in vertebrates. This review discusses these extensive parallels between neurons and fiber cells and implications regarding common themes in lens and neural cell physiology and disease, which may also suggest related evolutionary processes.

► Elongated neuron and lens fiber cells show similar surface and sub‐cellular organization. ► The REST/NRSF molecular regulatory network is also present in the lens. ► Major classes of neural RNA binding proteins are present in lens fiber cells. ► miRNAs linked with dendritic spines construction are also expressed in lenses. ► REST/NRSF regulated AMPA receptor GluA2 expression is shared in lenses.