Abstract
Cellular communication is an essential process for the development and maintenance of all tissues including the eye. Recently, a new method of cellular communication has been described, which relies on formation of tubules, called tunneling nanotubes (TNTs). These structures connect the cytoplasm of adjacent cells and allow the direct transport of cellular cargo between cells without the need for secretion into the extracellular milieu. TNTs may be an important mechanism for signaling between cells that reside long distances from each other or for cells in aqueous environments, where diffusion-based signaling is challenging. Given the wide range of cargoes transported, such as lysosomes, endosomes, mitochondria, viruses, and miRNAs, TNTs may play a role in normal homeostatic processes in the eye as well as function in ocular disease. This review will describe TNT cellular communication in ocular cell cultures and the mammalian eye in vivo, the role of TNTs in mitochondrial transport with an emphasis on mitochondrial eye diseases, and molecules involved in TNT biogenesis and their function in eyes, and finally, we will describe TNT formation in inflammation, cancer, and stem cells, focusing on pathological processes of particular interest to vision scientists.
Highlights
Cells have numerous mechanisms of communication in order to develop normally, repair wounds, and respond to inflammation
Other groups subsequently showed the intercellular transfer of mitochondria and endocytic vesicles derived from early endosomes, the Golgi complex, endoplasmic reticulum, and lysosomes [15,16,17,18,19,20]
It is possible that direct connections via tunneling nanotubes (TNTs) were involved in this mitochondrial transfer, but the thin tubules may have been destroyed during the harsh fixation treatments used in the preparation procedures used for electron microscopy
Summary
Cells have numerous mechanisms of communication in order to develop normally, repair wounds, and respond to inflammation Many of these mechanisms rely on secretion of signals from one cell, diffusion through the extracellular milieu, and uptake by a target cell, which may be located far from the secretory cell. Two more recent modes of communication are described: cytonemes and tunneling nanotubes (TNTs) (Figure 2). These cellular structures allow signaling over long distances by providing direct connections between cells, which overcomes many challenges of diffusion-based signaling [2,3,4,5,6,7]. We will first describe (1) the current knowledge of TNTs in the mammalian eye, (2) the role of TNTs in mitochondrial transfer with an emphasis on eye disease, (3) TNT molecular regulators and their function in eyes, and (4) the role of TNTs in other diseases that are of interest to vision researchers
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