Abstract

The potential of stem cell (SC) therapies for eye diseases is well-recognized. However, the results remain only encouraging as little is known about the mechanisms responsible for eye renewal, regeneration and/or repair. Therefore, it is critical to gain knowledge about the specific tissue environment (niches) where the stem/progenitor cells reside in eye. A new type of interstitial cell–telocyte (TC) (http://www.telocytes.com) was recently identified by electron microscopy (EM). TCs have very long (tens of micrometres) and thin (below 200 nm) prolongations named telopodes (Tp) that form heterocellular networks in which SCs are embedded. We found TCs by EM and electron tomography in sclera, limbus and uvea of the mouse eye. Furthermore, EM showed that SCs were present in the anterior layer of the iris and limbus. Adhaerens and gap junctions were found to connect TCs within a network in uvea and sclera. Nanocontacts (electron-dense structures) were observed between TCs and other cells: SCs, melanocytes, nerve endings and macrophages. These intercellular ‘feet’ bridged the intercellular clefts (about 10 nm wide). Moreover, exosomes (extracellular vesicles with a diameter up to 100 nm) were delivered by TCs to other cells of the iris stroma. The ultrastructural nanocontacts of TCs with SCs and the TCs paracrine influence via exosomes in the epithelial and stromal SC niches suggest an important participation of TCs in eye regeneration.

Highlights

  • The potential of stem cell (SC) therapies for eye diseases is wellrecognized even the results remain only encouraging [1,2,3,4,5,6,7].Recently, telocytes (TCs) have been described as a new type of interstitial cell by electron microscopy [8,9,10]

  • Limbus seems to be rich in undifferentiated pluripotent cells which serve as an important source of new corneal epithelium [26,27,28,29,30] and a stem-cell niche has been described at this level [24]

  • Ultrastructural analysis was performed on all three tunics of mouse eye (Fig. 1): fibrous, vascular pigmented and nervous

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Summary

Introduction

Telocytes (TCs) have been described as a new type of interstitial cell by electron microscopy [8,9,10]. Adult tissue SCs are undifferentiated cells, capable of proliferation, self-renewal and differentiation into different tissue-specific progeny. Little is known about the cellular mechanisms responsible for eye renewal, regeneration and/or repair in situ but SCs and progenitor cells have been described in different areas of the eye [22,23,24,25]. Limbus seems to be rich in undifferentiated pluripotent cells which serve as an important source of new corneal epithelium [26,27,28,29,30] and a stem-cell niche has been described at this level [24]

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