Telocytes and stem cells in limbus and uvea of mouse eye

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.

Telocytes in normal and keratoconic human cornea: an immunohistochemical and transmission electron microscopy study

“…As far as the ocular system is concerned, a recent report described the presence of TC in the limbus, sclera and uvea of the mouse eye 50. However, to the best of our knowledge, no study has yet described the presence of TC in the human eye and in particular, within the stromal compartment of the cornea.…”

Mini-Review: Limbal Stem Cells Deficiency in Companion Animals: Time to Give Something Back?

“…The niches are also reported to contain Langerhan's cells (Baum JL 1970) and T-lymphocytes (Vantrappen L et al 1985). In addition, recent studies in mice described the presence of a novel type of interstitial cell called telocytes in association with stem cell niches that also contain nerve endings in addition to blood vessels (Luesma MJ et al 2013). The niches in humans were shown to contain putative LESC in areas described as limbal crypts and focal stromal projections, which showed a regional variation around the limbus with a predominant localization in the superior and inferior corneal quadrants and absence nasally and temporally (Shortt AJ et al 2007;Dziasko et al 2014).…”

“…One study in equines suggests the palisades are not visible in horses (Moriyama H et al 2014). Palisades and niches have been described in mice and pigs but the authors did not indicate if they could be directly observed with slit lamp biomicroscopy (Notara et al 2011, Luesma MJ et al 2013. Until the microstructure of the limbus of domestic, and in particular, companion animals is studied and described in the same detail as the limbus of humans, the significance of interspecies similarities and differences remains unknown.…”

“…Some of this research has used corneal tissues of rodents and rabbits (Kinoshita S et al 1981, Nagasaki T et al 2003, Kadar T et al 2011, Das P et al 2013, Luesma MJ et al 2013, bovines (Sun et al 2006), pigs (Notara M et al 2011), dogs (Wood JA et al 2012) and even goats (Yin JQ et al 2013). Yet, as the focus of these studies are humans, our understanding of the anatomy and physiology of healthy corneal epithelial stem cells in most animal species is rather poor, and it is practically inexistent in disease.…”

Morphological Evidence of Telocytes in Canine Inferior Vena Cava

“…TC, a particular identified type of stromal cell, has been identified morphologically by a small cell body and specific long prolongations called Telopodes (Tp) alternating thin segments (podomers) with dilations (podoms) [3]. TCs have been described in various organs and tissues, such as spleen [4], skin [5], esophagus [6], parotid gland [7], salivary glands [8], endocardium [9], bone marrow [10], pleura [11], vasculature [12], lung [13], duodenum [14], liver [15], eye [16], cardiac valves [17], uterus [18], et al Although TCs were also identified in large arteries [19], whether TCs exist in large veins was not yet reported. Here, the ultrastructural features of TCs in inferior vena cava were, for the first time, clarified under transmission electron microscope (TEM).…”