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

Abstract

Telocytes (TC) are typically defined as cells with telopodes by their ultrastructural features. Their presence was reported in the interstitium of various organs in vertebrates, including humans. However, no study has yet described the presence of TC in the human eye and in particular, within the stromal compartment of the cornea. To address this issue, samples of normal and pathologic (keratoconic) human corneas were tested by immunohistochemistry for CD34, platelet‐derived growth factor receptor α (PDGFRα) and c‐kit/CD117 or examined by transmission electron microscopy. We found that TC coexpressing CD34 and PDGFRα were distributed throughout the whole normal corneal stroma with different TC subtypes being distinguishable on the basis of the expression of the stemness marker c‐kit (i.e. c‐kit‐positive and c‐kit‐negative TC subpopulations). Transmission electron microscopy examination confirmed the existence of spindle‐shaped and bipolar TC typically displaying two long and thin moniliform telopodes establishing intercellular contacts formed by gap junctions. Keratoconic corneas were characterized by ultrastructural damages and patchy loss of TC with an almost complete depletion of the c‐kit‐positive TC subpopulation. We propose that TC may contribute to the maintenance of corneal stromal homoeostasis and that, in particular, the c‐kit‐positive TC subtype might have stemness capacity participating in corneal regeneration and repair processes. Further studies are needed to clarify the differential roles of corneal TC subtypes as well as the possible therapeutic applications of TC in degenerative corneal disorders such as keratoconus.

Reappraising the microscopic anatomy of human testis: identification of telocyte networks in the peritubular and intertubular stromal space

“…Based on this assumption, we have taken advantage of both dual immunofluorescence staining and ultrastructural analyses to conclusively verify whether the CD34-positive testicular stromal cells could represent TCs. Indeed, we herein demonstrated the presence of TCs in the human testicular stromal space with the aid of that can presently be considered their most specific immunohistochemical marker combination, namely CD34/PDGFRα double immunofluorescence 6 , 7 , 16 , 17 , 37 , 46 , 52 – 54 . Furthermore, the combination of CD34 and CD31 immunostaining helped us to undoubtedly discriminate between TCs (CD34-positive/CD31-negative) and the endothelium (CD34-positive/CD31-positive) of blood vessels, and also emphasized the frequent perivascular location of TCs in the intertubular stroma.…”

“…3A,B ). We then characterized more in depth the immunophenotype of these testicular stromal cells by CD34/platelet-derived growth factor receptor α (PDGFRα) double immunofluorescence staining, a cell surface antigenic combination currently considered among the most reliable for the identification of TCs by light microscopy 6 , 7 , 16 , 17 , 37 , 46 , 52 – 54 . Such double immunolabeling showed coexpression of PDGFRα in all CD34-positive interstitial cells distributed in the outer layer of the peritubular tissue and in the intertubular stroma (Fig.…”

Ultrastructural and immunohistochemical characteristics of telocytes in human scalp tissue

“…In recent years, researchers have used focused ion beam scanning electron microscopy to investigate the 3D imaging of TCs in human dermis, and have revealed the existence of Tps with various conformations: (i) long, flattened irregular veils (ribbon-like segments) with knobs, corresponding to podoms, and (ii) tubular structures (podomers) with uneven calibre because of irregular dilations (knobs) -the podoms 10 . So far, TCs have been detected in many tissues and organs, including the heart 11,12 , lung 13,14 , skeletal muscle 15 , skin 16,17 , eye 18,19 , liver 20 , uterus 21 and urinary system 22,23 .…”

The Telocytes in the Subepicardial Niche

“…PDGFR-α was not tested in previous studies on epicardial and subepicardial TCs, although Creţoiu and Popescu indicated that 'CD34/PDGFR[-]α double immunohistochemistry can orientate the diagnosis' [55]. This double expression was used for TC identification in other normal and pathological non-cardiac tissues [56][57][58][59][60]. Cardiac TCs were indicated to have a CD34-positive/PDGFR-α-positive phenotype [61], but this resulted in cell cultures that did not use any sorting molecules; cells were sorted solely based on morphological criteria.…”