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• Goblet cells - sine qua non for conjunctival rehabilitation
  Sara I. Van Acker, Sorcha Ní Dhubhghaill
  Published on: 18 February 2022

• Published on: 18 February 2022

  Goblet cells - sine qua non for conjunctival rehabilitation

  • Sara I. Van Acker, PhD student Antwerp Research Group for Ocular Science (ARGOS), Translational Neurosciences, Faculty of Medicine, University of Antwerp
  • Other Contributors:
    • Sorcha Ní Dhubhghaill, Consultant corneal and cataract Surgeon

  To the editor,

  We read with interest the recent publication by Bertolin et al. (“In vitro establishment, validation and characterisation of conjunctival epithelium outgrowth using tissue fragments and amniotic membrane”). Their validated conjunctival analogue of the simple limbal epithelial transplantation does represent a promising advance in the field. It is, however, interesting to note that the established tissue application was mainly validated on its growth potential and not specifically on its ability to reinstate a healthy ocular mucosal surface.

  Functional validation is of utmost importance, especially as the glued fragments are directly transplanted. This approach circumvents the need for expensive cell culture but also bypasses the stringent release criteria for cell therapies or tissue-engineered transplantation products. We would suggest that before this technique can be considered fully validated, it should be demonstrated that the obtained conjunctival cells contribute to the first line of mucosal defence, i.e. barrier formation. Several conjunctival barriers can be identified, such as intercellular junction complexes, glycocalyx and secreted mucins. Bertolin et al. demonstrated the presence of tight junctions (cfr. ZO-1 protein) and a glycocalyx (cfr. membrane-associated mucin-1), but failed to address the presence of goblet cells. As goblet cells are responsible for the secretion of mucin 5AC, which is the most abundant mucin in the mucin la...

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  To the editor,

  We read with interest the recent publication by Bertolin et al. (“In vitro establishment, validation and characterisation of conjunctival epithelium outgrowth using tissue fragments and amniotic membrane”). Their validated conjunctival analogue of the simple limbal epithelial transplantation does represent a promising advance in the field. It is, however, interesting to note that the established tissue application was mainly validated on its growth potential and not specifically on its ability to reinstate a healthy ocular mucosal surface.

  Functional validation is of utmost importance, especially as the glued fragments are directly transplanted. This approach circumvents the need for expensive cell culture but also bypasses the stringent release criteria for cell therapies or tissue-engineered transplantation products. We would suggest that before this technique can be considered fully validated, it should be demonstrated that the obtained conjunctival cells contribute to the first line of mucosal defence, i.e. barrier formation. Several conjunctival barriers can be identified, such as intercellular junction complexes, glycocalyx and secreted mucins. Bertolin et al. demonstrated the presence of tight junctions (cfr. ZO-1 protein) and a glycocalyx (cfr. membrane-associated mucin-1), but failed to address the presence of goblet cells. As goblet cells are responsible for the secretion of mucin 5AC, which is the most abundant mucin in the mucin layer of the tear film, its presence is crucial to obtain a normal, hydrated ocular surface. Presence of mucin-producing goblet cells is so characteristic of the conjunctiva that it is a cardinal feature of impression cytology techniques in the diagnosis of corneal limbal stem cell deficiency. We therefore consider goblet cells (and their associated mucin production) in 2D and 3D cultures the “sine qua non” for conjunctival epithelium and propose that it should be a core element of the validated characterization process.

  As functional goblet cells are difficult to maintain in culture, it could be debated that the absence of goblet cells in the outgrowth does not implicate their absence during in vivo expansion. If conjunctival stem cells in the outgrowth could be shown to have bipotent properties, it is reasonable to assume that conjunctival goblet cells can differentiate from these bipotent stem cells and that they can be preserved once they are placed in their natural tightly regulated environment, including the conjunctival innervation of the epithelium. Do the authors have any experience with goblet cell maturation? In any case, these properties would have to be well proven before this technique can be relied on in the clinic.

  Regards,
  Sara I. Van Acker
  Sorcha Ní Dhubhghaill

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  Conflict of Interest:
  None declared.

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