Dry eye disease (DED) is a multifactorial disease characterized by a disrupted tear film homeostasis and inflammation leading to visual impairments and pain in patients. Aqueous-deficient dry eye (ADDE) causes the most severe progressions and depends mainly on the loss of functional lacrimal gland (LG) tissue. Despite a high prevalence, therapies remain palliative. Therefore, it is of great interest to develop new approaches to curatively treat ADDE. Mesenchymal stem/stromal cells (MSC) have been shown to induce tissue regeneration and cease inflammation. Moreover, an increasing amount of MSC was found in the regenerating LG of mice. Therefore, this study investigated the therapeutic effect of MSC transplantation on damaged LGs using duct ligation induced ADDE in mice. Due to the transplantation of sex-mismatched and eGFP-expressing MSC, MSC could be identified and detected until day 21. MSC transplantation significantly improved LG regeneration, as the amount of vital acinar structures was significantly increased above the intrinsic regeneration capacity of control. Additionally, MSC transplantation modulated the immune reaction as macrophage infiltration was delayed and TNFα expression decreased, accompanied by an increased IL-6 expression. Thus, the application of MSC appears to be a promising therapeutic approach to induce LG regeneration in patients suffering from severe DED/ADDE.

When an eye has become irreversibly blind or painful it is removed by enucleation or evisceration. The resulting anophthalmic socket usually receives a volume replacing implant and is subsequently fitted with a prosthetic shell for adequate cosmesis. Trauma, tumour or immunological pathomechanisms can result in loss of bone, orbital soft tissue volume, conjunctival contraction or implant exposure and make wearing a prosthesis impossible. In this situation as well as in numerous diseases limited to the conjunctiva (e.g. Pterygium, or cicatrizing conjunctivitis) strategies to substitute the lost tissue are required. This review describes the established and proposed surgical techniques, substitute tissues and materials to restore adequate conjunctival lining or orbital volume.

The long-term success of visual rehabilitation in patients with severe conjunctival scarring is reliant on the reconstruction of the conjunctiva with a suitable substitute. The purpose of this study is the development and investigation of a re-epithelialized conjunctival substitute based on porcine decellularized conjunctiva (PDC). PDC was re-epithelialized either with pre-expanded human conjunctival epithelial cells (PDC + HCEC) or with a human conjunctival explant placed directly on PDC (PDC + HCEx). Histology and immunohistochemistry were performed to evaluate epithelial thickness, proliferation (Ki67), apoptosis (Caspase 3), goblet cells (MUC5AC), and progenitor cells (CK15, ΔNp63, ABCG2). The superior construct (PDC + HCEx) was transplanted into a conjunctival defect of a rabbit (n = 6). Lissamine green staining verified the epithelialization in vivo. Orbital tissue was exenterated on day 10 and processed for histological and immunohistochemical analysis to examine the engrafted PDC + HCEx. A human-specific antibody was used to detect the transplanted cells. From day-14 in vitro onward, a significantly thicker epithelium and greater number of cells expressing Ki67, CK15, ΔNp63, and ABCG2 were noted for PDC + HCEx versus PDC + HCEC. MUC5AC-positive cells were found only in PDC + HCEx. The PDC + HCEx-grafted rabbit conjunctivas were lissamine-negative during the evaluation period, indicating epithelial integrity. Engrafted PDC + HCEx showed preserved progenitor cell properties and an increased number of goblet cells comparable to those of native conjunctiva. Placing and culturing a human conjunctival explant directly on PDC (PDC + HCEx) enables the generation of a stable, stratified, goblet cell-rich construct that could provide a promising alternative conjunctival substitute for patients with extensive conjunctival stem and goblet cell loss.

Conjunctival repair is a crucial part of ocular surface reconstruction. Due to limitations of currently used substitute tissues, there is a need for the development of new scaffolds of consistent quality for conjunctival reconstruction. This study explored the biocompatibility and surgical usability of plastic-compressed collagen (PCC) as an alternative conjunctival substitute. PCC gels were produced by polymerization of collagen type I followed by plastic compression. Conjunctival defects were trepanned in rabbits and grafted using PCC or human amniotic membrane (AM) or remained ungrafted. Number of sutures, defect size, conjunctival hyperemia, and fornix depth were assessed at day 0, 3, 10, 14, and 28. Granulocytic infiltration, epithelialization, goblet cell count, and collagen fiber alignment were examined histologically at day 10 or 28. Suture loss, defect size, hyperemia, and fornix depth of the PCC group were not significantly altered compared with AM. Histologically, granulocytic infiltration revealed mild inflammation at day 10, but did not differ between the PCC and AM group at day 10 or 28. PCC was well integrated into the recipient conjunctiva with partial epithelialization after 10 days. After 28 days, all groups revealed a closed, multilayered epithelium with equal amount of goblet cells and randomly aligned stromal collagen fibers and no indication for conjunctival scarring. In summary, PCC gels offer a good surgical applicability and ocular surface biocompatibility with minor host reaction and no evidence of consecutive conjunctival scarring. Impact Statement: Conjunctival integrity is crucial for a healthy ocular surface and visual acuity. In severe cases of inflammatory surface disorders or after trauma, thermal or chemical burns as well as after ocular surgery, a surgical reconstruction using conjunctival substitutes is required. Due to limitations of currently used substitutes, such as the amniotic membrane, there is a need for the development of new scaffolds of consistent quality for conjunctival reconstruction. This study explored the biocompatibility and surgical usability of plastic-compressed collagen as an alternative conjunctival substitute in a rabbit model.