Reconstruction and Regeneration of Corneal Endothelium: A Review on Current Methods and Future Aspects

Human cornea is a highly organized transparent tissue and is well determined by its functional layers as shown in (Figure 1). The posterior layer of the cornea is the endothelium which is a physiologically important monolayer of cells. Human Corneal Endothelium (CE) plays a major role in maintaining the corneal transparency, thickness and hydration [1,2]. As CE dysfunction is the second leading cause of corneal blindness and the human Corneal Endothelial Cells (CECs) are non-regenerative, its preservation and maintenance becomes a critical issue. The CECs have a low tendency to proliferate in vivo, as they are arrested in the G1 phase, and therefore these cells spread out to replace the deceased cells, thus maintaining the functional integrity and corneal deturgescence [3,4]. Accidental or surgical trauma can result into acute corneal endothelial dysfunction which results in the inability of the pumping function of the endothelium which is necessary for the drainage of excess fluids. This causes critical anomalies like stromal edema, loss of transparency and most importantly the visual acuity which usually leads to the clinical condition of bullous keratopathy [2]. The corneal endothelium is assumed to be originated from the neural crest cells. It has already been described that the neural crest cells migrate and differentiate during the developmental phases of the cornea. Periocular mesenchymal cells are originated from the neural crest cells and are responsible for the development of the corneal epithelium and the synthesis of the primary stroma. These cells further migrate to the periphery of the optic cup eventually moving between the lens and the corneal epithelium for the development of the trabecular meshwork and the corneal endothelium. Further, in the second phase of the development, the neural crest cells occupy the primary stroma and differentiate into corneal keratocytes [5]. CECs are metabolically active and continuously functions as a fluid pump for the movement of fluid from the stroma and the anterior chamber. Thus, as described earlier, the endothelial layer plays a significant role, but lacks the capacity to regenerate and hence its viability should be maintained. Currently, surgical replacement of the diseased endothelium by a healthy donor’s tissue using corneal transplantation is the only solution to restore vision [6]. However, the availability and quality of corneas are main concerns; more than 40% of the donated corneas to the Veneto Eye Bank Foundation (FBOV – Venice, Italy) are rendered unsuitable for transplantation. Additionally, more than 60% of the donors are over 60 years old which may lead to graft rejection in the preliminary phases of evaluation due to low endothelial cell density.