Human cornea is comprised of five layers: epithelium, Bowman’s layer, stroma, Descemet’s membrane, and endothelium, among which two layers (Bowman’s layer and Descemet’s membrane) are acellular and three layers contain cells with distinctive functions. Our lab has specific focuses on these different types of cells.

Corneal epithelium is under constant renewal throughout life, supported by stem cells locating at the peripheral limbal region of cornea, known as limbal stem cells (LSCs). Limbal stem cell deficiency (LSCD) is the leading cause of corneal blindness worldwide and cannot be treated by traditional corneal transplant. Current therapeutic options for LSCD include transplantation of LSCs using autograft or allograft. LSCs could be expanded in vitro prior transplantation, which requires less cells from donor eyes thus causing less damage in the healthy eye in autograft or enables LSC bank in allograft to benefit more patients and reduce cost. However, currently there is no specific marker available to distinguish LSCs from limbal progenitor cells, which are the daughter cells during differentiation and do not support a long-term regeneration. The lack of LSC marker causes a bottle neck to improve the current therapy for LSCD due to the lack of quality control on expanded LSCs. We have identified putative LSC groups and their daughter progenitor cell groups using transgenic mice and single-cell RNA sequencing. Their characteristic markers are currently under study as potential LSC markers and progenitor cell markers.

External damage to epithelium usually will not lead to scar formation. However, once the damage reaches corneal stroma, a scar will form. We found a list of small molecules secreted by corneal stromal cells after wounding when the scar started to disappear. Some of the listed molecules have been patented or proven by previous publications to facilitate would healing without a scar in other organs (e.g. skin). Whether these molecules can facilitate the corneal wound healing without a scar is under study using our wound-healing mouse model.

Corneal endothelium keeps cornea dehydrated to maintain its transparency. It is composed of a single layer of corneal endothelial cells with a predominately hexagonal shape. Although several publications report the heterogeneity of corneal endothelial cells, they are usually treated as a homogeneous cell population in clinics and in research. We observed the heterogeneity in our transgenic mice, which is related to the aging process. Whether the heterogeneity can be extended to human and to human-related diseases is under investigation.

In addition, we are trying to establish a new research model which is to culture a whole eye globe in vitro. This model is a useful tool to study cells and drug effect at an organ level, in addition to the existing cell level and animal level. We expect that this model will greatly facilitate the progress and reduce the cost of eye research and drug development once established.