Tear film and dry eye
Tears, secreted from lacrimal gland, meibomian gland and other orbital subsidiary glands, form the tear film on the ocular surface to provide nutrition, lubrication and protection of corneal and conjunctival epithelium cells. The damage of tear film can result in ocular surface inflammation, apoptosis of epithelial cells, squamous metaplasia, goblet cell loss, and other pathologic changes of the ocular surface, which causes various symptoms in patients. In the severe cases, abnormality of tear film can cause corneal ulcer, neovascularization, as well as permanent visual impairment.
The prevalence of dry eye is very high in the nation and the world. About 20-30% of Chinese population is affected by dry eye. Prof Liu’s group has been committed to the research of dry eye epidemiology, pathogenesis, animal models, drug screening, and treatments with research funding from national and local governments. Meanwhile, the clinical center of the eye institute, Xiamen Eye Center, participated and played key roles in many multi-center clinical researches. They are the first in the world to establish a tissue culture model to mimic the pathological changes of dry eye,they also established the stable mice dry eye model by BAC induction. They have published a series of high-rank papers on international and national ophthalmologic journals, and filed several Chinese patents in the field of dry eye research.
Corneal tissue engineering
According to the statistics, more than 4 million people in China are blinded because of severe corneal diseases. However, only about 3,000 cases of corneal transplantation were performed each year in China due to the extreme shortage of cornea donor tissue. Therefore, the development and application of corneal tissue substitutes, so-called tissue engineered cornea, is worth of persistent and industrious investigation.
Prof Liu’s research team is committed to corneal tissue engineering study, including the tissue engineered corneal epithelium, xenogenic tissue engineered corneal stroma, and tissue engineered corneal endothelial. The research projects are supported by the National High Technology Research and Development Program (863 Program) and the Natural Science Foundation of China. In the past three years, they have made major progress in the optimization of tissue engineered corneal epithelium, cell extraction and effectiveness evaluations of xenogenic engineered corneal stroma. In Science supplement issue in April 2012, they reported that lamellar corneal tissue from porcine was successfully transplanted to human, which is the first report of xenogenic corneal lamellar keratoplasty in human.
Corneal epithelial stem cell
Corneal epithelial stem cell, the only origination of the corneal epithelial cells, plays a pivotal role in maintaining the stability of corneal epithelium and transparency of corneal tissue. Severe corneal epithelial stem cell deficiency can cause visual impairment and blindness. Our group has been focusing on the proliferation and differentiation of corneal epithelial stem cell, limbal stem cell niche, ex vivo expansion and transplantation of limbal stem cell. We established mouse and rabbit models of corneal epithelial stem cell deficiency, modified ex vivo expansion protocol, unveiled the effect of hypoxia on the proliferation and differentiation of limbal stem cell. Moreover, we developed new limbal stem cell transplantation techniques and we are now applying these techniques in the treatment of limbal stem cell deficiency.
Amniotic membrane related tissue engineering
Amniotic membrane has been widely applied in ophthalmology and other tissue engineering areas in the past 10 years due to its special biological properties and weak immunogenicity. In ophthalmology, amniotic membrane is mainly used in the treatment of ocular surface diseases. A large number of clinical studies have shown that amniotic membrane is meditative in anti-inflammation, anti-scarring, anti-angiogenesis, as well as the promotion of the ocular surface epithelial wound healing. Our team has a strong background in amniotic membrane research. Previously, we have investigated the therapeutic mechanism of amniotic membrane in the treatment of ocular surface diseases at molecular and cellular levels. We are now interested in new applications of amniotic membrane in different medical science areas, and the development of new tissue engineered products related to amniotic membrane.
Squamous Metaplasia of the Ocular Surface Epithelium
Squamous metaplasia of the ocular surface epithelium is frequently present in various ocular surface diseases such as dry eye, Stevens-Johnson syndrome, cicatricial pemphigoid, pterygium and pinguecula. Our team has set up a squamous metaplasia tissue culture model using air-liquid interface culture of corneal limbus or conjunctival tissue, and found that p38 MAPK and Wnt signaling pathway is involved in the pathogenesis of squamous metaplasia. We also found down-regulation or silence of pax6 gene is associated with abnormal epidermal differentiation of the ocular surface epithelium. We further found that application of p38 MAPK inhibitor, re-introducing of pax6 gene, co-culture with amniotic membrane, application of amniotic membrane extract, and low oxygen tension culture environment can inhibit or reverse squamous metaplasia of ocular surface epithelium to a certain degree in ex vivo tissue culture model. We now have great interest in the clinic treatment of squamous metaplasia based on our new knowledge on this pathological process.