Hou Lab

1. Limbal stem cell deficiency

2. Ocular surface disease

3. Induced pluripotent stem cells 

4. Eye banking D

5. Donor corneal tissue processing 

6. Donor corneal tissue evaluation

Development of novel tissue-cellular products for treatment of limbal stem cell deficiency:

The primary translational focus of my laboratory is the development of novel tissue-cellular products for treatment of limbal stem cell deficiency (LSCD). LSCD is a blinding disease that is estimated to be responsible for 15-20% of all corneal blindness worldwide. LSCD occurs when limbal stem cells (LSCs) found on the ocular surface are depleted or become dysfunctional due to ocular surface insults, such as autoimmune diseases (Stevens Johnson Syndrome, mucus membrane pemphigoid), alkaline/chemical burns, congenital disorders of the ocular surface (congenital aniridia), and iatrogenic injury to the limbus (glaucoma procedures, pterygium surgery, medicamentosa). Loss of these cells results in inability to regenerate the clear corneal epithelium, resulting in corneal conjunctivalization, scarring, and ulceration. 

Despite the heavy global disease burden, effective therapies for LSCD are limited. One of the most promising emerging therapies for LSCD is cultivated limbal epithelial cell transplants (CLET). Donor LSCs cultured on human amniotic membrane have been shown to restore corneal transparency and maintain a population of healthy donor corneal epithelium in the short-term when transplanted onto an eye with LSCD. However, long-term survival of the donor cells after CLET has been limited and immunorejection remains a significant challenge.    

In order to address the first of these two issues, our lab is evaluating Descemet's membrane (DM) as a novel culture substrate, transplant carrier, and pseudoniche for donor LSCs. Stem cell function is heavily dependent on the extracellular environment, or stem cell niche. In CLET, LSCs are transplanted without a supporting niche. This results in the rapid terminal differentiation to mature corneal epithelium of the transplanted LSCs, limiting their long-term sustainability on the ocular surface. DM is a naturally occuring basement membrane (type IV) collagen, that is optically clear, resistant to collagenase digestion, and rich in proteins found in the limbal niche. These proteins (vitronectin, SPARC/BM40 are known to support the proliferation and stemness of stem cells in culture. Our lab is working on evaluating the niche-like potential of DM and developing DM-based therapies, like DM-based CLET grafts, for treatment of LSCD.     

In order to address the immunorejection issue of CLET, our lab is further working on the use of induced pluripotent stem cells (iPSC) to generate autologous LSCs for transplantation. Using iPSC technology, a patient's own autologous cells, such as skin fibroblasts, can be reprogrammed into iPSC and then differentiated into LSCs for transplantation. LSCs generated in this manner have no risk of rejection. The focus of our lab is on optimizing the differentiation of iPSC into LSC and evaluating the impact of different substrates, like DM, on the differentiation and maintanence of iPSC-derived LSCs.

Our lab is also piloting first-in-human clinical trials to evaluate the safety and efficacy of acellular DM transplants on the corneal surface for treatment of partial LSCD and other ocular surface diseases.

Optimization of Donor Corneal Tissue Processing and Evaluation: 

Corneal transplantation is the most common transplant done worldwide, with over 60,000 performed annually in the U.S. alone. With the advent of modern lamellar corneal transplantation (partial thickness transplants), donor tissue processing to isolate various lamella or cells of the cornea for targeted transplantation has grown in complexity. Our lab, in collaboration with the Lions Gift of Sight, is actively involved in pioneering novel tissue processing techniques for improving surgical outcomes with corneal transplantation. This includes the refinement of nomograms for cutting nanothin DSAEK, the introduction of hinged-DMEK to facillitate intraoperative unfolding, and the development of frictionless DMEK graft injectors to minimize graft injury during transplantation. 

Our lab is also involved in developing new tools for donor tissue evaluation of highly processed tissues. With the growing complexity of modern donor tissue processing prior to corneal transplantation, the potential for damage to the tissue is higher than ever. In order to rule-out tissues that are unsuitable for transplantation after processing, newer tools are needed. Our lab is active in development and validation of smart-image analysis software solutions for evaluation of tissue damage and donor tissue suitability. Our custom software is currently being used in clinical testing to establish clinical-relevant thresholds for donor tissue rule-in and rule-out.

Additionally, with the rise in number of graft injectors and graft delivery constructs on the market, more refined assays for validating the safety of these products in needed. Our lab has been a leader in development of novel, non-invasive, chemical assays to assess graft viability in pre-loaded DMEK injectors, which is a growing need in the field of eye banking.