The overall goal of our research is to determine and understand the genes and the molecular mechanisms that will lead to a broad overview and understanding of corneal transparency and wound healing in inherited corneal disorders of the anterior stroma and Bowman's membrane complex. Once the disease-causing gene(s) for Thiel-Behnke corneal dystrophy (CDB2) are cloned and characterized, this research will shed light on the associated mechanisms of wound healing and scarring, the most common cause for loss of vision necessitating in corneal transplantation. Genetic defects in the cornea in humans can result in serious loss of visual function with accompanying symptoms of severe pain, tearing and photophobia. Given the relatively large number of affected individuals, it is imperative that the inheritable corneal diseases become the focus of intense study and their treatments become a high priority. Beta-ig-h3, the causative gene for Reis-Bucklers' corneal dystrophy (CDB1), and the yet to be identified causative gene for ThieI-Behnke (CDB2) may play a crucial role in corneal transparency via its structural role in the extracellular matrix of the cornea. The similar clinical phenotypes of the two diseases may suggest that the CDB2 gene also plays a vital role in wound healing and scarring of the Bowman's membrane complex. Long term goals will include engineering transgenic animals that express mutant proteins will enhance our understanding of developmental mechanisms and functions of the cornea at the molecular level. This will be accomplished by elucidating the promoter and enhancer elements of the disease-causing gene through the expression of mutant forms and assessment on the phenotypic impact in the cornea. As the causative gene(s) are characterized through these transgenic models, it should be possible to design specialized therapies based on knowledge of the underlying biochemical, structural and metabolic defect. Eventually, this information should also be of use in determining the genetic cause of these diseases in other patients and will contribute, ultimately, to more accurate diagnosis, effective genetic counseling, and better regimens for prevention and/or treatment.
| Nakamura, Hisashi; Li, Frank T; Foltermann, Miles O et al. (2012) Individual phenotypic variances in a family with Thiel-Behnke corneal dystrophy. Cornea 31:1217-22 |
| Zhao, Xinping C; Nakamura, Hisashi; Subramanyam, Sumitra et al. (2007) Spontaneous and inheritable R555Q mutation in the TGFBI/BIGH3 gene in two unrelated families exhibiting Bowman's layer corneal dystrophy. Ophthalmology 114:e39-46 |
| Yoshikawa, Shunichi; Norcom, Evan; Nakamura, Hisashi et al. (2007) Transgenic analysis of the anterior eye-specific enhancers of the zebrafish gelsolin-like 1 (gsnl1) gene. Dev Dyn 236:1929-38 |
| Zhao, Xinping C; Yee, Richard W; Norcom, Evan et al. (2006) The zebrafish cornea: structure and development. Invest Ophthalmol Vis Sci 47:4341-8 |
