The objective of this grant application is to train Dr. Charles Yu in the scientific skills and knowledge necessary for a career as an independent scientist translating scientific discoveries to clinically useful applications, specifically the restoration of vision in patients with corneal blindness. In additional to the primary goal of training Dr. Yu to become an independent investigator, this program may have a significant impact on the treatment of corneal blindness through the development of a new corneal replacement technology. Candidate Dr. Yu is a fellowship trained ophthalmologist specializing in corneal blindness and has a deep interest in developing new technologies to cure blindness. He is an expert in corneal innervation, developing artificial corneas and animal models of eye disease, ocular infections, and refractive surgery clinical trials. He has a strong background in the basic sciences having completed numerous research projects and a Howard Hughes Medical Institute sponsored medical research fellowship. He is currently an assistant professor and a K12 scholar at the University of Illinois Eye and Ear Infirmary. During this training period he will take numerous courses in engineering and materials science and complete two internships to develop his skill in polymer chemistry and industrial design. Environment The University of Illinois Eye and Ear Infirmary is one of the largest centers of vision research in the US, ranking top 4 in NIH funding in the last fiscal year. The department has a total of 47 full time faculty members, with 24 of them engaged in basic science or translational research. The research program encompasses the most critical areas of vision research, including investigations into the causes and pathology of blinding diseases, the development of innovative techniques and instruments for diagnosing and monitoring the progression of eye disease, genome-wide association studies of retinal diseases and visual functioning and retinal processes. The department commits over 22,000 square feet of its physical space to research. Research The cornea comprises the outer anterior layer of the eye. A normal cornea is transparent and curved, focusing light from the outside world. When injured by disease or dysfunction the cornea becomes opaque, causing scattering of light and loss of visual function. In cases where corneal stem cells have been damaged or there is vascularity, transplantation cannot be performed due to risk of rejection. Currently in these situations a Boston Keratoprosthesis Type I (BKpro) can be performed. The 5 year success rate varies from 50-70% depending on study. However BKpro remains limited by its technical difficulty and rate of complications such as extrusion, infection, and particularly membrane formation and glaucoma. These complications occur at a rate of up to 65% and 76%, respectively. There is a gap in the current understanding of why prosthetic membranes form and why there is often relentless membrane formation or glaucoma in these patients despite placement of pressure regulating glaucoma drainage devices. Also there is potential for design advances to reduce the complexity of surgical implantation and need for donor cornea tissue. This study proposes the development of a easy to implant minimally invasive keratoprosthesis (MiKpro) device, which can be implanted into the cornea through a 3 mm trephination without use of donor cornea tissue. This study offers the opportunity to both study the pathophysiology leading to keratoprosthesis complications and create a useful corneal replacement which can be implanted through a small wound and does not require donor corneal tissue.

Public Health Relevance

Therearetensofthousandsofpatientswhosufferfromcornealblindnessduetoaccidents,diseases, andgeneticcauses.ThisprojectwilltrainDr.Yutodevelopnewwaysofcombatingcornealblindness.It willalsocreateanewdevicewhichcanbeusedbysurgeonstoreplacedamagedcorneasandrestore visiontoblindpatients.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
7K08EY027459-03
Application #
9912320
Study Section
Special Emphasis Panel (ZEY1)
Program Officer
Agarwal, Neeraj
Project Start
2019-04-09
Project End
2021-05-31
Budget Start
2019-04-09
Budget End
2019-05-31
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305