Novel biomaterials and photocages with anti-viral activity for transplantation

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RATIONALE AND BACKGROUND: Herpes simplex virus (HSV) infections in the cornea has an incidenceof up to 500,000 cases each year in the US alone. Once infected, the virus becomes latent and remains withinthe cornea and nerves. When reactivated (by a range of triggers including certains foods, sunlight, surgery), thepatient will have recurrences of the disease. The disease leads to ulceration of the corneal surface to deeperullcerations, loss of nerve sensitivity leading to scarring and corneal blindness or even corneal perforation.Patients are treated with systemic anti-viral drugs but corneal transplantation is the treatment of choice torestore vision, even though the prognosis is extremely poor - 22% success over 5 years. The poor prognosis isdue to the HSV latency and reactivation. An effective treatment is therefore needed.OBJECTIVE: Our objective therefore is to develop an effective treatment, using tissue engineering andphotochemistry approaches.PROPOSED RESEARCH:We will combine our previous success in developing artificial corneas that have allowed corneal cell and nerveregeneration when implanted into pigs with new ways to delivery anti-viral drugs such as acyclovir. Novelphotocages will be developed for precise, controlled release of acyclovir, and incorporated into cornealimplants to release the drug during surgery to prevent HSV reactivation.We will also be testing the efficacy ofanti-viral peptides, e.g. LL-37, in combating primary HSV infection and/or preventing viral reactivation.EXPECTED SIGNIFICANCEOur results could become a means by which drugs can be delivered to the eye (not just the cornea) and releasedbio-photonically. This would allow for high risk corneal transplants and transplants to the retina and otherinternal parts of the eye where drugs or growth factors need to be delivered and activated over time, without theuse of invasive techniques like injection.