Regenerative Medicine in Vision Research

At the UPMC Eye Center, much of the research focuses on regenerative medicine, a field that started with restoration of heart tissue in the 1990s and has since included research into the use of stem cell therapy in vision restoration. The Louis J. Fox Center for Vision Restoration of UPMC and the University of Pittsburgh is studying what can be done to treat the most common diseases associated with vision loss, including macular degeneration, diabetic retinopathy, and corneal scarring.

“There is a lot of exciting things going on in our research, and lot of it is related to regenerative medicine. In the past, once a tissue was damaged, it was assumed the game was over. That’s no longer the case,” said McGowan Institute for Regenerative Medicine affiliated faculty member Robert Hendricks, PhD, the Joseph F. Novak professor and vice chair for research, Departments of Ophthalmology, Molecular Genetics, and Biochemistry and Immunology, and director, Ophthalmology and Visual Sciences Research Center, University of Pittsburgh School of Medicine.

Under the direction of Dr. Hendricks, the Ocular Immunology Laboratory focuses on immunity to viral infections of the eye. Of particular interest is a complex disease called herpes keratitis, the leading infectious cause of blindness in the United States. The disease results from infection of the cornea by Herpes Simplex Virus (HSV), a virus that also causes cold sores, venereal disease, and potentially lethal encephalitis.

Like other HSV infections (cold sores, genital lesions) patients experience recurrent episodes of herpes keratitis. Each infection results in inflammation in the cornea and scar tissue formation. Accumulation of scar tissue causes progressive visual loss and ultimately corneal blindness. Dr. Hendricks’ laboratory focuses on three important issues:

Prevention of herpes keratitis: Up to 90% of us have been infected by HSV-1 and harbor the virus in a latent (quiescent) state in our sensory neurons, but in most of us the virus remains in a life-long quiescent state. In some people it periodically becomes active and causes disease. The Ocular Immunology Lab was first to demonstrate that a white blood cell called a CD8+ T cell attaches to latently infected neurons and maintains HSV in a quiescent state. The laboratory is exploring new approaches to augment the capacity of these CD8+ T cells to prevent recurrent herpes keratitis.

Treatment of herpes keratitis: Inflammation is a protective immune response, but when not properly controlled can damage tissue. The Ocular Immunology Lab is using state-of-the-art molecular and cellular approaches to understand the mechanisms of inflammation in eyes with herpes keratitis, with the goal of developing new and more efficient therapy to prevent progressive corneal scarring and visual impairment.

Replacement of scarred corneas: When corneas become badly scarred by recurrent herpes keratitis, the only approach to restore vision is to transplant a clear donor cornea. Unfortunately corneal transplants to eyes with herpes keratitis have a very high rate of rejection. In collaboration with a group from Aberdeen Scotland, the Ocular Immunology Lab is studying the cause of the enhanced rejection of corneal transplants in eyes with a history of herpes keratitis. Preliminary findings point to exciting new approaches to reduce the risk of transplant rejection in these patients.

Illustration: The Louis J. Fox Center for Vision Restoration of UPMC and the University of Pittsburgh.