Therese Cronin, PhD

University of Pennsylvania - Visionary

Project Title: "Restoring function to degenerated retinas by gene therapy using virally encoded light-responsive molecules"

 

Blindness frequently results from degeneration and disease of the light-sensitive tissue at the back of the eye called the retina.  This is true for the spectrum of pathologies classed as Retinitis Pigmentosa as well as for Age-Related Macular Degeneration. Many retinal therapies focus on preventing or stemming the progression of these blinding diseases.  There are fewer options available to restore sight to patients for whom the symptoms are advanced and significant loss of vision has already occurred.  This project is therefore concerned with the therapeutic use of light-sensing proteins adapted for the retina.  These molecules are of increasing interest as part of the field of optokinetic technologies. Significant international research efforts have gone into engineering such proteins so that they may restore light sensitivity to the remaining cells in the degenerated retina.  The efficient delivery of these “molecular prosthetics” is now necessary in order to test their efficacy in vivo; however retinal delivery has proven a major bottleneck to the project.  Our goal is to overcome this obstacle by the development of retinal targeted viral delivery tools.

Testing viral-mediated transfer of light-sensitive genes to the inner retina of non-human primates will be the first step in developing a viable treatment strategy that could be applied to humans with end-stage retinal degeneration. Given the current state of the art in retinal gene transfer, which has so far been found to be safe and efficacious in at least 18 patients, it is timely to explore the options for gene-based restoration of visual function in cases of advanced blindness. 

We anticipate that by overcoming the obstacle of targeted delivery to intermediate cell layers of the retina, we can accelerate the effort to bring these optokinetic molecules such as Channelrhodopsin-2 to the point of clinical testing.