This post will begin a series of entries relating to research in Penn’s Stellar-Chance Laboratories under the surveillance of Dr. Jean Bennett, M.D., Ph.D. I have been fortunate enough to acquire an internship in Dr. Bennett’s laboratory that has and will allow me to continue to observe and aid in both the clinical and laboratory research aspects of her clinical trials for gene treatment of inherited retinal degenerations.

Dr. Bennett is currently an FM Kirby Professor of Ophthalmology, having graduated from Yale with a BS in Honors Biology, A Ph.D. in Zoology from Berkeley, and an M.D. from Harvard Medical School. Her current, and most well-renowned, work consists of her research in the identification and characterization of genes that are defective in blinding and currently untreatable hereditary retinal degenerations such as retinitispigmentosa, macular degeneration and choroideremia. In order to gain better comprehension of the genetic disorders that initiate the development of such conditions, Dr. Bennett began with a study on the genetics behind inherited blindness in dogs. The dogs in the experiment lacked a specific protein that provides a nutrient that is essential for the retina to go through the electrical process that results in vision. The disease in humans is referred to as Leber Congenital Amaurosis (LCA), and often presents itself in humans by dramatically worsening vision over the host’s first twenty years of life. By age eighteen, host’s are typically considered to be legally blind. After successfully developing a gene therapy through a viral vector mechanism (in which the missing gene is surgically injected via a viral infection tothe host’s retina) that effectively cured the lab dogs of blindness, Dr. Bennett led her team to begin running clinical trials on humans, even children.

I was lucky enough to have the opportunity to meet Dr. Bennett’s first young patient, Corey Haas. Corey, who is currently eleven years old and has been seeing exponentially better in his left eye since his first injection with the viral vector two years ago, is currently at CHOP awaiting his second injection for his right eye. This past week, Corey underwent some retinal imaging with one of the most complex pieces of imaging machinery I have ever set my eyes on. UPenn is the home of one of four Adaptive Optics Scanning Laser Ophthalmoscopy Machines in existence (Pictured above). At 32 frames per second, this machine can take microscopic images of individual retinal cells (the rods and cones). The Camera itself operates on two focuses. Corey, or any patient, would put their head up on a level surface and stares at a target through a set of lenses, and during the first focusing process, the computer digitally adapts to any imperfections in Corey’s cornea such as those created by astigmatism. Then, a second focusing process begins to adjust for the axial length (the distance between Corey’s fovea and cornea) so as to get the clearest image of his retina. The target that Corey looks at can be moved around so that different parts of the retina can be photographed. Images show data relating cone density, and can be read along with fMRI images to determine high areas of cone activity. Cone photoreceptors display as white dots on the black canvas of the retina as shown in the image below:

While LGA is a relatively rare condition, only occurring in 1 out of every 50,000 newborns according to the US National Library of Medicine, http://ghr.nlm.nih.gov/condition/leber-congenital-amaurosis, the dramatic progress that Corey and his fellow patients are making under the care of Dr. Bennett and her team may expedite development of gene therapy for more common retinal diseases, such as age-related macular degeneration.

Watch Corey’s Story Below!
http://www.youtube.com/watch?v=Z-VY64rSYr0