We are seeking to understand the effects of inherited retinal disease upon brain structures normally dedicated to vision.

These studies are conducted both in human patients with identified inherited retinal disease, such as Leber's congenital amaurosis (LCA), as well as in animal models of the disease.

Ocular gene therapy approaches have been shown to restore function to the retina in animal models of LCA caused by mutations in the RPE65 gene. In recent work, we have shown that such treatment restores cortical responses to light in dogs born blind. Additionally, it appears that the anatomical structure of the visual pathway is relatively intact in human subjects with the RPE65 mutation and LCA.

To further this work we have begun studying the effect of congenital blindness from many causes upon the organization of visual cortex for cross-modal sensory processing and the relation of these responses to changes in structure and metabolic function.

Relevant Publications and Links:

• AV Cideciyan, TS Aleman, SG Jacobson, H Khanna, A Sumaroka, GK Aguirre, SB Schwartz, EA Windsor, S He, B Chang, EM Stone, A Swaroop. (2007, Nov). Centrosomal-ciliary gene CEP290/NPHP6 mutations result in blindness with unexpected sparing of photoreceptors and visual brain: implications for therapy of Leber congenital amaurosis. Hum Mutat, 28(11), 1074-83.

• GK Aguirre, MA Komáromy, AV Cideciyan, DH Brainard, TS Aleman, AJ Roman, BB Avants, JC Gee, M Korczykowski, WW Hauswirth, GM Acland, GD Aguirre, SG Jacobson. (2007, Jun). Visual Cortex Intact and Responsive Despite Early Retinal Blindness from RPE65 Mutation. PLOS-Medicine, 4(6), e230.

• A press release regarding the Canine and Human fMRI study is available

• A Neurology Today article describing the study :: View Article - PDF

• Additional information regarding the gene-therapy clinical trial for LCA from RPE65 mutations

This work is conducted in collaboration with the following groups:

	The Center for Hereditary Retinal Degenerations at the Scheie Eye Institute
	Dr. William Hauswirth of the University of Florida
	The Laboratories of Dr. Gustavo D. Aguirre and Andras M Komaromy at the University of Pennsylvania School of Veterinary Medicine
	Dr. Gregory Acland of the Baker Institute of Cornell University
	Dr. James Gee of the Penn Image Computing & Science Lab
	Dr. David Brainard of the Department of Psychology at the University of Pennsylvania

Damage to early visual cortical areas can produce impairments in visual perception. Most dramatic is the blindness that results from damage to striate regions. It has long been recognized, however, that residual visual abilities can persist perimetrically within blind fields.

Our studies examine both the alteration of visual representation in patients following cortical damage, as well as the organization of retinotopic visual areas in intact subjects.

Frequently, patients recover some amount of vision in the months following a visual cortex lesion. Behavioral and neuroimaging studies suggest that the spared hemisphere (the contralesional cortex) may be altered in this recovery process. To better study the role of contralesional cortex following a cortical lesion, we have begun to examine the representation of the ipsilateral visual field in normally sighted subjects.

Relevant Publications and Links:

• PD Radoeva, S Prasad, DH Brainard, GK Aguirre. (2008). Neural activity within area V1 reflects unconscious visual performance in a case of Blindsight. Journal of Cognitive Neuroscience, 20(11), 1927-1939.

• PD Radoeva, S Prasad, DH Brainard, GK Aguirre. (2007). |Representation of the Ipsilateral Visual Field in Early Retinotopic Cortex Vision Sciences Society Abstract. - 4.1MB PDF