Katherine Mancuso
Medical College of Wisconsin
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Publication
Featured researches published by Katherine Mancuso.
Nature | 2009
Katherine Mancuso; William W. Hauswirth; Qiuhong Li; Thomas B. Connor; James A. Kuchenbecker; Matthew C. Mauck; Jay Neitz; Maureen Neitz
Red–green colour blindness, which results from the absence of either the long- (L) or the middle- (M) wavelength-sensitive visual photopigments, is the most common single locus genetic disorder. Here we explore the possibility of curing colour blindness using gene therapy in experiments on adult monkeys that had been colour blind since birth. A third type of cone pigment was added to dichromatic retinas, providing the receptoral basis for trichromatic colour vision. This opened a new avenue to explore the requirements for establishing the neural circuits for a new dimension of colour sensation. Classic visual deprivation experiments have led to the expectation that neural connections established during development would not appropriately process an input that was not present from birth. Therefore, it was believed that the treatment of congenital vision disorders would be ineffective unless administered to the very young. However, here we show that the addition of a third opsin in adult red–green colour-deficient primates was sufficient to produce trichromatic colour vision behaviour. Thus, trichromacy can arise from a single addition of a third cone class and it does not require an early developmental process. This provides a positive outlook for the potential of gene therapy to cure adult vision disorders.
The Journal of Neuroscience | 2010
Bevil R. Conway; Soumya Chatterjee; Greg D. Field; Gregory D. Horwitz; Elizabeth N. Johnson; Kowa Koida; Katherine Mancuso
Color has become a premier model system for understanding how information is processed by neural circuits, and for investigating the relationships among genes, neural circuits, and perception. Both the physical stimulus for color and the perceptual output experienced as color are quite well characterized, but the neural mechanisms that underlie the transformation from stimulus to perception are incompletely understood. The past several years have seen important scientific and technical advances that are changing our understanding of these mechanisms. Here, and in the accompanying minisymposium, we review the latest findings and hypotheses regarding color computations in the retina, primary visual cortex, and higher-order visual areas, focusing on non-human primates, a model of human color vision.
Journal of The Optical Society of America A-optics Image Science and Vision | 2007
Katherine Mancuso; Anita E. Hendrickson; Thomas B. Connor; Matthew C. Mauck; James J. Kinsella; William W. Hauswirth; Jay Neitz; Maureen Neitz
Recombinant adeno-associated virus (rAAV) is a promising vector for gene therapy of photoreceptor-based diseases. Previous studies have demonstrated that rAAV serotypes 2 and 5 can transduce both rod and cone photoreceptors in rodents and dogs, and it can target rods, but not cones in primates. Here we report that using a human cone-specific enhancer and promoter to regulate expression of a green fluorescent protein (GFP) reporter gene in an rAAV-5 vector successfully targeted expression of the reporter gene to primate cones, and the time course of GFP expression was able to be monitored in a living animal using the RetCam II digital imaging system.
Visual Neuroscience | 2008
Matthew C. Mauck; Katherine Mancuso; James A. Kuchenbecker; Thomas B. Connor; William W. Hauswirth; Jay Neitz; Maureen Neitz
Delivery of foreign opsin genes to cone photoreceptors using recombinant adeno-associated virus (rAAV) is a potential tool for studying the basic mechanisms underlying cone based vision and for treating vision disorders. We used an in vivo retinal imaging system to monitor, over time, expression of virally-delivered genes targeted to cone photoreceptors in the Mongolian gerbil (Meriones unguiculatus). Gerbils have a well-developed photopic visual system, with 11-14% of their photoreceptors being cones. We used replication deficient serotype 5 rAAV to deliver a gene for green fluorescent protein (GFP). In an effort to direct expression of the gene specifically to either S or M cones, the transgene was under the control of either the human X-chromosome opsin gene regulatory elements, i.e., an enhancer termed the locus control region (LCR) and L promoter, or the human S-opsin promoter. Longitudinal fluorescence images reveal that gene expression is first detectable about 14 days post-injection, reaches a peak after about 3 months, and is observed more than a year post-injection if the initial viral concentration is sufficiently high. The regulatory elements are able to direct expression to a subpopulation of cones while excluding expression in rods and non-photoreceptor retinal cells. When the same viral constructs are used to deliver a human long-wavelength opsin gene to gerbil cones, stimulation of the introduced human photopigment with long-wavelength light produces robust cone responses.
Visual Neuroscience | 2008
John L. Barbur; Marisa Rodriguez-Carmona; J.A. Harlow; Katherine Mancuso; Jay Neitz; Maureen Neitz
Visual Neuroscience | 2006
Katherine Mancuso; Maureen Neitz; Jay Neitz
Advances in Experimental Medicine and Biology | 2010
Katherine Mancuso; Matthew C. Mauck; James A. Kuchenbecker; Maureen Neitz; Jay Neitz
Journal of Vision | 2010
Matt Mauck; Julie Garcia; Katherine Mancuso; James A. Kuchenbecker; Andy Salzwedel; Maureen Neitz; Jay Neitz
Journal of Vision | 2010
Katherine Mancuso; Jay Neitz; William W. Hauswirth; Thomas B. Connor; Maureen Neitz
Investigative Ophthalmology & Visual Science | 2008
Katherine Mancuso; Maureen Neitz; William W. Hauswirth; Q. Li; Thomas B. Connor; J. Kuchenbecker; Matthew C. Mauck; Jay Neitz