2012 Group Project 5
The development of the eye occurs with the optic placode at a Carnegie stage 12 embryo (week 4). During this time any malfunction of development will create an abnormality of the eye. Abnormalities in vision can be acquired by environmental means, like that of Fetal Alcohol Syndrome or by Genetics such as the abnormalities discussed below. The purpose of this page is the give a brief overview of the development of the eye and some of the abnormalities which can occur.
Normal Eye Development
The normal early development of the eye begins with the optic primodium and sulcus developing in the neural folds at Carnegie stage 10 or around 22 days.
Leber Congenital Amaurosis
Leber Congenital Amaurosis (LCA) is an inherited retinal degenerative disorder that causes blindness or loss of sight at birth. LCA has a recessive pattern of inheritance where there is a 25% chance for a child to contract LCA.
LCA was first recognized by Dr Theodor Leber in 1869. He published the paper Ueber Retinitis pigmentosa und angeborene Amaurosa (About Retinitis pigmentosa and congenital Amaurosa) in Archiv fur Ophthalmologie (now known as Graefes Archive of clinical and experimental ophthalmology).
From 1869-2009, the major contributers to LCA research: "Courtesy: National Eye Institute, National Institutes of Health (NEI/NIH)."
- 1869- Dr. Theodor Leber (1840-1917), German ophthalmologist, first describes what is now known as Leber congenital amaurosis, an inherited retinal disease that causes severe visual impairment early in childhood 
- 1932-34- George Wald, Ph.D. first identified vitamin A in the retina during a National Research Council fellowship in biology 
- 1965- Human adeno-associated virus (AAV) was discovered.
- 1984- Drs. Nicolas Muzyczka and Paul Hermonat publish an article on adeno-associated virus (AAV) expresses that it can be used to introduce foreign DNA into human and murine tissue culture cells.
- 1990- Dr. T. Michael Redmond of the NEI's Laboratory of Retinal Cell and Molecular Biology, Section on Gene Regulation began work on RPE-specific monoclonal antibody.
- 1993- Dr. T. Michael Redmond of the NEI's Laboratory, cloned RPE65, a protein necessary for processing vitamin A in the visual cycle.
- 1997- RPE65 gene mutations identified as the cause of congenital blindness in some children with Leber congenital amaurosis.
- 1998- Dr. T. Michael Redmond's team in the NEI's Laboratory use the knockout mouse model to establish RPE65’s role in vitamin A metabolism. RPE65 gene mutation was discovered as causing congenital blindness in Briard dogs.
- 2001- Gene transfer RPE65 therapy used to restore vision in a Briard Dog by researchers at the University of Pennsylvania and University of Florida supported by the NEI.
- 2005- Restored vision in Briard dog persists longer than four years following RPE65 gene transfer 
- 2007- NEI-supported RPE65 human clinical trial began. This study was designed to assess the safety of using a modified adeno-associated viral vector (rAAV2-hRPE65) to deliver the normal RPE65 gene to the retina.
- Principal Investigators: Dr. Samuel Jacobson, University of Pennsylvania & Dr. Barry Byrne, University of Florida, Gene Vector Specialist: Dr. William Hauswirth, University of Florida, Surgeon: Dr. Shalesh Kaushal, University of Florida.
- 2008- Initial results from two clinical trials were published in the New England Journal of Medicine. Trials were conducted by the Children’s Hospital of Philadelphia (CHOP) and the University College of London. The first of the NEI-supported RPE65 human clinical trial completed. (Three patients treated.) Promising results published in Proceeding of the National Academy of Sciences (September 22) and Human Gene Therapy (September 7). 
- 2009- One-year results from the NEI-supported RPE65 human clinical trial published in Human Gene Therapy and the New England Journal of Medicine. All three patients remained healthy and maintained previous visual gains. One patient also noticed a visual improvement that helped her perform daily tasks.
Results from early LCA clinical studies represent one of the first steps toward the use of gene transfer therapy for an inherited form of blindness.
Outcome and Treatment
New Research Development
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