2012 Group Project 5

From Embryology

Abnormal Vision


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 primordium and sulcus developing in the neural folds at Carnegie stage 10 or around 22 days. Stage 11, or 24 days, sees the rostral neuropore closing and the optic vesicle forming from the optic sulcus. Only at stage 12 will you see the beginning formation of the optic placode as the optic vesicle sits near the surface ectoderm. [1] [2] At stage 13, 28 days, a thickened surface ectoderm layer has developed on top of the optic vesicle, we know this to be the lens disc. The retinal disc (soon to be optic cup) has appeared on the wall of the optic vesicle.[3] As development continues through to Carnegie stage 14, the retinal disc is invaginated to form then optic cup and the lens pit forms. This lens pit closes in stage 15 and the optic cup and lens vesicle seem to bulge and press against the surface as the primary vitreous body begins to form.[4] [5] This contour of the optic cup progresses until it is quite noticeable in stage 16, small grooves can also be seen above and below the eye. The retina differentiates at around stage 17 and the primary lens fibers obliterate the cavity of the lens vesicle filling the space at stage 18. The pupillary membrane and the layers of the cornea develop from stages 19-21. At stage 20 the retinal nerve fiber layer appears and grow towards the brain.[6] As the grooves above and below the eye develop and deepen in stage 17-19, eyelid folds develop, which soon turn into actual eyelids at around stage 19 and continue to develop further and grow slowly at stage 22. The eyelids close completely at stage 23.[7]

Retinal Development

Abnormal development


Leber Congenital Amaurosis

Leber Congenital Amaurosis (LCA) is an inherited retinal degenerative disorder that causes blindness or loss of sight at birth.[8] LCA has a recessive pattern of inheritance where there is a 25% chance for a child to contract LCA.[9]


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).[10]

Research Timeline

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 [11]
  • 1932-34- George Wald, Ph.D. first identified vitamin A in the retina during a National Research Council fellowship in biology [12]
  • 1965- Human adeno-associated virus (AAV) was discovered.[13]
  • 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.[14]
  • 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.[15]
  • 1993- Dr. T. Michael Redmond of the NEI's Laboratory, cloned RPE65, a protein necessary for processing vitamin A in the visual cycle.[16]
  • 1997- RPE65 gene mutations identified as the cause of congenital blindness in some children with Leber congenital amaurosis.[17]
  • 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.[18]
  • 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.[19]
  • 2005- Restored vision in Briard dog persists longer than four years following RPE65 gene transfer [20]
  • 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.[21]
  • 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). [22]
  • 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.[23]




Outcome and Treatment

New Research Development

Congenital Cataracts




  1. Anthony A. Pearson The Development of the Eyelids Journal of Anatomy: 1980, 130, 1, pp. 35-42
  2. Ronan O'Rahilly The Prenatal Development of the Human Eye Experimental Eye Research 1975, 21, pp. 93-112
  3. Ronan O'Rahilly The Prenatal Development of the Human Eye Experimental Eye Research 1975, 21, pp. 93-112
  4. Ronan O'Rahilly The Prenatal Development of the Human Eye Experimental Eye Research 1975, 21, pp. 93-112
  5. Anthony A. Pearson The Development of the Eyelids Journal of Anatomy: 1980, 130, 1, pp. 35-42
  6. Ronan O'Rahilly The Prenatal Development of the Human Eye Experimental Eye Research 1975, 21, pp. 93-112
  7. Anthony A. Pearson The Development of the Eyelids Journal of Anatomy: 1980, 130, 1, pp. 35-42
  8. http://www.blindness.org/index.php?view=article&catid=38%3Aother-retinal-diseases&id=253%3Aleber-congenital-amaurosis&option=com_content&Itemid=88
  9. http://www.blindness.org/index.php?view=article&catid=38%3Aother-retinal-diseases&id=253%3Aleber-congenital-amaurosis&option=com_content&Itemid=88
  10. http://www.springerlink.com/content/rmj766pjrq130011/
  11. http://www.nei.nih.gov/lca/timeline.asp
  12. http://www.nei.nih.gov/lca/timeline.asp
  13. http://www.nei.nih.gov/lca/timeline.asp
  14. http://www.nei.nih.gov/lca/timeline.asp
  15. http://www.nei.nih.gov/lca/timeline.asp
  16. http://www.nei.nih.gov/lca/timeline.asp
  17. http://www.nei.nih.gov/lca/timeline.asp
  18. http://www.nei.nih.gov/lca/timeline.asp
  19. http://www.nei.nih.gov/lca/timeline.asp
  20. http://www.nei.nih.gov/lca/timeline.asp
  21. http://www.nei.nih.gov/lca/timeline.asp
  22. http://www.nei.nih.gov/lca/timeline.asp
  23. http://www.nei.nih.gov/lca/timeline.asp

External Links

External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.

--Mark Hill 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

2012 Projects: Vision | Somatosensory | Taste | Olfaction | Abnormal Vision | Hearing