Submit a Letter to the Editor for:
T Wang, A H Milam, G Steel, D Valle
J Clin Invest. 1996;
97(12):2753
doi:10.1172/JCI118730
Abstract |
Full text
|
PDF
G
yrate atrophy (GA) of the choroid and retina is a blinding chorioretinal degeneration caused by deficiency of ornithine delta-aminotransferase (OAT). The phenotype of GA is characterized by progressive concentric reduction of the visual fields and ornithine accumulation. To understand better the pathogenesis of GA and to develop a model to test therapeutic strategies, we produced an OAT-deficient mouse by gene targeting. Like human GA patients, adult OAT-deficient mice exhibit chronic hyperornithinemia to levels 10-15-fold above normal and massive ornithinuria. Slowly progressive retinal degeneration is reflected by a gradual decline in electroretinogram amplitudes over the first 12 mo of life. At 2 mo, the retinal pigment epithelium is histologically normal, but electron microscopy reveals sporadic degeneration of scattered pigment epithelial cells. By 6 mo there are more diffuse abnormalities of the pigment epithelium with accumulation of large phagosomes and crystalloid inclusions. Although morphologically normal at 2 mo, the photo-receptor outer segments become highly disorganized and shortened to 60% of control length by 10 mo. Additionally, there is cumulative loss of the photoreceptor cells, which reaches 33% by 10 mo and is most pronounced in the central region of the retina. Our results indicate that retinal pigment epithelial cells are the initial site of insult in GA and that the OAT-deficient mouse is an excellent animal model of GA in human patients.
Guidelines:
The Editorial Board will only consider letters that we deem relevant and of interest to our readers. We will not post data that have not been subjected to peer review, nor will we post letters that are essentially a reiteration of another letter. All accepted letters will be posted on our website within one week of acceptance. The Editors reserve the right to edit any letter for length, content, and clarity. Authors of all accepted letters will be asked to preview any changes. Authors will be notified by e-mail if their letters were not accepted. As this is a final decision, no appeals will be considered.
Specific requirements: All letters must be 400 words or fewer. You may enter the letter as plain text or HTML, if you wish. The author's name and e-mail address are required, and will be posted with the letter. All possible conflicts of interest must be noted, even if they are not posted. If you wish to include a figure (keep in mind that non-peer-reviewed data will not be posted), please contact the editor directly at editors@the-jci.org.
