Loading...
Please wait, while we are loading the content...
Similar Documents
Abnormal vascularization in mouse retina with dysregulated retinal cholesterol homeostasis.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Omarova, Saida Charvet, Casey D. Reem, Rachel E. Mast, Natalia Zheng, Wenchao Huang, Suber S. Peachey, Neal S. Pikuleva, Irina A. |
| Copyright Year | 2012 |
| Abstract | Several lines of evidence suggest a link between age-related macular degeneration and retinal cholesterol maintenance. Cytochrome P450 27A1 (CYP27A1) is a ubiquitously expressed mitochondrial sterol 27-hydroxylase that plays an important role in the metabolism of cholesterol and cholesterol-related compounds. We conducted a comprehensive ophthalmic evaluation of mice lacking CYP27A1. We found that the loss of CYP27A1 led to dysregulation of retinal cholesterol homeostasis, including unexpected upregulation of retinal cholesterol biosynthesis. Cyp27a1-/- mice developed retinal lesions characterized by cholesterol deposition beneath the retinal pigment epithelium. Further, Cyp27a1-null mice showed pathological neovascularization, which likely arose from both the retina and the choroid, that led to the formation of retinal-choroidal anastomosis. Blood flow alterations and blood vessel leakage were noted in the areas of pathology. The Cyp27a1-/- retina was hypoxic and had activated Müller cells. We suggest a mechanism whereby abolished sterol 27-hydroxylase activity leads to vascular changes and identify Cyp27a1-/- mice as a model for one of the variants of type 3 retinal neovascularization occurring in some patients with age-related macular degeneration. |
| Starting Page | 725 |
| Ending Page | 734 |
| Page Count | 10 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.jci.org/articles/view/63816/version/2/pdf/render |
| Alternate Webpage(s) | http://dm5migu4zj3pb.cloudfront.net/manuscripts/63000/63816/JCI63816.v2.pdf |
| PubMed reference number | 22820291v1 |
| Alternate Webpage(s) | https://doi.org/10.1172/JCI63816 |
| DOI | 10.1172/jci63816 |
| Journal | The Journal of clinical investigation |
| Volume Number | 122 |
| Issue Number | 8 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Anabolism Blood Vessel CYP27A1 gene Cholesterol Homeostasis Choroid Extravasation Eye Hypoxia Macular degeneration Pathologic Neovascularization Patients Retina Retinal Diseases Retinal Neovascularization Retinal Pigments Sterol 26-Hydroxylase, Mitochondrial Structure of retinal pigment epithelium cholesterol biosynthesis vitamin D3 25-hydroxylase |
| Content Type | Text |
| Resource Type | Article |
