| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Li, Tao Ufret-Vincenty, Rafael L. He, Yuguang Chen, Xiao Zhang, Kaiyan Wang, Cynthia Xin-Zhao Gou, Darlene Zhao, Biren Aredo, Bogale |
| Description |
Country affiliation: United States Author Affiliation: Aredo B ( Department of Ophthalmology UT Southwestern Medical Center, Dallas, Texas, United States.); Li T ( Department of Ophthalmology UT Southwestern Medical Center, Dallas, Texas, United States 2Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.); Chen X ( Department of Ophthalmology UT Southwestern Medical Center, Dallas, Texas, United States.); Zhang K ( Department of Ophthalmology UT Southwestern Medical Center, Dallas, Texas, United States.); Wang CX ( Department of Ophthalmology UT Southwestern Medical Center, Dallas, Texas, United States.); Gou D ( Department of Ophthalmology UT Southwestern Medical Center, Dallas, Texas, United States.); Zhao B ( Department of Ophthalmology UT Southwestern Medical Center, Dallas, Texas, United States.); He Y ( Department of Ophthalmology UT Southwestern Medical Center, Dallas, Texas, United States.); Ufret-Vincenty RL ( Department of Ophthalmology UT Southwestern Medical Center, Dallas, Texas, United States.) |
| Abstract |
PURPOSE: Variants of complement factor H (Cfh) affecting short consensus repeats (SCRs) 6 to 8 increase the risk of age-related macular degeneration. Our aim was to explore the effect of expressing a Cfh variant on the in vivo susceptibility of the retina and RPE to oxidative stress and inflammation, using chimeric Cfh transgenic mice (chCfhTg). METHODS: The chCfhTg and age-matched C57BL/6J (B6) mice were subjected to oxidative stress by either normal aging, or by exposure to a combination of oral hydroquinone (0.8% HQ) and increased light. Eyes were collected for immunohistochemistry of RPE-choroid flat mounts and of retinal sections, ELISA, electron microscopy, and RPE/microglia gene expression analysis. RESULTS: Aging mice to 2 years led to an increased accumulation of basal laminar deposits, subretinal microglia/macrophages (MG/MΦ) staining for CD16 and for malondialdehyde (MDA), and MDA-modified proteins in the retina in chCfhTg compared to B6 mice. The chCfhTg mice maintained on HQ diet and increased light showed greater deposition of basal laminar deposits, more accumulation of fundus spots suggestive of MG/MΦ, and increased deposition of C3d in the sub-RPE space, compared to controls. In addition, chCfhTg mice demonstrated upregulation of NLRP3, IP-10, CD68, and TREM-2 in the RNA isolates from RPE/MG/MΦ. CONCLUSIONS: Expression of a Cfh transgene introducing a variant in SCRs 6 to 8 was sufficient to lead to increased retinal/RPE susceptibility to oxidative stress, a proinflammatory MG/MΦ phenotype, and a proinflammatory RPE/MG/MΦ gene expression profile in a transgenic mouse model. Our data suggest that altered interactions of Cfh with MDA-modified proteins may be relevant in explaining the effects of the Cfh variant. |
| ISSN |
01460404 |
| e-ISSN |
15525783 |
| DOI |
10.1167/iovs.14-16089 |
| Journal |
Investigative Opthalmology & Visual Science |
| Issue Number |
6 |
| Volume Number |
56 |
| Language |
English |
| Publisher |
Association for Research in Vision and Ophthalmology |
| Publisher Date |
2015-06-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Complement Factor H Genetics Microglia Cytology Oxidative Stress Retina Metabolism Aging Physiology Animals Antigens, Cd Antigens, Differentiation, Myelomonocytic Carrier Proteins Chemokine Cxcl10 Disease Models, Animal Inflammation Physiopathology Membrane Glycoproteins Mice Mice, Inbred C57bl Mice, Transgenic Receptors, Immunologic Retinal Pigment Epithelium Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Ophthalmology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Ophthalmology Sensory Systems Cellular and Molecular Neuroscience |
