title: A rat model for studying the biological effects of circulating LDL in the choriocapillaris-BrM-RPE complex.
abstract: Retention of apolipoprotein B-containing lipoproteins in Bruch's membrane (BrM) is believed to be important in early age-related macular degeneration (AMD). The origin of the lipoproteins in BrM is a hot topic in AMD research. Some studies hypothesize an intraocular origin. BrM is in direct contact to the choriocapillaris; a plasma origin has also been suggested for the low-density lipoprotein (LDL) particles. We developed an animal model to study the biological effects of circulating LDL on the retina. After injection of LDL for 7 days, our results showed evidence of circulating apolipoprotein B100 retention in BrM and showed induction of early AMD-like alterations in the rat retina, such as thickening of BrM, photoreceptor TUNEL-positive cells, and inflammatory cell infiltration. In vitro assays showed that oxidized LDL (ox-LDL) treatment decreased ARPE-19 cell viability in a dose-dependent manner and that 10 mg/L ox-LDL induced marked apoptosis. The ratio of matrix metalloproteinase-2 to tissue inhibitors of metalloproteinase-3 was dysregulated after LDL and ox-LDL treatment in ARPE-19 cells, which can produce profound changes in the extracellular matrix, including thickening of and deposit formation in BrM. The observation that circulating LDL may be a significant, but not complete, origin of the lipoprotein in BrM suggests that these findings can be readily exploited for the development of new model systems and the future benefit of patients with AMD.
authors: Department of Ophthalmology, Shanghai First People's Hospital, Medical School, Shanghai Jiaotong University, Shanghai, China.
authors: Lili
authors: L
authors: Yin
authors: Yuhua
authors: Y
authors: Shi
authors: Xiaojuan
authors: X
authors: Liu
authors: Hongmei
authors: H
authors: Zhang
authors: Yuanyuan
authors: Y
authors: Gong
authors: Qing
authors: Q
authors: Gu
authors: Xingwei
authors: X
authors: Wu
authors: Xun
authors: X
authors: Xu
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D053299:Apolipoprotein B-100 / Q000378:metabolism*; D016570:Bruch Membrane / Q000098:blood supply / Q000187:drug effects* / Q000648:ultrastructure; D002196:Capillaries / Q000187:drug effects*; D004596:Electroretinography; D007111:Immunity, Cellular / Q000502:physiology; D007376:Interleukin-2 / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000008:administration & dosage / Q000494:pharmacology*; D008268:Macular Degeneration / Q000139:chemically induced*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008854:Microscopy, Electron; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000098:blood supply / Q000187:drug effects* / Q000648:ultrastructure; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D053299:Apolipoprotein B-100; D007376:Interleukin-2; D008055:Lipids; D008077:Lipoproteins, LDL; D019717:Tissue Inhibitor of Metalloproteinase-3; C099252:oxidized low density lipoprotein; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat