Macrophage depletion using CL(2)MDP-lip reduces size, cellularity, and vascularity of CNV. This observation supports the hypothesis that macrophages contribute to the severity of CNV lesions.
Exposure to cigarette smoke or the smoke-related redox molecule, HQ, results in the formation of sub-RPE deposits, thickening of Bruch's membrane, and accumulation of deposits within Bruch's membrane. Smoke-related oxidants may be another oxidative injury stimulus to the choriocapillaris and RPE, and may explain the association between cigarette smoking and early AMD.
To evaluate the activation state of macrophage function in patients with age-related macular degeneration (AMD) by quantifying the production of the proinflammatory and angiogenic factor tumor necrosis factor ␣ (TNF-␣) and by correlating its expression with dry and wet AMD. Methods: Circulating monocytes were obtained from the blood of patients with AMD or age-matched control subjects by gradient centrifugation. The monocytes were then analyzed for either TNF-␣ release from cultured macrophages in response to retinal pigment epitheliumderived blebs and cytokines or TNF-␣ messenger RNA content by reverse transcriptase-polymerase chain reaction. Results: In human monocytes obtained from controls and AMD patients, TNF-␣ was expressed by freshly isolated monocytes and produced by macrophages in culture after stimulation with retinal pigment epithelium-derived blebs. However,widevariabilityinTNF-␣expressionwasobserved among different patients. Patients with monocytes that expressed the greatest amount of TNF-␣ demonstrated higher prevalence of choroidal neovascularization. Conclusions: Both controls and AMD patients vary in the activation state (defined as TNF-␣ expression) of circulating monocytes. Partially active monocytes, defined as high TNF-␣ expression, may be a biomarker to identify patients at risk for formation of choroidal neovascularization. Clinical Relevance: Early diagnostic testing may prove useful to detect those patients who will progress to the more severe complications of the disease.
Nicotine increases size and severity of experimental CNV in the present mouse model, possibly by potentiating PDGF-mediated upregulation of proliferation of choroidal smooth muscle cells or by other mechanisms. These results suggest that non-neuronal nicotinic receptor activation probably mediates some of the harmful effects of cigarette smoking in wet AMD.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.