The hallmark lesions of age-related macular degeneration (AMD) are drusen and basal linear deposit which are lipid substances deposited in Bruch membrane or the compartment on the Bruch membrane. There is a prevailing hypothesis that lipid and its oxidized derivant deposited in retina may have important roles in the pathogenesis of AMD. Lipid oxidation products are toxic, may affect the adjacent cells, induce inflammation, and trigger neovascularization.7-ketocholestoral (7KCh), a naturally occurring oxidized form of cholesterol, had been found to be toxic to retinal cells and able to induce chronic inflammation, which may play a critical role in the development of AMD. However the precise mechanism remains to be elucidated. Thus we will make a brief review of 7KCh and its association with AMD.
Macular pigment (MP) is composed of lutein, zeaxanthin, and meso-zeaxanthin, which accumulate mainly at the macula. MP has antioxidant function and can filtering blue wave. Measurement of MP is about its optical density, that is, macular pigment optical density (MPOD). This review summarizes the function and clinical use of MP and MPOD. Researches has show that MPOD is related to some ocular disease such as age-related macular degeneration, macular telangiectasia type 2, diabetic retinopathy, Stargardt disease et al. MPOD can be used in the judgment of clinical diagnosis, treatment effect. The specific mechanism of MP metabolism in the retina and in the pathogenesis of the disease, genotype specific nutritional therapy of xanthophyll, the establishment of a database combined with artificial intelligence and the rapid and convenient MP determination are all issues of great contention that need to be resolved.
Dysregulation and activation of immune processes are important in age-related macular degeneration (AMD) pathogenesis. The single nucleotide polymorphism of complement factor H is widely recognized as a risk factor to AMD. Over-activation of nod-like receptor3 and polymorphism of Toll-Like Receptor 3 also associated with AMD. Except for innate immune processes, adaptive immunity also play a critical role in AMD, a growing body of evidence supports that auto-antibodies and T cells are related with AMD. Additionally A2E and lipid oxidation byproducts might also have a role in AMD pathogenesis.
ObjectiveTo observe the expression of vascular endothelial growth factor (VEGF), fibrogenic mediators and inflammatory mediators in the retinal pigment epithelium (RPE)-choroid complex of mice with experimental subretinal fibrosis. MethodsBy subretinal injection of inflammatory macrophages after retinal photocoagulation, experimental subretinal fibrosis was induced in 64 adult C57BL/6(B6) female mice (7-8 weeks). Masson staining and glial fibrillary acidic protein (GFAP) staining of choroidal wholemont were performed to verify that the subretinal fibrosis at day 7 after subretinal injection. Before subretinal injection and at day 1, 2, 3, 5 and 7 after subretinal injection, the mRNA expression level of VEGF, transforming growth factor (TGF)-β1, TGF-β2, TGF-β3, interleukin (IL)-6, IL-10 and IL-13 in RPE-choroid complex were evaluated by quantitative reverse transcription-polymerase chain reaction. Enzyme-linked immune sorbent assay was next used to detect protein expression of these factors. ResultsAt seven days after subretinal injection of inflammatory macrophages, experimental subretinal fibrosis was detected by Masson staining and GFAP staining. The mRNA level of VEGF, TGF-β1 and TGF-β2 reached the peak at day 5 after modeling, while the mRNA expression of IL-6, IL-10, IL-13 reached the peak at day 2 after modeling. TGF-β3 mRNA was not detected either in naive mice or during the development of experimental subretinal fibrosis. At day 2, 3, 5 and 7 after modeling, compared with the pre-modeling, the mRNA expression of VEGF (t=2.38, 3.65, 4.03, 2.26), TGF-β1 (t=2.58, 2.30, 3.89, 4.15) and TGF-β2 (t=4.37, 4.20, 3.77, 3.98) were significantly increased (P < 0.05). At day 1, 2 and 3 after modeling, compared with the pre-modeling, the mRNA expression of IL-6 were significantly increased (t=2.36, 4.54, 4.01; P < 0.05). At day 2 and 3 after modeling, compared with the pre-modeling, the mRNA expression of IL-10 and IL-13 were significantly increased (t=3.87, 4.20, 2.44, 2.58; P < 0.05). At day 5 after modeling, compared with the pre-modeling, the protein expression of VEGF, total TGF-β1, active TGF-β1, total TGF-β2 and active TGF-β2 were significantly increased (t=2.57, 3.37, 2.45, 3.83, 2.74; P < 0.05). IL-6, IL-10 and IL-13 protein were not detected at pre-modeling eyeballs, but were found at day 2 after modeling. ConclusionThe expression of VEGF, fibrogenic mediators and inflammatory mediators in RPE-choroid complex in mice with experimental subretinal fibrosis are increase significantly.
Choroidal neovascularization is the leading causes of central vision loss in wet age-related macular degeneration (wAMD) patients. Smoking not only aggravates the incidence and severity of the choroidal neovascularization of wAMD, but also affects the clinical treatment, making the prognosis worse. Nicotine, as an important harmful substance in tobacco, is an easily addictive and highly toxic alkaloid. Animal experiments and clinical studies have confirmed that nicotine can aggravate wAMD by mediating angiogenesis through nicotinic acetylcholine receptor, bone marrow blasts, inflammation, complement system, etc. Therefore, in order to early take appropriate intervention measures to prevent and delay the development, we should actively explore the exact pathogenesis by which nicotine aggravates the choroidal neovascularization.
Photoreceptor cells are special retinal neurons with photo-transformation ability. Loss of photoreceptors in age-related macular degeneration (AMD) is secondary to RPE loss, leakage of serum components from the neovascularization and scar formation, which is one of the main mechanisms of irreversible visual impairment in patients with AMD. Many studies have shown that inflammatory environment is involved in the process of photoreceptor cell death. Aging, photooxidation injury and other factors affects the retinal microenvironment through different levels of mechanisms such as retinal pigment epithelial cells, retinal glial cells, hematogenous macrophages and inflammatory factors, which results in photoreceptor injuries and participates in the progression of AMD by drusen formation and neovascularization. This study reviews the research status and progress of inflammation and photoreceptor cell death, and provides new ideas for exploring the blinding mechanism and treatment strategies of AMD.