Age-related macular degeneration is one of the major causes of blindness in the elderly. As an important pathway of cell metabolism, autophagy maintains intracellular homeostasis through the degradation and recycle of damaged organelles and macromolecules. Understanding its mechanism may promote discoveries to delay aging process, reduce the incidence of age-related diseases. In mammals, silent information regulator protein 6 (SIRT6) plays its deacetylase and ribonucleotransferase activity in multiple signaling pathways, including inhibition of cellular senescence, tumorigenesis, metabolic diseases, regulating cellular lifespan. It has a significant impact on the structure and function of tissues and organs. SIRT6 regulates intracellular autophagy mainly through the insulin-like growth factor-protein kinase B-mammalian target of rapamycin, reducing the accumulation of toxic metabolites and cellular senescence. The function of SIRT6 in age-related macular degeneration need to be combined with the genetic background, pathogenesis, clinical manifestations and other aspects of the disease, and it is expected to be further studied in subsequent studies.
The therapeutic effect of anti-vascular endothelial growth factor (VEGF) for neovascular age-related macular degeneration (nAMD) was determined by a number of factors. Comprehensive thorough analysis of clinical features, imaging results and treatment response can predict the potential efficacy and possible vision recovery for the patient, and also can optimize the treatment regime to make a personalized therapy plan. Precise medicine with data from genomics, proteomics and metabolomics study will provide more objective and accurate biology basis for individual precise treatment. The future research should focus on comprehensive assessment of factors affecting the efficacy of anti-VEGF therapy, to achieve individualized precise diagnosis and treatment, to improve the therapeutic outcome of nAMD.
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.
Objective To compare the characteristics of the ocular fundus of exudative age-related macular degeneration (AMD) with polypoidal choroidal vasculopathy (PCV). Methods The photographs of ocular fundus of 123 patients (137 eyes) with exudative AMD and 42 patients (48 eyes) with PCV diagnosed by fundus photography, fundus fluorescein angiography (FFA), and indocyanine green angiography (ICGA) were retrospectively analyzed. Results In 137 eyes with exudative AMD, 16 eyes (11.7%) had classic neovascularization (CNV), 121 (88.3%) had occult CNV. In the eyes with occult CNV, 42 eyes (34.7%) had hot spots, 74 eyes (61.2%) showed plaque hyperfluorescences and 2 eyes (1.7%) had hot spots with PCV in ICGA. In 48 eyes with PCV, 7 eyes (14.6%) had subretinal reddish-orange lesions, 2 eyes (4.2%) of the polypoidal dilations with branching vascular network were detected with FFA, 36 eyes (75.0%) demonstrated polypoidal dilations with branching vascular network, and 12 eyes (25.0%) showed scattered polypoidal dilations without identifiable continuous branching vascular network, 16 eyes (33.3%) had the polypoidal dilations resembling a cluster of grapes, and 32 eyes (66.3%) showed the polypoidal dilations as several solitary round aneurismal dilations. The polypoidal dilations showed either a washout of the dye from the polyp with staining of its walls or staining of the dye in the late phase of ICGA. Conclusions The different features of exudative AMD and PCV in the ICGA, and the PCV with subretinal reddish-orange lesions are useful in the differentiate diagnosis of the both diseases. (Chin J Ocul Fundus Dis，2004，20：307-309)
Microparticles are small vesicles that are released by budding of the plasma membrane during cellular activation and apoptotic cell breakdown. A spectrum of cell types can release microparticles including endothelial cells, platelets, macrophages, lymphocytes and tumor cells. Biological effects of microparticles mainly include procoagulant activity, inhibition of inflammation and cancer progression. The present study shows that vitreous microparticles isolated from proliferative diabetic retinopathy (PDR) stimulated endothelial cell proliferation and increased new vessel formation, promoting the pathological neovascularization in PDR patients. Oxidative stress induces the formation of retina pigment epithelium-derived microparticles carrying membrane complement regulatory proteins, which is associated with drusen formation and age related macular degeneration. Microparticles from lymphocyte (LMP) play an important role in anti-angiogenesis by altering the gene expression pattern of angiogenesis-related factors in macrophages. Besides, LMP are important proapoptotic regulators for retinoblastoma cells through reduction of spleen tyrosine kinase expression and upregulation of the p53-p21 pathway which ultimately activates caspase-3. However, how to apply the microparticles in the prevention and treatment of retinal diseases is a major challenge, because the study of the microparticles in the fundus diseases is still limited. Further studies conducted would certainly enhance the application of microparticles in the fundus diseases.
Flicker and photopic eletroretinogram(ERG)were recorded for 45 eyes of dry type of age-related macular degeneration(AMD)and 24 eyes of wet type of AMD respectively,the amplitud and phase of fundamental response compomeng(30Hz)by discrete Fourier tranform(DFT)were analysed.The abnormality ratios of phases and amplitudes in fundamental responses,amplitudes of photopic white or red b-waves were 48.89%,8.89%,10.11% and 8.89% respectively.The visual acuities of 24 eyes were 1.0 or better,the abnormality ratios of phases were up to 37.50%.These suggest that the change of phases is a sensitive method for detecting the early abnormality of visual function in AMD.The abnormality ratios of phases and amplitudes in fundamental responses were 62.5% and 45.84% in wet type of AMD.The differences between dry type and wet type in amplitudes of fundamental responses and photopic b-waves were statistically significant(P＜0.01).This shows that the change of amplitudes is associated with the degree of pathological change of AMD. （Chin J Ocul Fundus Dis,1996,12: 41-43）