吸烟对年龄相关性黄斑变性发生和发展的影响

年龄相关性黄斑变性(AMD)的视力损失多由视网膜色素上皮细胞的凋亡和光感受器的退化引起。主动、被动吸烟会增加AMD发病率及向晚期AMD进展的风险,并且影响湿性AMD的治疗效果。吸烟可引起脉络膜血管收缩、血管阻力增加、血管内皮功能障碍、脉络膜和神经节细胞复合体变薄,导致脉络膜和视网膜血管反应性受损。香烟中的尼古丁可导致血管内皮生长因子(VEGF)过度表达,VEGF增加血管通透性及诱导内皮细胞增生,从而诱发脉络膜新生血管(CNV)的形成。吸烟可诱发氧化应激,导致氧化损伤,减少补体因子H表达,增加膜攻击复合物,导致巨噬细胞功能异常,促进玻璃膜疣形成,诱导CNV形成。因此,在控制AMD发生、预防CNV形成中应充分认识吸烟与CNV以及AMD的关系,这对AMD的早期预防及探索更有效的治疗途径有着重要的意义。     

A genetic approach to stratification of risk for age-related macular degeneration

The genetic determinants of age-related macular degeneration (AMD) are reviewed and a novel approach to risk determination based upon inherited genetic polymorphisms and smoking history is presented. Although AMD was long thought to have primarily an environmental etiology, genetic variation is now known to account for the majority of the disease risk, with variations in the genes of the complement pathways playing a prominent role. Independent and validated clinical studies have implicated the C3 gene and its regulator, complement factor H (1q31.1), complement component 2 (6q21.33), and complement factor B (6q21.33). Subtle variations in complement activity increase the risk of symptomatic macular inflammation with age. A second group of AMD-associated genetic markers may aggravate complement-mediated inflammation by permitting retinal oxidative damage. Variation within the chromosomal site (10q26) coding a mitochondrial-associated protein (age-related maculopathy susceptibility 2) and an independent variation within the mitochondrial genome itself (A4917G) suggest a contributing pathophysiological role of retinal oxidative stress. A genetic panel of disease-susceptibility markers and smoking history can identify a group of individuals with greater than 65% lifetime risk of AMD. The introduction of genetic marker testing into clinical practice may identify patients with early disease who may be aided by presymptomatic monitoring or inclusion into trials of newer prophylactic agents.     

Serum levels of antioxidants and age-related macular degeneration

A number of reports have suggested that oxidative damage in the retina may contribute to the pathogenesis of Age-related macular degeneration (AMD). The present study was designed to investigate the hypothesis that serum levels of the antioxidants, Vitamin E and selenium are related to the pathogenesis of AMD. Fasting bloods were obtained from 80 patients with AMD and 86 controls. Assays for serum levels of Vitamin E, selenium, cholesterol and triglycerides were performed. Assessment of patients and controls was based upon eye examination, fundus photography and medical history. No significant difference was found in serum levels of Vitamin E between subjects and controls, however, there was a borderline association between AMD and both serum selenium levels and current smoking status. The results suggest that if oxidative damage is a factor in the pathogenesis of AMD, it is not reflected in serum levels of Vitamin E; further studies are required to clarify the possible relationship between serum selenium levels, smoking and AMD.     

年龄相关性黄斑变性抗氧化剂治疗进展

年龄相关性黄斑变性是一种随年龄增长而发病率逐渐上升的黄斑部疾病,目前认为其发病机制与患者的年龄、遗传、吸烟、饮食、氧化应激、免疫炎症反应、心血管疾病等因素有关,其中氧化应激作用与年龄相关性黄斑变性密切相关.抗氧化剂治疗为防治年龄相关性黄斑变性提供了一种策略,为缓解和预防年龄相关性黄斑变性的研究提供了新思路.     

Oxidative damage and protection of the RPE

This review provides a model for the role of oxidative stress in the etiology of age-related macular degeneration (AMD). Epidemiological studies of diet, environmental and behavioral risk factors suggest that oxidative stress is a contributing factor of AMD. Pathological studies indicate that damage to the retinal pigment epithelium (RPE) is an early event in AMD. In vitro studies show that oxidant treated RPE cells undergo apoptosis, a possible mechanism by which RPE cells are lost during early phase of AMD. The main target of oxidative injury seems to be mitochondria, an organelle known to accumulate genomic damages in other postmitotic tissues during aging. The thiol antioxidant GSH and its amino acid precursors protect RPE cells from oxidant-induced apoptosis. Similar protection occurs with dietary enzyme inducers which increase GSH synthesis. These results indicate that therapeutic or nutritional intervention to enhance the GSH antioxidant capacity of RPE may provide an effective way to prevent or treat AMD.     

Smoking and age related macular degeneration: the number of pack years of cigarette smoking is a major determinant of risk for both geographic atrophy and choroidal neovascularisation

BACKGROUND/AIMS: There is evidence that smoking is a risk factor for age related macular degeneration (AMD). However, not all studies have demonstrated this association and several key questions about the role of smoking in AMD have still to be determined. The aim of this study was to further investigate this relation for both choroidal neovascularisation (CNV) and geographic atrophy (GA). METHODS: To investigate the relation between smoking and the risk of developing age related macular degeneration (AMD) in white people, 435 cases with end stage AMD were compared with 280 controls. All subjects had graded stereoscopic colour fundus photography and AMD was defined as the presence of GA or CNV. Smoking history was assessed using multiple parameters in a detailed questionnaire. RESULTS: Comparison of current and former smokers with non-smokers was consistent with smoking being a risk factor for AMD but did not reach statistical significance. There was a strong association between AMD and pack years of cigarette smoking (p = 0.002), the odds ratio increasing with the amount smoked; for subjects with more than 40 pack years of smoking the odds ratio was 2.75 (95% CI 1.22 to 6.20) compared with non-smokers. Both types of AMD showed a similar relation; smoking more than 40 pack years of cigarettes was associated with an odds ratio of 3.43 (95% CI 1.28 to 9.20) for GA and 2.49 (95% CI 1.06 to 5.82) for CNV. Stopping smoking was associated with reduced odds of AMD and the risk in those who had not smoked for over 20 years was comparable to non-smokers. The risk profile was similar for males and females. Passive smoking exposure was associated with an increased risk of AMD (OR 1.87; 95% CI 1.03 to 3.40) in non-smokers. CONCLUSIONS: The authors have demonstrated a strong association between the risk of both GA and CNV and pack years of cigarette smoking. This provides support for a causal relation between smoking and AMD. They also show an increased risk for AMD in non-smokers exposed to passive smoking. Stopping smoking appears to reduce the risk of developing AMD.     

微小RNA与年龄相关性黄斑变性发病的关系

微小RNA (miRNA)是指一种小的内源性非编码RNA分子,其异常表达与年龄相关性黄斑变性(age-related macular degeneration,AMD)发生发展密切相关.miRNA在AMD的炎性反应、氧化应激损伤、淀粉样蛋白及脉络膜新生血管形成等病变过程中贯穿始终.这些发现可能为AMD的早期诊断、治疗及预后判断提供新的可能性.     

Effects of systemic drugs on the development and progression of age-related macular degeneration

Age-related macular degeneration (AMD) is the leading cause of severe loss of central vision among people over 50. The pathophysiology of the disease is multifactorial and can be attributed to genetics, aging, inflammation, environmental factors, and lifestyle factors including smoking, diet, obesity, and alcohol consumption. While there is no treatment for dry AMD, the current standard treatment for wet AMD is an intraocular injection of anti-vascular endothelial growth factor—an effective, yet expensive, therapy that requires ongoing treatment. As the aging population continues to grow, and AMD diagnoses continue to rise, new treatments should be explored to reduce vision complications and decrease treatment burdens. Many systemic conditions have progressive pathological changes that may affect AMD, particularly those affecting systemic vasculature like diabetes and cardiovascular status. Consequently, systemic drugs used to treat coexistent systemic diseases may influence some of the pathogenic mechanisms of AMD and lead its progression or delay. In this review we explore the current literature to summarize the findings of the reported effects of antihypertensive, immunosuppressants, cholesterol lowering agents, nonsteroidal anti-inflammatory drugs, dopamine precursors, hypoglycemic agents, and anticoagulants on AMD.     

28,000 Cases of age related macular degeneration causing visual loss in people aged 75 years and above in the United Kingdom may be attributable to smoking

BACKGROUND: Age related macular degeneration (AMD) causing visual impairment is common in older people. Previous studies have identified smoking as a risk factor for AMD. However, there is limited information for the older population in Britain. METHODS: Population based cross sectional analytical study based in 49 practices selected to be representative of the population of Britain. Cases were people aged 75 years and above who were visually impaired (binocular acuity <6/18) as a result of AMD. Controls were people with normal vision (6/6 or better). Smoking history was ascertained using an interviewer administered questionnaire. RESULTS: After controlling for potentially confounding factors, current smokers were twice as likely to have AMD compared to non-smokers (odds ratio 2.15, 95% CI 1.42 to 3.26). Ex-smokers were at intermediate risk (odds ratio 1.13, 0.86 to 1.47). People who stopped smoking more than 20 years previously were not at increased risk of AMD causing visual loss. Approximately 28,000 cases of AMD in older people in the United Kingdom may be attributable to smoking. CONCLUSION: This is the largest study of the association of smoking and AMD in the British population. Smoking is associated with a twofold increased risk of developing AMD. An increased risk of AMD, which is the most commonly occurring cause of blindness in the United Kingdom, is yet another reason for people to stop smoking and governments to develop public health campaigns against this hazard.     

Exposure to Chlamydia pneumoniae infection and age-related macular degeneration: the Blue Mountains Eye Study

PURPOSE: To assess cross-sectional and longitudinal associations between exposure to Chlamydia pneumoniae infection and age-related macular degeneration (AMD) in the nested case-control sample drawn from the Blue Mountains Eye Study (BMES) cohort. METHODS: The BMES examined 3654 persons aged 49 to 97 years during 1992 through 1994 (BMES I survey). Survivors from this cohort (n = 2335; 75%) and 1174 persons who moved in this area or reached an eligible age were examined during 1997 through 2000 (BMES II survey, n = 3509). One hundred ninety-seven AMD cases and 433 control subjects matched for age, sex and smoking status, were drawn from the BMES II survey. Photographic macular grading followed the Wisconsin grading system. Plasma samples were analyzed with an enzyme-linked immunosorbent assay to determine antibody titers to the elementary bodies from C. pneumoniae AR39. Associations between seroreactivity to C. pneumoniae and prevalent and incident AMD were assessed by using logistic regression models. RESULTS: There were 159 early and 38 late AMD cases. Of them, 87 cases of early and 22 of late AMD developed between the baseline and follow-up examinations. After adjustment for age, gender, and smoking, no significant association was evident between C. pneumoniae antibody titer and any prevalent early or late AMD (OR 1.02, 95% CI 0.66-1.56 comparing upper with lower tertile of antibody titer). Findings were similar when early or late AMD was analyzed separately. Analysis confined to incident AMD also showed no significant association with the incidence of either early (OR 0.92, 95% CI 0.52-1.64) or late (OR 1.85, 95% CI 0.57-6.05) AMD. The results did not change after adjustment for family history of AMD and cardiovascular disease. CONCLUSIONS: In this nested case-control sample of an older Australian population we found no association between C. pneumoniae antibody titers and early AMD. The study has insufficient power to assess an association with late AMD.     

Alcohol consumption and the risk of age-related macular degeneration: a systematic review and meta-analysis

PURPOSE: To review systematically the evidence currently available on alcohol consumption and the risk of age-related macular degeneration (AMD). DESIGN: Systematic review and meta-analysis of observational studies. METHODS: Seven databases were searched systematically with no limits on the year or language of publication for prospective cohort studies. References identified from pertinent reviews and articles also were retrieved. Two reviewers independently searched the above databases and selected the studies using prespecified standardized criteria. These criteria included appropriate adjustment for age and smoking in the analysis. Of the 441 studies identified initially, five cohort studies met the selection criteria. Data extraction and study quality evaluation were performed independently by two reviewers and results were pooled quantitatively using meta-analytic methods. RESULTS: The five cohort studies included 136,946 people, among whom AMD developed in 1923 (1,513 early and 410 late). Pooled results showed that heavy alcohol consumption was associated with an increased risk of early AMD (pooled odds ratio, 1.47; 95% confidence interval, 1.10 to 1.95), whereas the association between heavy alcohol consumption and risk of late AMD was inconclusive. There were insufficient data to evaluate a dose-response association between alcohol consumption and AMD or the association between moderate alcohol consumption and AMD. CONCLUSIONS: Heavy alcohol consumption (more than three standard drinks per day) is associated with an increased risk of early AMD. Although this association seems to be independent of smoking, residual confounding effects from smoking cannot be excluded completely.     

Risk factors evaluation in age- related macular degeneration

Age-related macular degeneration (AMD) is a leading cause of irreversible loss of central vision in developing countries. Study of risk factors seems to be more significant because of the lack of effective treatment. Exact recognition especially of modifiable risk factors of AMD development could increase prevention and decrease development and progression. The aim of our study was to evaluate selected modifiable and non-modifiable risk factors of AMD. The examination included 44 AMD patients and 30 healthy subjects in control group. In both groups age, sex, eye color, smoking, UV exposition, blood pressure, cholesterol level, type of diet, family history of AMD and cataract surgeries in anamnesis, were defined. The most significant risk factors of AMD development, in presented study were female gender and UV exposition. They increased a risk accordingly 1.55 and 3 times. Iris color and low vitamin and high fat intake in diet were also essential. There was no dependence on approved risk factor such smoking and AMD appearance.     

Ätiologie und Pathogenese der altersabhängigen Makuladegeneration

Age-related macular degeneration (AMD) is the most common cause of blindness in Germany. Due to the demographic development a further increase of affected patients is to be expected. Improved understanding of AMD pathogenesis resulted from the molecular biological approaches in recent years and showed an association of genetic factors with AMD. The complement factor H gene and the second high-risk locus ARMS2 in particular were found to contribute a significant risk for development of the disease. Ageing and environmental factors, such as smoking, modulate the individual genetic risk profile. A detailed understanding of the complex AMD pathogenesis is also relevant in ophthalmological practice to understand new treatment strategies. In this review we aim to give an overview of the interplay of ageing, external environmental factors and genetic risk variants leading to AMD.     

Mitochondrial dysfunction in retinal diseases

The mitochondrion is a vital intracellular organelle for retinal cell function and survival. There is growing confirmation to support an association between mitochondrial dysfunction and a number of retinal degenerations. Investigations have also unveiled mitochondrial genomic instability as one of the contributing factors for age-related retinal pathophysiology. This review highlights the role of mitochondrial dysfunction originating from oxidative stress in the etiology of retinal diseases including diabetic retinopathy, glaucoma and age-related macular degeneration (AMD). Moreover, mitochondrial DNA (mtDNA) damage associated with AMD due to susceptibility of mtDNA to oxidative damage and failure of mtDNA repair pathways is also highlighted in this review. The susceptibility of neural retina and retinal pigment epithelium (RPE) mitochondria to oxidative damage with ageing appears to be a major factor in retinal degeneration. It thus appears that the mitochondrion is a weak link in the antioxidant defenses of retinal cells. In addition, failure of mtDNA repair pathways can also specifically contribute towards pathogenesis of AMD. This review will further summarize the prospective role of mitochondria targeting therapeutic agents for the treatment of retinal disease. Mitochondria based drug targeting to diminish oxidative stress or promote repair of mtDNA damage may offer potential alternatives for the treatment of various retinal degenerative diseases.     

Chronic Kidney Disease,Early Age-related Macular Degeneration,and Peripheral Retinal Drusen

Purpose: To evaluate the association between chronic kidney disease (CKD) and early age-related macular degeneration (AMD) and peripheral retinal drusen in Korean adults 50 years and older.

Methods: This study included 3008 participants aged 50–87 years. Early AMD was assessed from retinal photographs based on modified Wisconsin AMD grading system and peripheral retinal drusen were assessed with a standardized examination. We defined CKD as estimated glomerular filtration rate of 60mL/min/1.73m² and below according to the Modification of Diet in Renal Disease equation. Logistic regression was used to examine the association between early AMD, peripheral retinal drusen, and CKD.

Results: There were 88 subjects with early AMD and 42 subjects with peripheral retinal drusen. After adjusting for age, gender, body mass index, smoking status, hypertension, and diabetes mellitus, a significant association was found between CKD and peripheral retinal drusen as well as early AMD. Subjects with CKD were more likely to have early AMD (OR, 1.68; 95% CI, 1.04–2.72) and peripheral retinal drusen (OR, 2.01; 95% CI, 1.02–3.99) than those without CKD.

Conclusions: CKD was associated with peripheral retinal drusen as well as early AMD in Korean adults 50 years and older.     

Cigarette smoke-related oxidants and the development of sub-RPE deposits in an experimental animal model of dry AMD

PURPOSE: Oxidative injury to the retinal pigment epithelium (RPE) has been proposed to be an important injury stimulus relevant to the accumulation of subretinal deposits in age-related macular degeneration (AMD). Cigarette smoking is a major risk factor for AMD, and cigarette smoke-related tar contains high concentrations of a potent oxidant, hydroquinone (HQ). This study was an investigation of the effects of cigarette smoke (CS) and HQ in the development of sub-RPE deposits in an experimental mouse model. METHODS: Sixteen-month-old C57BL/6 female mice were fed a high-fat diet (HFD) for 4.5 months. Mice were divided into two major experimental groups, one to examine the effects of cigarette smoke and one to study the effects of a defined cigarette smoke component such as HQ. In the first group, mice eyes were exposed to blue-green light (positive controls) or to whole cigarette smoke. A third group with no intervention served as the negative control. In the second experimental group, animals received a purified diet with HQ (0.8%) with low or high fat content for 4.5 months. Mice in both groups were euthanatized at 4.5 months and eyes processed for transmission electron microscopy. RESULTS: As previously demonstrated by our laboratory and others, most mice fed an HFD without other oxidant exposure demonstrated normal morphology or, in a few cases, small nodular basal laminar deposits. Eyes of mice exposed to whole cigarette smoke or to HQ in the food demonstrated a variable degree of basal laminar deposits and diffusely thickened Bruch's membrane. The choriocapillaris endothelium was variably hypertrophic. CONCLUSIONS: 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.     

Estrogen receptor alpha gene polymorphisms associated with incident aging macula disorder

PURPOSE: It has been suggested that early menopause increases the risk of aging-macula disorder (AMD), the major cause of incurable blindness with a dry and wet late subtype, and that exposure to endogenous or postmenopausal exogenous estrogens reduces this risk. This study was undertaken to investigate whether genetic variations in the estrogen receptor alpha (ESR1) gene are associated with incident AMD. METHODS: In the Rotterdam Study, a prospective population-based cohort study of participants aged 55 years and older, associations between ESR1 PvuII-XbaI haplotypes and incident early or late AMD were studied in 4571 participants after a mean follow-up time of 7.7 years. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs), with adjustment for the most common confounders. RESULTS: ESR1 PvuII-XbaI haplotype 1 was a risk factor for late AMD. Persons with two copies of haplotype 1 were at 3.20 (95% CI, 1.47-6.99) times higher risk for late AMD than noncarriers of haplotype 1, after adjustment for age and sex. This increase was more pronounced for wet AMD (hazard ratio [HR] 4.29; 95% CI, 1.47-12.49) after adjustment for age, sex, smoking, and complement factor H genotype. Correction for additional confounders, including age at menopause, use of hormone replacement therapy, blood pressure, and body mass index did not essentially alter the findings. CONCLUSIONS: Persons with one or two copies of ESR1 PvuII-XbaI haplotype 1 have an increased risk of late AMD, especially of the wet form.     

Smoking, alcohol intake, estrogen use, and age-related macular degeneration in Latinos: the Los Angeles Latino Eye Study

PURPOSE: To assess the association between smoking, alcohol intake, estrogen use, and both early age-related macular degeneration (AMD) (soft indistinct drusen, retinal pigment abnormalities) and advanced AMD (exudative AMD, geographic atrophy) in the Latino community. DESIGN: Population-based, cross-sectional study. METHODS: Complete ophthalmic examination included stereoscopic macular photographs graded with a modified Wisconsin Age-related Maculopathy Grading System. A history of smoking, alcohol intake, and exogenous estrogen use was obtained by interview. Logistic regression was performed, and odds ratios (OR) were calculated with each AMD lesion as a dependent variable. RESULTS: There were 5875 participants (92.4%) with gradable photographs. Having ever smoked was associated with a higher risk of having advanced AMD (OR, 2.4). Heavy consumption of alcohol (>5 drinks per session) was significantly associated with a greater risk of having exudative AMD (OR, 5.8) and geographic atrophy (OR, 12.7) Beer drinking was associated with a higher risk of having advanced AMD (OR, 2.9), whereas wine drinking appeared to be protective for increased retinal pigment (OR, 0.7). Exogenous estrogen use also appeared to be protective from soft indistinct drusen (OR, 0.5) and increased retinal pigment (OR, 0.6), but power was limited in the assessment of its association with advanced AMD. CONCLUSION: Smoking and heavy alcohol consumption, particularly beer, was associated with a greater risk of having advanced AMD; exogenous estrogen use appeared to have a weak protective effect in Latino participants. Similar modifiable risk factors have been identified previously in non-Hispanic white patients, which suggests that common pathogenic mechanisms may be associated with AMD in persons of different ethnicities.     

南充市顺庆区中老年年龄相关性黄斑变性患病率及相关因素分析

目的：了解南充市顺庆区50岁及以上人群年龄相关性黄斑变性(AMD)患病率并探讨影响AMD的相关因素。

方法：以人群为基础的流行病学调查。2013-05/10,采用分层整群随机抽样方法,抽取四川省南充市顺庆区50岁及以上人群共2 242人。调查内容包括一般信息登记,体格检查,实验室检查,眼科检查。AMD的诊断标准采用AMD国际临床分级系统。采用SPSS 13.0统计学软件对结果进行分析。

结果：本研究调查实际有2 097人接受全程检查,受检率为93.53%。检出AMD患者207例(283眼),总患病率为9.87%,标准化后AMD的患病率为9.73%。早期和晚期AMD患病率分别为9.25%和0.62%,其中渗出性AMD患病率为0.14%。50～59、60～69、70～79及≥80岁组的AMD患病率分别为6.38%、9.27%、14.69%、17.39%。AMD导致双侧盲及低视力患病率分别为0.48%和1.45%。晚期AMD患眼视力明显低于早期AMD患眼视力。与AMD相关的影响因素有8个,年龄、收缩压、吸烟、阳光暴露、糖尿病史、白内障手术、血清总胆固醇是AMD发生的危险因素,受教育程度是保护因素。

结论：南充市顺庆区50岁及以上人群AMD患病率为9.87%,AMD患病率随着年龄的增加呈明显增长的趋势; 晚期AMD严重影响视力; AMD致病危险因素包括年龄、收缩压、吸烟、阳光暴露、糖尿病史、白内障手术、血清总胆固醇,保护因素为受教育程度。     

Smoking and age-related macular degeneration: a review of association

PURPOSE: Age-related macular degeneration (AMD) is the leading cause of severe and irreversible vision loss in the Western world. As there is no effective treatment for all types of AMD, identifying modifiable risk factors is of great importance. This review evaluates the epidemiological evidence associating smoking with AMD. METHODS: Systematic review of published epidemiological studies evaluated against established criteria for evidence of a causal relationship. RESULTS: In total, 17 studies (cross-sectional studies, prospective cohort studies, and case-control studies) were included in the review. A total of 13 studies found a statistically significant association between smoking and AMD with increased risk of AMD of two- to three-fold in current-smokers compared with never-smokers. Five studies found no association between smoking and AMD. There was also evidence of dose-response, a temporal relationship and reversibility of effect. CONCLUSION: The literature review confirmed a strong association between current smoking and AMD, which fulfilled established causality criteria. Cigarette smoking is likely to have toxic effects on the retina. In spite of the strength of this evidence, there appears to be a lack of awareness about the risks of developing eye disease from smoking among both healthcare professionals and the general public.