AMD Articles 2

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Urinary cadmium and age-related macular degeneration

         (Erie, Good et al. 2007) Download

PURPOSE: To evaluate the association between urinary and blood cadmium (Cd) levels with age-related macular degeneration (AMD). DESIGN: Prospective case-control study. METHODS: In 53 participants older than 60 years with AMD in both eyes and in 53 age-matched (+/- 3 years) controls without AMD, Cd levels were measured in blood and urine specimens (with and without creatinine adjustment) by using inductively coupled plasma-mass spectrometry. Data on age, gender, smoking status, and family history were obtained. By using color stereoscopic fundus photographs, the degree of AMD was graded using the Age-Related Eye Disease Study's 4-stage AMD severity scale. The inclusion criterion for AMD cases was a photographic severity level of two to four in both eyes. Median blood and urine Cd and median urine Cd/creatinine concentrations in cases and controls were compared by using the rank-sum test, stratifying for smoking status. RESULTS: Current and former smokers with AMD had median urine Cd/creatinine levels (1.18 microg/g; range, 0.84 to 1.44 microg/g) that were 97% higher than smokers without AMD (0.60 microg/g; range, 0.49 to 0.90 microg/g; P = .02), 111% higher than never smokers with AMD (0.56 microg/g; range, 0.40 to 0.80 microg/g; P < .001) and 107% higher than never smokers without AMD (0.57 microg/g; 0.40 to 0.65 microg/g; P < .001). Blood Cd levels, indicative of short-term exposure levels, were not associated with AMD (P >/= .06). CONCLUSIONS: A higher urinary Cd level, which reflects the total body burden of Cd, was associated with AMD in smokers. Accumulated Cd exposure may be important in the development of smoking-related AMD.

Excess lead in the neural retina in age-related macular degeneration

            (Erie, Good et al. 2009) Download

PURPOSE: To measure lead and cadmium in retinal tissues of human donor eyes with and without age-related macular degeneration (AMD). DESIGN: Laboratory investigation. METHODS: Lead and cadmium concentrations in retinal tissues (neural retina and retinal pigment epithelium [RPE]-choroid complex) in 25 subjects with AMD (50 donor eyes) and 36 normal subjects (72 donor eyes) were determined by using inductively coupled plasma-mass spectrometry. Severity of AMD was graded by using color fundus photographs and the Minnesota Grading System. Differences in metal concentrations were compared by using Wilcoxon rank-sum tests. RESULTS: The neural retinas of subjects with AMD had increased lead concentrations (median, 12.0 ng/g; 25% to 75% interquartile range, 8 to 18 ng/g; n = 25) compared with normal subjects (median, 8.0 ng/g; 25% to 75% interquartile range, 0 to 11 ng/g; P = .04; n = 36). There was no difference in lead concentration in the RPE-choroid complex between subjects with AMD (median, 198 ng/g; 25% to 75% interquartile range, 87 to 381 ng/g) and normal subjects (median, 172 ng/g; 25% to 75% interquartile range, 100 to 288 ng/g; P = .25). Cadmium concentration in the neural retina (median, 0.9 microg/g; 25% to 75% interquartile range, 0.7 to 1.8 microg/g) and RPE-choroid complex (median, 2.2 microg/g; 25% to 75% interquartile range, 1.8 to 3.7 microg/g) in subjects with AMD was not different from concentrations in the neural retina (median, 0.9 microg/g; 25% to 75% interquartile range, 0.7 to 1.4 microg/g; P = .32) and RPE-choroid complex (median, 1.5 microg/g; 25% to 75% interquartile range, 0.9 to 2.5 microg/g; P = .12) of normal subjects. CONCLUSIONS: AMD is associated with excess lead in the neural retina, and this relationship suggests that metal homeostasis in AMD eyes is different from normal.

Age-Related Macular Degeneration (AMD): Alzheimer's Disease in the Eye?

            (Kaarniranta, Salminen et al. 2011) Download

Age-related macular degeneration (AMD) is a late-onset, neurodegenerative retinal disease that shares several clinical and pathological features with Alzheimer's disease (AD), including stress stimuli such as oxidative stress and inflammation. In both diseases, the detrimental intra- and extracellular deposits have many similarities. Aging, hypercholesterolaemia, hypertension, obesity, arteriosclerosis, and smoking are risk factors to develop AMD and AD. Cellular aging processes have similar organelle and signaling association in the retina and brain tissues. However, it seems that these diseases have a different genetic background. In this review, differences and similarities of AMD and AD are thoroughly discussed.

Mitochondrial DNA damage as a potential mechanism for age-related macular degeneration

            (Karunadharma, Nordgaard et al. 2010) Download

PURPOSE: Increasing evidence suggests a central role for mitochondrial (mt) dysfunction in age-related macular degeneration (AMD). Previous proteomic data from the retinal pigment epithelium (RPE) revealed significant changes to mt proteins, suggesting potential functional defects and damage to mitochondrial DNA (mtDNA) with AMD progression. The present study tests the hypothesis that mtDNA damage increases with aging and AMD. METHODS: Genomic DNA was isolated from the macular region of human donor RPE graded for stages of AMD (Minnesota Grading System [MGS] 1-4). Region-specific mtDNA damage with normal aging was evaluated in 45 control subjects (ages 34-88 years, MGS 1) and AMD-associated damage in diseased subjects (n = 46), compared with that in age-matched control subjects (n = 26). Lesions per 10 kb per genome in the mtDNA and nuclear DNA were measured with long-extension polymerase chain reaction (LX PCR). The level of deleted mtDNA in each donor was measured with quantitative real-time PCR (qPCR). RESULTS: With aging, an increase in mtDNA damage was observed only in the common deletion region of the mt genome. In contrast, with AMD, mtDNA lesions increased significantly in all regions of the mt genome beyond levels found in age-matched control subjects. mtDNA accumulated more lesions than did two nuclear genes, with total damage of the mt genome estimated to be eight times higher. CONCLUSIONS: Collectively, the data indicate that mtDNA is preferentially damaged with AMD progression. These results suggest a potential link between mt dysfunction due to increased mtDNA lesions and AMD.

Nutritional supplements for age-related macular degeneration

            (Krishnadev, Meleth et al. 2010) Download

PURPOSE OF REVIEW: Age-related macular degeneration (AMD), a leading cause of visual loss in older adults, has limited therapeutic options. This review describes the current literature on the role of nutritional supplementation in primary and secondary prevention of AMD. RECENT FINDINGS: Many observational studies have explored the association between diet, nutrient intake, and AMD. In particular, high dietary intakes of omega-3 fatty acids, and macular xanthophylls lutein and zeaxanthin have been associated with a lower risk of prevalent and incident AMD. However, the Age-Related Eye Disease study (AREDS) is the only large-scale randomized controlled clinical trial to show a 25% beneficial effect of nutritional supplementation in reducing the risk progression to advanced AMD in patients with intermediate AMD or with advanced AMD in one eye at 5 years of follow-up. On the basis of the results of AREDS, these patients are recommended to take AREDS formulation of vitamins C, E, beta-carotene, and zinc with copper. SUMMARY: At the present time, there is insufficient evidence in the literature to recommend routine nutritional supplementation in healthy adults for primary prevention of AMD. However, patients with intermediate risk of AMD or advanced AMD in one eye should consider taking AREDS-type supplements. Observational studies have also suggested benefit from increased dietary intake of macular xanthophylls and omega-3 fatty acids. These are currently being evaluated prospectively in a randomized controlled clinical trial, the AREDS2.

Long-chain and very long-chain polyunsaturated fatty acids in ocular aging and age-related macular degeneration

            (Liu, Chang et al. 2010) Download

Retinal long-chain PUFAs (LC-PUFAs, C(12)-C(22)) play important roles in normal human retinal function and visual development, and some epidemiological studies of LC-PUFA intake suggest a protective role against the incidence of advanced age-related macular degeneration (AMD). On the other hand, retinal very long-chain PUFAs (VLC-PUFAs, C(n>22)) have received much less attention since their identification decades ago, due to their minor abundance and more difficult assays, but recent discoveries that defects in VLC-PUFA synthetic enzymes are associated with rare forms of inherited macular degenerations have refocused attention on their potential roles in retinal health and disease. We thus developed improved GC-MS methods to detect LC-PUFAs and VLC-PUFAs, and we then applied them to the study of their changes in ocular aging and AMD. With ocular aging, some VLC-PUFAs in retina and retinal pigment epithelium (RPE)/choroid peaked in middle age. Compared with age-matched normal donors, docosahexaenoic acid, adrenic acid, and some VLC-PUFAs in AMD retina and RPE/choroid were significantly decreased, whereas the ratio of n-6/n-3 PUFAs was significantly increased. All these findings suggest that deficiency of LC-PUFAs and VLC-PUFAs, and/or an imbalance of n-6/n-3 PUFAs, may be involved in AMD pathology.

Aspirin, iron loss, and age-related macular degeneration

            (Mascitelli, Pezzetta et al. 2010) Download

Potential role of uric acid in the molecular pathogenesis of age-related macular degeneration.

         (Mehryar, Farvardin et al. 2006) Download

Age-related macular degeneration (ARMD) is the foremost cause of blindness among the elderly population in industrialised countries. Currently, there is no effective treatment for the majority of patients. To develop new and effective modes of therapy, understanding of the molecular basis of the disease is mandatory. Many age-related pathologies have been attributed to cumulative oxidative damage caused by reactive oxygen intermediates. There is growing evidence that uric acid has antioxidant properties and it is a naturally occurring antioxidant. Based on antioxidant role in pathogenesis of ARMD and antioxidant properties of uric acid we conclude that altered uric acid metabolism could play a role in ARMD damage and pathogenesis. Future research needs to evaluate uric acid metabolism in ARMD patients.

Autoimmunity in retinal degeneration: autoimmune retinopathy and age-related macular degeneration

            (Morohoshi, Goodwin et al. 2009) Download

Autoantibody production is associated with a variety of ocular disorders, including autoimmune retinopathy (AIR) and age-related macular degeneration (AMD). A breakdown of immunologic tolerance (ocular immune privilege), including the blood-retinal barrier, anti-immune and anti-inflammatory proteins, and anterior chamber-associated immune deviation may play important roles in these disorders. Although the exact triggers for ocular autoimmunity are unknown, autoimmune targeting of retinal tissue is clearly associated with and may contribute to the pathogenesis of both AIR and AMD. Autoantibody production has long been associated with AIR, a collection of disorders that includes cancer-associated retinopathy, melanoma-associated retinopathy and non-paraneoplastic autoimmune retinopathy. A growing body of evidence indicates that AMD pathogenesis, too, involves ocular inflammation and autoimmunity. Identification and quantification of autoantibodies produced in patients with AIR and AMD may assist with diagnosis, prognosis, and choice of treatments. Animal models that allow investigation of ocular autoimmunity will also be needed to better understand the disease processes and to develop novel therapies. In this review we discuss ocular immune privilege and potential mechanisms of autoimmunity in the eye. We describe how autoimmunity relates to the pathogenesis of AIR and AMD. We explain how the antigen microarray technique is used to detect autoantibodies in patient serum samples, and discuss how current animal models for AMD can be used to investigate autoimmune pathogenesis. Finally, we outline unanswered questions and exciting areas of future study related to autoimmune retinal degeneration.

Associations between chronic kidney disease and age-related macular degeneration

            (Nitsch, Evans et al. 2009) Download

PURPOSE: Age-related macular degeneration (AMD) and renal impairment are both associated with cardiovascular risk factors and with alterations in the complement pathways. There are few data on the association of AMD with chronic kidney disease. METHODS: People who were visually impaired (binocular acuity < 6/18) due to AMD (ascertained from review of medical notes; n = 516) were compared to people with normal vision (6/6 or better; n = 2755). Cases with AMD and controls derive from a population-based cross-sectional study of people aged 75 years and over registered with 49 family practices in Britain. Glomerular filtration rate (eGFR) was estimated with the Modification of Diet in Renal Disease formula and proteinuria assessed by dipsticks. RESULTS: After adjusting for a wide range of confounding factors, the presence of proteinuria was positively associated with AMD among men (odds ratio (OR) 2.06, 95% confidence interval (CI) 1.05, 4.04) but not in women (OR 0.62 95%CI 0.36,1.08). Among men, eGFR < 45 ml/min/1.73 m(2) was associated with AMD but not after adjusting for proteinuria. This was not observed for women. Both proteinuria and eGFR showed different associations with AMD by sex (p-values for interaction < 0.05). CONCLUSIONS: Proteinuria appears to be a risk factor for AMD among men but not among women, possibly due to measurement errors in detecting proteinuria in women.

Potential of melatonin to treat or prevent age-related macular degeneration through stimulation of telomerase activity

            (Rastmanesh 2011) Download

Melatonin may play a causal role in the occurrence of age-related macular degeneration (AMD). Replicative capacity and response to injury in the retinal pigment epithelium (RPE) is compromised during aging. Prevention of telomere shortening by antioxidants may be a useful approach for reducing the cumulative effects of oxidative stress in RPE cells. Melatonin, a well known antioxidant, which acts advantageously as an amphiphilic agent, may benefit AMD patients more than commonly used lipophilic or hydrophilic antioxidants. It also may act through mechanisms other than antioxidant mechanisms because melatonin has receptors localized in the RPE, which act locally as a neurohormone and/or neuromodulator. Results of a clinical trial showed that 3mg melatonin given orally each night at bedtime for 3 months to AMD patients reduced pathologic macular changes. I hypothesize that melatonin exerts additional benefit through down-regulating hTERT (catalytic subunit if telomerase) expression and stimulated telomerase activity in RPE, which subsequently helps to prevent or treat AMD. I suggest that melatonin therapy as pharmacologic agents and/or melatonin-rich foods, especially in AMD patients with measured low serum melatonin levels or high risk patients would be possibly an alternative approach to prevent and/or treat AMD. I suggest that melatonin has potential to prevent telomere shortening in RPE, while not precluding other mechanisms, namely antioxidative properties and/or restoration of inner blood-retina barrier (iBRB) integrity, reduced vascular endothelial growth factor (VEGF) and nitric oxide (NO) levels as well as leakage of horseradish peroxidase (HRP), inhibiting hypoxia-inducible factor-1 alpha (HIF-1 alpha) stabilization under hypoxia.

Dietary n-3 PUFA vascular targeting and the prevention of tumor growth and age-related macular degeneration

            (Serini, Piccioni et al. 2009) Download

The protective role of dietary n-3 polyunsaturated fatty acids (PUFAs) against cardiovascular diseases has been partly related to their ability to modulate the risk condition known as "endothelial dysfunction", by reverting the endothelial alterations associated to it (reduced vascular reactivity, the proinflammatory state, and the prothrombotic properties). Moreover, vasculature represents the target for inhibition of pathologic neo-angiogenesis by n-3 PUFAs. This effect is believed to contribute to the beneficial action of these fatty acids against disorders which recognize neovascularization as a crucial pathogenetic step for their development, such as cancer and age-related macular degeneration (AMD). Many epidemiological studies have been conducted to evaluate the association between the intake of these fatty acids and the risk of developing cancer or AMD, even though contrasting and not definitive results have been obtained. Conversely, plenty of preclinical and in vitro experimental studies have provided evidence for the anti-angiogenic effects of n-3 PUFAs, mainly studying neo-angiogenesis in general (using normal endothelial cells in vitro) or as a step of cancer growth. The main aim of this review is to critically review the current evidence for the inhibition of the neo-angiogenic process exerted by n-3 PUFAs in cancer and AMD, and to identify possible molecular mechanisms that might contribute to their beneficial effects.

Macular degeneration: A possible biochemical mechanism

            (Soloway, Curley et al. 2011) Download

The possible role of labile endogenous metabolites in the cause of various chronic debilitating diseases such as macular degeneration has not been adequately explored. In the metabolism of the various retinoids, namely retinal (vitamin A aldehyde), retinol (vitamin A alcohol) and retinoic acid, each has the potential for generating labile intermediates, such as their corresponding 5,6-epoxides by the action of various cytochrome P(450)s. Such retinoid epoxides may well have the capacity for acting as toxins upon the neurons in the macula unless they are rapidly hydrolyzed by epoxide hydrolases. Since the cytochrome P(450)s responsible for epoxide formation and the various epoxide hydrolases involved in their hydrolysis are determined genetically, this may serve to explain a genetic component being involved in the causation of age-related macular degeneration.

Serum uric acid levels and its association with age-related macular degeneration (ARMD)

            (Subramani, Khor et al. 2011) Download

To investigate the possible association between serum uric acid levels, serum C-Reactive Protein (CRP), and age-related macular degeneration (ARMD). A total 232 patients of the eye department at Hospital Tuanku Ja'afar, Negeri Sembilan, Malaysia were recruited over 9 weeks. Participants were divided into ARMD (Non-Neovascular ARMD, and Neovascular ARMD) and control groups. 107 participants with non-neovascular ARMD, 6 with neovascular ARMD, and 119 controls participated in the study. The control patients had a similar average Serum Uric Acid level to the average of all patients with ARMD (P = 0.617). Control group: mean 299.19 micromol/l +/- std dev. 89.847 micromol/l. ARMD group: mean 302.53 micromol/l +/- std dev. 80.794 micromol/l. The average serum uric acid levels were higher in patients with neovascular ARMD (median = 397 mean +/- std dev = 389.67 +/- 38 micromol/l) than in the non-neovascular ARMD group (288.5 micromol/l, 297.86 +/- 80.26 micromol/l), and control group (295.5 micromol/l, 299.19 +/- 89.95 micromol/l). Comparing the standardised serum uric acid levels in the control group (Median = 0.5) against the two ARMD groups separately, there was no significant difference to the non-neovascular group (P = 0.448) but there was a difference significant to the neovascular ARMD group (P = 0.044). The neovascular and non-neovascular ARMD groups had median CRP value of 0.25 mg/l and were not significantly different. There is no association between serum uric acid levels and ARMD as a whole. There is potentially an association between serum uric acid and neovascular ARMD, an association needs to be established further. There is no association between serum CRP and ARMD.

DNA damage and repair in age-related macular degeneration

            (Szaflik, Janik-Papis et al. 2009) Download

Age-related macular degeneration (AMD) is a retinal degenerative disease that is the main cause of vision loss in individuals over the age of 55 in the Western world. Clinically relevant AMD results from damage to the retinal pigment epithelial (RPE) cells thought to be mainly caused by oxidative stress. The stress also affects the DNA of RPE cells, which promotes genome instability in these cells. These effects may coincide with the decrease in the efficacy of DNA repair with age. Therefore individuals with DNA repair impaired more than average for a given age may be more susceptible to AMD if oxidative stress affects their RPE cells. This may be helpful in AMD risk assessment. In the present work we determined the level of basal (measured in the alkaline comet assay) endogenous and endogenous oxidative DNA damage, the susceptibility to exogenous mutagens and the efficacy of DNA repair in lymphocytes of 100 AMD patients and 110 age-matched individuals without visual disturbances. The cells taken from AMD patients displayed a higher extent of basal endogenous DNA damage without differences between patients of dry and wet forms of the disease. DNA double-strand breaks did not contribute to the observed DNA damage as checked by the neutral comet assay and pulsed field gel electrophoresis. The extent of oxidative modification to DNA bases was greater in AMD patients than in the controls, as probed by DNA repair enzymes NTH1 and Fpg. Lymphocytes from AMD patients displayed a higher sensitivity to hydrogen peroxide and UV radiation and repaired lesions induced by these factors less effectively than the cells from the control individuals. We postulate that the impaired efficacy of DNA repair may combine with enhanced sensitivity of RPE cells to blue and UV lights, contributing to the pathogenesis of AMD.

Oxidative macromolecular damage in age-related macular degeneration

            (Totan, Yagci et al. 2009) Download

PURPOSE: To evaluate oxidative damage to the macromolecules, including protein, lipid, and DNA, in association with total oxidation status (TOS), total antioxidant capacity (TAC) in patients with exudative age-related macular degeneration (AMD). MATERIALS AND METHODS: Serum levels of malondialdehyde (MDA) as an index of lipid peroxidation, protein carbonyl (PC) as a marker of protein oxidation, 8-hydroxy-29-deoxyguanosine (8-OHdG) as an indicator of oxidative DNA damage along with TOS, TAC were measured by specific methods in 47 patients with exudative AMD and 25 age- and sex-matched healthy subjects. RESULTS: Significantly higher MDA, PC, 8-OHdG, TOS, and lower TAC levels were detected in the serum of patients with exudative AMD compared with their controls (p < 0.001). CONCLUSION: The results indicate that an imbalance between TOS and TAC leads to not only increased lipid damage, but also protein and DNA damage. These first reported results suggest that protein and DNA damage might also play a role in the pathogenesis of AMD.

Iron toxicity as a potential factor in AMD

            (Wong, Richa et al. 2007) Download

While it has been known for years that iron overload is associated with retinal degeneration in the context of ocular siderosis, intraocular hemorrhage, and the hereditary diseases aceruloplasminemia and pantothenate kinase associated neurodegeneration, recent evidence suggests that age-related macular degeneration (AMD) may also be exacerbated by retinal iron overload. In the retina, iron is necessary for normal cellular function. Iron overload, however, can cause retinal toxicity through the generation of oxygen free radicals. Histopathology of eyes with macular degeneration has shown elevated levels of iron in the retinal pigment epithelium, Bruch membrane, and within drusen, some of which was chelatable in vitro with deferoxamine. In this review, the authors summarize the evidence that iron overload may contribute to AMD pathogenesis. It is hoped that continued investigation of the role of iron and iron associated proteins in the retina will uncover clues to AMD pathogenesis and lead to new preventative or therapeutic options.

Pathway-based therapies for age-related macular degeneration: an integrated survey of emerging treatment alternatives

            (Zarbin and Rosenfeld 2010) Download

PURPOSE: To review treatments under development for age-related macular degeneration (AMD) in the context of current knowledge of AMD pathogenesis. METHODS: Review of the scientific literature published in English. RESULTS: Steps in AMD pathogenesis that appear to be good targets for drug development include 1) oxidative damage; 2) lipofuscin accumulation; 3) chronic inflammation; 4) mutations in the complement pathway; and 5) noncomplement mutations that influence chronic inflammation and/or oxidative damage (e.g., mitochondria and extracellular matrix structure). Steps in neovascularization that can be targeted for drug development and combination therapy include 1) angiogenic factor production; 2) factor release; 3) binding of factors to extracellular receptors (and activation of intracellular signaling after receptor binding); 4) endothelial cell activation (and basement membrane degradation); 5) endothelial cell proliferation; 6) directed endothelial cell migration; 7) extracellular matrix remodeling; 8) tube formation; and 9) vascular stabilization. CONCLUSION: The era of pathway-based therapy for the early and late stages of AMD has begun. At each step in the pathway, a new treatment could be developed, but complete inhibition of disease progression will likely require a combination of the various treatments. Combination therapy will likely supplant monotherapy as the treatment of choice because the clinical benefits (visual acuity and frequency of treatment) will likely be superior to monotherapy in preventing the late-stage complications of AMD.


Erie, J. C., J. A. Good, et al. (2009). "Excess lead in the neural retina in age-related macular degeneration." Am J Ophthalmol 148(6): 890-4.

Erie, J. C., J. A. Good, et al. (2007). "Urinary cadmium and age-related macular degeneration." Am J Ophthalmol 144(3): 414-418.

Kaarniranta, K., A. Salminen, et al. (2011). "Age-Related Macular Degeneration (AMD): Alzheimer's Disease in the Eye?" J Alzheimers Dis.

Karunadharma, P. P., C. L. Nordgaard, et al. (2010). "Mitochondrial DNA damage as a potential mechanism for age-related macular degeneration." Invest Ophthalmol Vis Sci 51(11): 5470-9.

Krishnadev, N., A. D. Meleth, et al. (2010). "Nutritional supplements for age-related macular degeneration." Curr Opin Ophthalmol.

Liu, A., J. Chang, et al. (2010). "Long-chain and very long-chain polyunsaturated fatty acids in ocular aging and age-related macular degeneration." J Lipid Res 51(11): 3217-29.

Mascitelli, L., F. Pezzetta, et al. (2010). "Aspirin, iron loss, and age-related macular degeneration." Med Hypotheses 74(4): 754-5.

Mehryar, M., M. Farvardin, et al. (2006). "Potential role of uric acid in the molecular pathogenesis of age-related macular degeneration." Med Hypotheses 66(4): 793-5.

Morohoshi, K., A. M. Goodwin, et al. (2009). "Autoimmunity in retinal degeneration: autoimmune retinopathy and age-related macular degeneration." J Autoimmun 33(3-4): 247-54.

Nitsch, D., J. Evans, et al. (2009). "Associations between chronic kidney disease and age-related macular degeneration." Ophthalmic Epidemiol 16(3): 181-6.

Rastmanesh, R. (2011). "Potential of melatonin to treat or prevent age-related macular degeneration through stimulation of telomerase activity." Med Hypotheses 76(1): 79-85.

Serini, S., E. Piccioni, et al. (2009). "Dietary n-3 PUFA vascular targeting and the prevention of tumor growth and age-related macular degeneration." Curr Med Chem 16(34): 4511-26.

Soloway, A. H., R. W. Curley, Jr., et al. (2011). "Macular degeneration: A possible biochemical mechanism." Med Hypotheses.

Subramani, S., S. E. Khor, et al. (2011). "Serum uric acid levels and its association with age-related macular degeneration (ARMD)." Med J Malaysia 65(1): 36-40.

Szaflik, J. P., K. Janik-Papis, et al. (2009). "DNA damage and repair in age-related macular degeneration." Mutat Res 669(1-2): 169-76.

Totan, Y., R. Yagci, et al. (2009). "Oxidative macromolecular damage in age-related macular degeneration." Curr Eye Res 34(12): 1089-93.

Wong, R. W., D. C. Richa, et al. (2007). "Iron toxicity as a potential factor in AMD." Retina 27(8): 997-1003.

Zarbin, M. A. and P. J. Rosenfeld (2010). "Pathway-based therapies for age-related macular degeneration: an integrated survey of emerging treatment alternatives." Retina 30(9): 1350-67.