Molecular pathology of age-related macular degeneration

In the paper

“We recently found no relationship between risk-conferring CFH variant and C. pneumoniae in 148 advanced AMD patients and 162 control subjects with the infection”

What the sources say

• Not checked yetcites Shen et al., 2008

In the paper

“although there is a positive association between AMD and C. pneumoniae infection (20% vs. 10% positive C. pneumoniae DNA detected in the blood of AMD patients compared with the controls) (Shen et al., 2008).”

What the sources say

• Not checked yetcites Shen et al., 2008

In the paper

“This previous study showed that CX3CR1 transcript and protein in the AMD maculae were undetectable or expressed at much lower levels than their SNP-type counterparts in the normal eyes.”

What the sources say

• Not checked yetcites Chan et al., 2005

In the paper

“we found lowered CX3CR1 expression in the macula compared with the perimacular retina of AMD eyes bearing T280M.”

What the sources say

• Not checked yetcites Chan et al., 2005

In the paper

“In normal eyes, macular cells from an individual bearing “at risk” allele T/M280 exhibited lower CX3CR1 transcript expression than an individual bearing “wild type or major” allele T280T.”

What the sources say

• Not checked yetcites Chan et al., 2005

In the paper

“In contrast, similar levels of CX3CR1 expression were detected in macular and perimacular regions of the normal subjects”

What the sources say

• Not checked yetcites Chan et al., 2005

In the paper

“Our data, including a population-based study (Wang et al., 2008), and data by Jakobsdottir and colleagues (Jakobsdottir et al., 2005) have both shown that the frequency of the ARMS2 risk allele is higher in patients with advanced AMD than in those with early or intermediate AMD.”

What the sources say

• Not checked yetcites Wang et al., 2008 source
• Not checked yetcites Jakobsdottir et al., 2005 source

In the paper

“Similar to findings by Feher and colleagues (Feher et al., 2006), we have also found a drastic decrease in normal mitochondria in the photoreceptors and RPE cells of the AMD eyes as compared to that of the normal age-control eyes (Fig. 5).”

What the sources say

• Not checked yetcites Feher et al., 2006 source

In the paper

“We have also found the association between ApoE112R (E4) and a decreased risk of AMD development, and the underlying mechanisms might involve differential regulation of both CCL2 and VEGF by the ApoE isoforms (Bojanowski et al., 2006).”

What the sources say

• Not checked yetcites Bojanowski et al., 2006 source

In the paper

“Compared to wild-type mice, Ccl2−/−/Cx3cr1−/− mice exhibited increased complement C3 and CD46.”

What the sources say

• Not checked yetcites Ross et al., 2008 source

In the paper

“These mice also exhibited ultrastructural signs of AMD such as accumulation of lipofuscin granules, as well as increased the N-retinylidene–N-retinylethanolamine (A2E) accumulation on biochemical analysis (Chan et al., 2008; Tuo et al., 2007).”

What the sources say

• Not checked yetcites Chan et al., 2008 source
• Not checked yetcites Tuo et al., 2007 source

In the paper

“Incubation of normal retinal sections with serum from Ccl2−/−/Cx3cr1−/− also demonstrated the presence of anti-retinal antibodies in the mouse model.”

What the sources say

• Not checked yetcites Ross et al., 2008 source

In the paper

“Analysis of C3d expression by immunoreactivity revealed that this increase was especially notable in Bruch’s membrane, drusen-like lesions, photoreceptors, RPE, and choroidal capillaries (Ross et al., 2008).”

What the sources say

• Not checked yetcites Ross et al., 2008 source

In the paper

“In contrast, minimal anti-retinal auto-antibody effect was noted in wild-type mice (Ross et al., 2008).”

What the sources say

• Not checked yetcites Ross et al., 2008 source

In the paper

“studies have shown that the most established factors are advanced age, cigarette smoking, diet, and race (Coleman et al., 2008; Jager et al., 2008).”

What the sources say

• Not checked yetcites Coleman et al., 2008
• Not checked yetcites Jager et al., 2008 source

In the paper

“The majority of studies have found a statistically significant association between smoking and development of AMD.”

What the sources say

• Not checked yetcites Klein, 2007 source

In the paper

“The AREDS demonstrated the efficacy of zinc-antioxidant supplements for preventing or delaying progression of early AMD to late AMD in patients who are at high risk (Bressler et al., 2003).”

What the sources say

• Not checked yetcites Bressler et al., 2003 source

In the paper

“A recent population-based cohort study in Australia (Tan et al., 2008) demonstrated that high dietary lutein and zeaxanthin intake reduced the risk of long-term incident AMD”

What the sources say

• Not checked yetcites Tan et al., 2008 source

In the paper

“The large drusen, bilateral drusen, and/or numerous drusen, are significant risk factors for development of late stage AMD.”

In the paper

“The presence of inflammation-related molecules in drusen suggests the possible involvement of the immune system in AMD pathogenesis (Hageman et al., 2001).”

What the sources say

• Not checked yetcites Hageman et al., 2001 source

In the paper

“high beta-carotene intake was associated with an increased risk of AMD.”

What the sources say

• Not checked yetcites Tan et al., 2008 source

In the paper

“Several family studies have shown that patients with a family history of AMD are at increased risk (Seddon et al., 2007; Smith and Mitchell, 1998).”

What the sources say

• Not checked yetcites Seddon et al., 2007 source
• Not checked yetcites Smith and Mitchell, 1998

In the paper

“Classically, subretinal, extracellular deposits composed of glycoproteins and lipids accumulate in Bruch’s membrane. These dumbbell shaped deposits are called drusen”

In the paper

“The earliest pathological changes are the appearance of basal laminar deposits (BlamD) and basal linear deposits (BlinL) (Green and Enger, 1993).”

What the sources say

• Not checked yetcites Green and Enger, 1993 source

In the paper

“The results showed that for AMD, the population-attributable risk (PAR) for a positive family history was 0.34.”

What the sources say

• Not checked yetcites Luo et al., 2008 source

In the paper

“However, the presence of large and many drusen in the macula signifies early AMD.”

In the paper

“In the earliest stage, they may be visible ophthalmoscopically, when their diameter exceeds 25 µm (Sarks et al., 1999)”

What the sources say

• Not checked yetcites Sarks et al., 1999 source

In the paper

“Many linkage and association studies have indicated that the most replicated signals reside on chromosome 1q25–31 and 10q26 (Fisher et al., 2005; Jakobsdottir et al., 2005; Klein et al., 1998; Majewski et al., 2003).”

What the sources say

• Not checked yetcites Fisher et al., 2005 source
• Not checked yetcites Jakobsdottir et al., 2005 source
• Not checked yetcites Klein et al., 1998 source

In the paper

“Complement components, other inflammatory molecules, lipids, lipoproteins B and E, and glycoproteins are common constituents of ocular drusen (Johnson et al., 2002).”

What the sources say

• Not checked yetcites Johnson et al., 2002 source

In the paper

“A number of studies have illustrated the presence of complement components and complement regulatory proteins in drusen and nearby RPE of AMD patients”

What the sources say

• Not checked yetcites Crabb et al., 2002 source
• Not checked yetcites Hageman et al., 1999 source
• Not checked yetcites Johnson et al., 2001 source

In the paper

“The primary clinical characteristic of late stage ‘dry’ AMD is the appearance of RPE atrophy, usually known as geographic atrophy.”

In the paper

“RAP, however, occurs much less frequently than the classical choroid-derived neovascular vessels.”

In the paper

“new vessels sprouting from the choroidal vessels, penetrating Bruch’s membrane and growing into the subretinal space are the classical descriptions of wet AMD (Green, 1999), which is most common”

What the sources say

• Not checked yetcites Green, 1999

In the paper

“AMD is no exception, as SNPs associated with inflammation, oxidative stress, angiogenesis, and other pathological processes have been linked to AMD.”

In the paper

“dysregulation of the cascade can result in complement overactivation-mediated damage to nearby healthy tissue.”

In the paper

“Immunohistochemical analyses have shown various molecular constituents, such as apolipoproteins B and E, different immunoglobulins, factor X, amyloid P component, amyloid β, complement C5 and C5b-9 terminal complexes, fibrinogen, vitronectin, and others, to be present in all phenotypes of hard and soft drusen”

What the sources say

• Not checked yetcites Anderson et al., 2004 source
• Not checked yetcites Johnson et al., 2000 source
• Not checked yetcites Mullins et al., 2000 source

In the paper

“Hyperpigmentary changes associated with compensatory RPE cell proliferation are frequently observed at the periphery of these hypopigmented areas (de Jong, 2006).”

What the sources say

• Not checked yetcites de Jong, 2006 source

In the paper

“Activation of the complement system generates a variety of pro-inflammatory responses, including the production of membrane-attack complexes (MAC) which lead to cell lysis, release of chemokines to mediate recruitment of inflammatory cells, and enhancement of capillary permeability (Walport, 2001a, b).”

What the sources say

• Not checked yetcites Walport, 2001a, b

In the paper

“These studies have been buttressed by genetic studies identifying inflammation-associated SNPs that modulate AMD risk.”

In the paper

“elevated serum level of CRP has been shown to be associated with AMD (Mold et al., 1999; Seddon et al., 2004).”

What the sources say

• Not checked yetcites Mold et al., 1999 source
• Not checked yetcites Seddon et al., 2004 source

In the paper

“CFH is a negative regulator of the complement system.”

In the paper

“Johnson and associates illustrated that individuals homozygous for the risk-conferring Y402H CFH variant have higher levels of CRP in the choroid compared to individuals homozygous for the “normal” Y402 variant.”

What the sources say

• Not checked yetcites Johnson et al., 2006 source

In the paper

“several studies have demonstrated that animal models with complement knockdown, either genetically or with pharmacological agents such as anti-complement antibodies, exhibit decreased CNV after laser injury”

What the sources say

• Not checked yetcites Patel and Chan, 2008

In the paper

“CFH is now widely accepted as an important AMD susceptibility gene, harboring variants and haplotypes associated with increased and reduced disease risk.”

In the paper

“CFH is identified in normal RPE and choroid (Klein et al., 2005).”

What the sources say

• Not checked yetcites Klein et al., 2005 source

In the paper

“The risk-conferring Y402H CFH variant (genotype CC) has also been reported to reduce the binding affinity to C-reactive protein (CRP), a pro-inflammatory molecule, as compared with the Y402Y variant (genotype TT).”

What the sources say

• Not checked yetcites Laine et al., 2007 source
• Not checked yetcites Skerka et al., 2007 source

In the paper

“A major AMD-associated SNP is the Y402H (tyrosine to histidine substitution at amino acid 402) variant of complement factor H (CFH) (Edwards et al., 2005; Hageman et al., 2005; Haines et al., 2005; Klein et al., 2005).”

What the sources say

• Not checked yetcites Edwards et al., 2005 source
• Not checked yetcites Hageman et al., 2005 source
• Not checked yetcites Haines et al., 2005 source

In the paper

“Moreover, C. pneumoniae has been found in AMD neovascular membranes (Kalayoglu et al., 2005).”

What the sources say

• Not checked yetcites Kalayoglu et al., 2005 source

In the paper

“a recent study demonstrating that the presence of the risk-conferring CFH variant and high C. pneumoniae antibody titer significantly increases AMD risk, well beyond the risk associated with possessing either risk factor alone (Baird et al., 2008).”

What the sources say

• Not checked yetcites Baird et al., 2008 source

In the paper

“These results support the notion that the association between CFH polymorphisms and AMD may involve CRP.”

In the paper

“The three SNPs at rs1061147, rs1061170, and rs380390 are in complete linkage disequilibrium (LD).”

In the paper

“In addition to the CFH Y402H (dbSNP ID: rs1061170) SNP, 5 other CFH variants (rs3753394, rs800292, rs1061147, rs1061170, rs380390, and rs1329428) have been reported in AMD association studies.”

In the paper

“The particular SNPs associated with AMD, however, depend upon the study and the study population.”

In the paper

“Among them, the rs1061170 (Y402H) was the only SNP that leads to a non-synonymous amino acid change.”

In the paper

“In contrast, there is no significant difference between the two phenotypes (YY and HH) in the amount of CFH protein in the RPE-choroid complex (Johnson et al., 2006).”

What the sources say

• Not checked yetcites Johnson et al., 2006 source

In the paper

“C. pneumoniae is a potent activator of the alternative complement system”

In the paper

“Thus, studies to date demonstrate an association between CFH and AMD.”

In the paper

“In the Chinese and Japanese populations, only three of these CFH SNPs–at rs1329428, rs800292 (I62V), and rs3753394, but not at rs1061170 (Y402H)–were associated with risk of exudative AMD (Chen et al., 2006; Okamoto et al., 2006).”

What the sources say

• Not checked yetcites Chen et al., 2006
• Not checked yetcites Okamoto et al., 2006

In the paper

“These SNPs have been reported to be major genetic factors for developing AMD in Caucasians (Edwards et al., 2005; Hageman et al., 2005; Haines et al., 2005; Klein et al., 2005; Tuo et al., 2006).”

What the sources say

• Not checked yetcites Edwards et al., 2005 source
• Not checked yetcites Hageman et al., 2005 source
• Not checked yetcites Haines et al., 2005 source

In the paper

“These results suggest that the zinc plus antioxidative treatment seems to have less impact on those with the high-risk CFH variant.”

In the paper

“the SNP variant rs2511989 located in the SERPING1 gene encoding the complement component 1 (C1) inhibitor was recently reported to occur less frequently in AMD cases than in control subjects (Ennis et al., 2008).”

What the sources say

• Not checked yetcites Ennis et al., 2008

In the paper

“Therefore, CFH may not be directly involved in the pathogenesis of C. pneumoniae infection-mediated AMD.”

In the paper

“the fast migrating allotype (C3F), has been reported to be strongly associated with AMD in a study from English and Scottish populations (Yates et al., 2007).”

What the sources say

• Not checked yetcites Yates et al., 2007 source

In the paper

“In a French study, homozygosity for the CX3CR1 T280M allele was also reported to be associated with AMD (Combadiere et al., 2007).”

What the sources say

• Not checked yetcites Combadiere et al., 2007 source

In the paper

“studies have demonstrated that at least one of the two variants associated with AMD—R32Q BF—leads to an impairment in the complement activating function of BF (Gold et al., 2006).”

What the sources say

• Not checked yetcites Gold et al., 2006 source

In the paper

“One study reported that C7 (rs2876849) is protective for AMD development in Caucasians (Dinu et al., 2007).”

What the sources say

• Not checked yetcites Dinu et al., 2007 source

In the paper

“In addition, a similar interaction was observed in the groups taking zinc versus those taking no zinc: zinc intake had a more dramatic protective effect in patients with non-risk alleles, compared with patients with risk alleles.”

What the sources say

• Not checked yetcites Klein et al., 2008a

In the paper

“This glomerulonephritis shares some similarities with AMD—namely, a role for uncontrolled alternative complement activation as well as the accumulation of complement-containing extracellular deposits.”

In the paper

“Thus, much like impaired CFH-mediated complement inhibition confers AMD risk, decreased complement activation by BF might serve to protect against AMD risk.”

In the paper

“The results show that only 10.5% of patients with the risk-conferring Y402H/Y402H phenotype demonstrated improved vision with treatment, compared with 53.7% of patients with the Y402Y/Y402Y and Y402Y/Y402H CFH variants (P = 0.004) (Brantley et al., 2008).”

What the sources say

• Not checked yetcites Brantley et al., 2008

In the paper

“Subsequent studies, for example by Despriet and Edwards, however, demonstrated no significant association of the D299G TLR4 SNP with AMD risk (Despriet et al., 2008; Edwards et al., 2008).”

What the sources say

• Not checked yetcites Despriet et al., 2008 source
• Not checked yetcites Edwards et al., 2008 source

In the paper

“SNPs in other pro-inflammatory chemokines including interleukin-1β (IL1β) C511T, interleukin-6 (IL6) C174G and the anti-inflammatory cytokine IL10 G1082A were analyzed and showed no significant association with AMD (Goverdhan et al., 2008).”

What the sources say

• Not checked yetcites Goverdhan et al., 2008 source

In the paper

“Their immunohistochemical analysis of AMD cases suggest that CX3CR1-positive microglial cells accumulated subretinally in affected areas of the macula”

What the sources say

• Not checked yetcites Combadiere et al., 2007 source

In the paper

“Taiwan Chinese carriers of the IL8 C781T variant, independent to the CFH Y402H variant, have also been shown to be at increased risk of developing wet AMD (Tsai et al., 2008).”

What the sources say

• Not checked yetcites Tsai et al., 2008 source

In the paper

“The AA genotype has also been shown to induce angiogenesis in rat cornea (Koch et al., 1992).”

What the sources say

• Not checked yetcites Koch et al., 1992 source

In the paper

“which suggested that CX3CR1-mediated decreases in inflammatory cell chemokinesis might contribute to age-related changes in the macula (Chan et al., 2005; Tuo et al., 2004)”

What the sources say

• Not checked yetcites Chan et al., 2005
• Not checked yetcites Tuo et al., 2004 source

In the paper

“Heterozygozity at the ARMS2/LOC387715 (A69A/A69S) is associated with odds ratio (OR) of 1.69–3.0 for advanced AMD, while homozygosity for the risk conferring allele (A69S/A69S) results in an OR of 2.20–12.1, after controlling for demographic and behavioral risk factors (Ross et al., 2007).”

What the sources say

• Not checked yetcites Ross et al., 2007 source

In the paper

“A genome-wide scan and genetic linkage analysis of 70 families with AMD suggests that chromosome 10q26 may contain a common AMD gene (Majewski et al., 2003).”

What the sources say

• Not checked yetcites Majewski et al., 2003 source

In the paper

“The risk-conferring ARMS2/LOC387715 SNP, A69S, is associated with AMD.”

In the paper

“Heterozygozity at the ARMS2/LOC387715 (A69A/A69S) is associated with odds ratio (OR) of 1.69–3.0 for advanced AMD, while homozygosity for the risk conferring allele (A69S/A69S) results in an OR of 2.20–12.1, after controlling for demographic and behavioral risk factors (Ross et al., 2007).”

What the sources say

• Not checked yetcites Ross et al., 2007 source

In the paper

“The association of ARMS2 gene with AMD, especially advanced AMD, susceptibility has now been replicated in numbers of independent studies (Conley et al., 2006; Rivera et al., 2005; Ross et al., 2007; Schmidt et al., 2006; Seddon et al., 2007; Kanda et al., 2007).”

What the sources say

• Not checked yetcites Conley et al., 2006 source
• Not checked yetcites Rivera et al., 2005 source
• Not checked yetcites Ross et al., 2007 source

In the paper

“Interestingly, an even stronger effects on AMD risk has been noted in patients with both the risk-conferring ARMS2 variant and elevated serum levels of several inflammatory markers including CRP, IL-6, soluble intercellular adhesion molecule 1 (sICAM-1) (Wang et al., 2008).”

What the sources say

• Not checked yetcites Wang et al., 2008 source

In the paper

“In the same study, individuals homozygous for the risk allele (genotype AA) expressed higher levels of HtrA1 in their circulating lymphocytes in vivo, compared with individuals homozygous for the non-risk variant (genotype GG).”

In the paper

“As a consequence, expression of ARMS2 in homozygous carriers of the deletion-insertion variant is absent, or at least sufficiently low to be experimentally undetectable.”

In the paper

“First, studies have shown that human donor AMD eyes contain higher levels of protein adducts resulting from the oxidative modification of carbohydrates and lipids (Crabb et al., 2002; Howes et al., 2004) and higher levels of antioxidant enzymes (Decanini et al., 2007; Frank et al., 1999) compared with non-AMD eyes, which indicate that oxidative stress plays an important role in AMD.”

In the paper

“As rs11200638 is located within a CpG island of the proximal promoter, 512 bp upstream of the HtrA1 transcription start site, the risk allele “A” of HtrA1 SNP was shown to enhance HtrA1 transcription in vitro in RPE cell lines (Dewan et al., 2006).”

What the sources say

• Not checked yetcites Dewan et al., 2006 source

In the paper

“Kanda et al. reported that ARMS2 is localized to the ellipsoid region of the photoreceptors in retina, where most of the mitochondria are located (Kanda et al., 2007).”

What the sources say

• Not checked yetcites Kanda et al., 2007 source

In the paper

“More recently, Fritsche et al. showed that a deletion-insertion polymorphism (*372_815delins54), which resides within the 3′-UTR of the ARMS2 gene, also associates very significantly with AMD (Fritsche et al., 2008).”

What the sources say

• Not checked yetcites Fritsche et al., 2008 source

In the paper

“We have also found the association between ApoE112R (E4) and a decreased risk of AMD development, and the underlying mechanisms might involve differential regulation of both CCL2 and VEGF by the ApoE isoforms (Bojanowski et al., 2006).”

What the sources say

• Not checked yetcites Bojanowski et al., 2006 source

In the paper

“Elevated expression of HtrA1 mRNA and/or protein in the drusen and CNV components in AMD patients carrying the AA risk genotype has been reported in several studies (Cameron et al., 2007; Chan et al., 2007; Tuo et al., 2008; Yang et al., 2006) (Fig. 6).”

What the sources say

• Not checked yetcites Cameron et al., 2007 source
• Not checked yetcites Chan et al., 2007
• Not checked yetcites Tuo et al., 2008 source

In the paper

“These findings suggest a possible role for ApoE in AMD pathology via retinal lipid trafficking (Ishida et al., 2004).”

What the sources say

• Not checked yetcites Ishida et al., 2004 source

In the paper

“In AMD patients, the presence of ApoE has been illustrated in drusen (Shanmugaratnam et al., 1997).”

What the sources say

• Not checked yetcites Shanmugaratnam et al., 1997 source

In the paper

“VEGF plays a critical role in the pathogenesis of neovascular AMD, and recently, therapies targeting VEGF have shown promising results of significant improvement of central vision and reduction of CNV (Wylegala and Teper, 2007).”

What the sources say

• Not checked yetcites Wylegala and Teper, 2007

In the paper

“Although the exact biological roles of both the ARMS2 and HtrA1 genes in humans are unclear, SNP analyses have confirmed their association with AMD.”

In the paper

“However, a large, population-based, cross-sectional study (n = 10,139) using participants from the Atherosclerosis Risk in Communities Study found no association between AMD and any of the ApoE alleles in Australia (Kaur et al., 2006; Schmidt et al., 2005; Schultz et al., 2003; Wong et al., 2006).”

What the sources say

• Not checked yetcites Kaur et al., 2006 source
• Not checked yetcites Schmidt et al., 2005
• Not checked yetcites Schultz et al., 2003 source

In the paper

“There is ample evidence that inflammation plays an important role in both dry and wet AMD.”

In the paper

“These data suggest that DNA repair mechanisms may play a role in AMD pathogenesis.”

In the paper

“Several groups have demonstrated the presence of macrophages at neovascular membranes in wet AMD (Dastgheib and Green, 1994; Grossniklaus et al., 2002; Penfold et al., 2001).”

What the sources say

• Not checked yetcites Dastgheib and Green, 1994
• Not checked yetcites Grossniklaus et al., 2002
• Not checked yetcites Penfold et al., 2001 source

In the paper

“They identified variants in one allele of the gene in 16% of the AMD patients (Allikmets, 1997; Allikmets et al., 1997).”

What the sources say

• Not checked yetcites Allikmets, 1997
• Not checked yetcites Allikmets et al., 1997

In the paper

“Moreover, multiple subsequent studies showed little or no relation of ABCA4 mutations with AMD (Bojanowski et al., 2005; De La Paz et al., 1999; Souied et al., 2000; Stone et al., 1998).”

What the sources say

• Not checked yetcites Bojanowski et al., 2005
• Not checked yetcites De La Paz et al., 1999 source
• Not checked yetcites Souied et al., 2000

In the paper

“Moreover, macrophages in CNV lesions have been shown to express proangiogenic factors such as VEGF and tissue factor (Csaky et al., 2004; Grossniklaus et al., 2002).”

What the sources say

• Not checked yetcites Csaky et al., 2004 source
• Not checked yetcites Grossniklaus et al., 2002

In the paper

“While AMD is not a classic inflammatory disease like uveitis; inflammatory cells, in particular the macrophages, have been histologically demonstrated near AMD lesions, including in areas of Bruch membrane breakdown, RPE atrophy, and choroidal neovascularization (Coleman et al., 2008; Dastgheib and Green, 1994; Green, 1999; Grossniklaus et al., 2002; Lopez et al., 1993; Penfold et al., 2001).”

What the sources say

• Not checked yetcites Coleman et al., 2008
• Not checked yetcites Dastgheib and Green, 1994
• Not checked yetcites Green, 1999

In the paper

“A disease OR of 23 was conferred by homozygosity for risk alleles at both ERCC6 and CFH compared with homozygosity for non-risk alleles.”

In the paper

“However, Richardson et al. (2007) provided a thorough tag-SNP based examination and found little evidence to support an association of the VEGF-A gene with AMD.”

What the sources say

• Not checked yetcites Richardson et al., 2007

In the paper

“As described above, the CX3CR1 chemokine receptor found on microglia has been shown to harbor SNPs (T280M and V249I) that have been associated with increased risk of AMD in some reports (Chan et al., 2005; Tuo et al., 2004).”

What the sources say

• Not checked yetcites Chan et al., 2005
• Not checked yetcites Tuo et al., 2004 source

In the paper

“Since microglia are already present in the retina since embryological development and do not chemotactically enter the retina, these SNPs might lead to impaired microglial migration or egress from the retina, resulting in accumulation of microglia.”

In the paper

“Eventually, by 16–18 months of age, Ccl2−/− and Ccr2−/− mice also develop geographic RPE atrophy and choroidal neovascularization.”

In the paper

“The notion that microglia contribute to drusen-like deposits is further strengthened by another study demonstrating that increasing fundus autofluorescence seen in aging wild-type mice consists of perivascular and subretinal microglia, which might also contain lipofuscin granules (Xu et al., 2008).”

What the sources say

• Not checked yetcites Xu et al., 2008

In the paper

“While the presence of macrophages at CNV lesions is largely recognized, the role of these macrophages presents some controversy as to whether these macrophages serve an adaptive role to combat CNV or a causative role in inducing CNV.”

In the paper

“In short, the Ccl2−/− and Ccr2−/− murine models of AMD suggest a protective role for macrophages in AMD pathogenesis—clearance of deposits.”

In the paper

“The CX3CR1 SNP is associated with impaired microglial chemotaxis (Combadiere et al., 2007).”

What the sources say

• Not checked yetcites Combadiere et al., 2007 source

In the paper

“Indeed, histological analysis of AMD retinas has depicted the presence of many activated microglia in the macular lesions (Gupta et al., 2003).”

What the sources say

• Not checked yetcites Gupta et al., 2003 source