Important Causes of Visual Impairment in the World Today

Congdon, Nathan; Friedman, David S.; Lietman, Thomas M.

doi:10.1001/jama.290.15.2057

Cited by 645 publications

(425 citation statements)

References 36 publications

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“…Among these disorders, cataract is the leading cause of blindness worldwide and accounts for estimated cases of 18 million, half of all these cases originating in developing countries (6,7). Several large-scale population-based epidemiological studies consistently revealed strong links between obesity and cataract (5,(8)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Increased risk of cataract development in WNIN‐obese rats due to accumulation of intralenticular sorbitol

et al. 2013

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Epidemiological studies have reported an association between obesity and increased incidence of ocular complications including cataract, yet the underlying biochemical and molecular mechanisms remained unclear. Previously we had demonstrated accumulation of sorbitol in the lens of obese rats (WNIN/Ob) and more so in a related strain with impaired glucose tolerance (WNIN/GR-Ob). However, only a few (15-20%) WNIN/Ob and WNIN/GR-Ob rats develop cataracts spontaneously with age. To gain further insights, we investigated the susceptibility of eye lens proteins of these obese rat strains to heat-and UV-induced aggregation in vitro, lens opacification upon glucose-mediated sorbitol accumulation ex vivo, and onset and progression of cataract was followed by galactose feeding and streptozotocin (STZ) injection. The results indicated increased susceptibility toward heat-or UV-induced aggregation of lens proteins in obese animals compared to their littermate lean controls. Further, in organ culture studies glucose-induced sorbitol accumulation was found to be higher and thus the lens opacification was faster in obese animals compared to their lean littermates. Also, the onset and progression of galactose-or STZ-induced cataractogenesis was faster in obese animals compared to lean control. These results together with our previous observations suggest that obesity status could lead to hyperaccumulation of sorbitol in eye lens, predisposing them to cataract, primarily by increasing their susceptibility to environmental and/or physiological factors. Further, intralenticular sorbitol accumulation beyond a threshold level could lead to cataract in WNIN/Ob and WNIN/ GR-Ob rats. V C 2013 IUBMB Life, 65(5): [472][473][474][475][476][477][478] 2013

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Section: Introductionmentioning

confidence: 99%

Increased risk of cataract development in WNIN‐obese rats due to accumulation of intralenticular sorbitol

et al. 2013

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“…Age-related macular degeneration (AMD) is the most common cause of blindness in people over 50 years of age in the developed world (Bressler, 2004;Congdon et al, 2003;Klein et al, 1995). This degenerative disease results in a loss of central and colour vision, leading to difficulty with reading, recognizing faces, and driving, thus impacting profoundly on the independence of those affected.…”

Section: Introductionmentioning

confidence: 99%

The association between macular pigment optical density and CFH, ARMS2, C2/BF, and C3 genotype

Loane

Nolan

McKay

et al. 2011

Experimental Eye Research

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Keywords: age-related macular degeneration age-related maculopathy susceptibility 2 gene carotenoids Complement factor H lutein macular pigment zeaxanthin a b s t r a c t Age-related macular degeneration (AMD) is the most common cause of blindness in older people in developed countries, and risk for this condition may be classified as genetic or environmental, with an interaction between such factors predisposing to this disease. This study investigated the relationship between AMD risk genes, macular pigment optical density (MPOD), which may protect against AMD, and serum concentrations of the macular carotenoids, lutein (L) and zeaxanthin (Z). This was a cross-sectional study of 302 healthy adult subjects. Dietary intake of L and Z was assessed by food frequency questionnaire, and MPOD was measured by customized heterochromatic flicker photometry. We also calculated MPOD Area as the area of MP under the spatial profile curve, to reflect MP across the macula. Serum L and Z were measured by HPLC. Genotyping of tag SNPs in the genes CFH, ARMS2, C3, C2 and BF was undertaken with multiplex polymerase chain reaction (PCR) and primer extension methodology (ABI Snapshot, ABI Warrington UK) on DNA extracted from peripheral blood. The mean AE SD (range) age of the subjects in this study was 48 AE 11 (21e66) years. There was a statistically significant association between CFH genotype and family history of AMD, with subjects having two non-risk CFH haplotypes (n ¼ 35), or one non-risk and one protective CFH haplotype (n ¼ 33), being significantly more likely to have a negative family history of AMD (Pearson Chi square: p ¼ 0.001). There was no significant association between the AMD risk genes investigated and either MPOD (One way ANOVA: p > 0.05) or serum concentrations of L or Z (One way ANOVA: p > 0.05, for both). Subjects who were homozygous for risk alleles of both CFH and ARMS2 (n ¼ 4) had significantly lower MPOD at 0.5 and 1 retinal eccentricity (Independent samples t test: p < 0.05) and lower MPOD Area which approached statistical significance (Independent samples t test: p ¼ 0.058), compared to other subjects (n ¼ 291). In conclusion, this study did not detect an association between individual AMD risk genotypes and the putatively protective MP, or serum concentrations of its constituent carotenoids. However, the combination of homozygous risk alleles at both CFH and ARMS2 loci was associated with significantly lower MPOD centrally, despite comparable serum concentrations of the macular carotenoids. These findings suggest that the maculae of subjects at very high genetic risk of AMD represent a hostile environment for accumulation and/or stabilization of MP.

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“…Proliferative diabetic retinopathy (PDR) is a leading cause of blindness and visual impairment among adults aged <40 years in the developed world [1]. Investigations into the processes involved in PDR and the testing of new therapies are limited because of the unavailability of human retina samples and the lack of diabetic animal models that faithfully replicate the features of human PDR.…”

Section: Introductionmentioning

confidence: 99%

Proteomic analysis of human vitreous fluid by fluorescence-based difference gel electrophoresis (DIGE): a new strategy for identifying potential candidates in the pathogenesis of proliferative diabetic retinopathy

Garcia-Ramírez

Canals

Hernández³

et al. 2007

Diabetologia

151

135

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Aims/hypothesis The aim of this study was to compare the protein profile of vitreous fluid from diabetic patients with proliferative diabetic retinopathy (PDR) with that from nondiabetic patients with idiopathic macular holes (MH). The mRNA of proteins differentially produced was also assessed in the retinas from diabetic and non-diabetic donors. Materials and methods Vitreous humour from type 1 diabetic patients with PDR (n=8) and from non-diabetic patients with MH (n=10) closely matched in terms of age were studied. The comparative proteomic analysis was performed using fluorescence-based difference gel electrophoresis (DIGE). Differentially produced proteins (abundance ratio >1.4, p<0.05) were identified by mass spectrometry. Expressions of mRNA were measured by real-time RT-PCR in retinas from ten human eyes obtained at post-mortem (five eyes from diabetic subjects and five eyes from non-diabetic subjects). Results Eight proteins were highly produced in PDR patients in comparison with non-diabetic subjects: zinc-α 2 -glycoprotein (ZAG), apolipoprotein (apo) A1, apoH, fibrinogen A, and the complement factors C3, C4b, C9 and factor B). We found three proteins that were underproduced in PDR subjects: pigment epithelial derived factor (PEDF), interstitial retinol-binding protein (IRBP) and inter-α-trypsin inhibitor heavy chain (ITIH2). There was no overlap in the vitreous levels of the above-mentioned proteins between PDR patients and non-diabetic control subjects. The differential production of ZAG, C3, factor B, PEDF and IRBP was further confirmed by western blot, and was in agreement with mRNA levels detected in the retina. Conclusions/interpretation Proteomic analysis by DIGE, which permits an accurate quantitative comparison, was useful in identifying new potential candidates involved in the pathogenesis of PDR.

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Important Causes of Visual Impairment in the World Today

Cited by 645 publications

References 36 publications

Increased risk of cataract development in WNIN‐obese rats due to accumulation of intralenticular sorbitol

Increased risk of cataract development in WNIN‐obese rats due to accumulation of intralenticular sorbitol

The association between macular pigment optical density and CFH, ARMS2, C2/BF, and C3 genotype

Proteomic analysis of human vitreous fluid by fluorescence-based difference gel electrophoresis (DIGE): a new strategy for identifying potential candidates in the pathogenesis of proliferative diabetic retinopathy

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