Hemoglobin-Induced Lipid Peroxidation in the Retina: A Possible Mechanism for Macular Degeneration

Ito, Takashi; Nakano, Mariko; Yamamoto, Yorihiro; Hiramitsu, Tadahisa; Mizuno, Yota

doi:10.1006/abbi.1995.1116

Cited by 38 publications

(25 citation statements)

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“…7,8,56 Markers of lipid oxidation including plasma levels of malondialdehyde (MDA), 54,55 and thiobarbituric acid-reactive substance (TBARS), have been shown to be higher in serum of patients with AMD compared with controls without AMD in previous studies. 52,53 However, F2-IsoPs have been shown to have greater utility than these markers. First, urinary F2-IsoPs are very stable because artifactual F 2 -IsoPs are not formed by auto-oxidation due to the low lipid content of urine 38 as opposed to MDA and TBARS.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies have provided evidence supporting the role of lipid peroxidation in AMD. [52][53][54][55] The RPE has been shown to be highly vulnerable to oxidative stress by radicalcatalyzed lipid peroxidation. 7,8,56 Markers of lipid oxidation including plasma levels of malondialdehyde (MDA), 54,55 and thiobarbituric acid-reactive substance (TBARS), have been shown to be higher in serum of patients with AMD compared with controls without AMD in previous studies.…”

Section: Discussionmentioning

confidence: 99%

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Urinary Isoprostane Levels and Age-Related Macular Degeneration

Sabanayagam

Lye

Januszewski

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Oxidative stress, characterized by an excessive production of reactive oxygen intermediates has been suggested to play a role in the pathogenesis of age-related macular degeneration (AMD). We examined the association of urinary F2-isoprostanes (F2-IsoPs), a marker of lipid peroxidation and the most reliable marker of oxidative damage with AMD. METHODS.We included 238 adults with AMD and 390 age-and sex-matched controls without AMD who participated in a population-based cross-sectional study in Singapore (Singapore Chinese Eye Study, 2009-2011. AMD was graded from retinal photographs using the Wisconsin Age-Related Maculopathy Grading System. Urinary-free F2-IsoPs (pmol/mmol of creatinine) were measured by gas chromatography mass spectrometry (GC-MS). The association between F2-IsoPs and AMD was examined using unconditional logistic regression models adjusted for potential confounders including smoking, body mass index (BMI), blood pressure, total and high-density lipoprotein cholesterol, and history of cardiovascular disease. RESULTS.Higher levels of F2-IsoPs were associated with AMD independent of potential confounders. Compared to quartile 1 (Q1) of F2-IsoPs, the multivariable odds ratio (95% confidence interval) of AMD in quartiles 2, 3, and 4 were 2.05 (1.26-3.32), 1.80 (1.10-2.94), and 1.76 (1.06-2.94), respectively. In subgroup analyses comparing Q4 to Q1, this association was stronger in women, those with BMI less than 25 kg/m 2 and those with hypertension, but no significant interaction was found (P interaction > 0.1 for each strata).CONCLUSIONS. Higher levels of urinary F2-IsoPs levels were associated with AMD independent of potential confounders in Chinese adults.Keywords: age-related macular degeneration, Asians, isoprostane, oxidative stress A ge-related macular degeneration (AMD) is a leading cause of irreversible blindness in older adults worldwide.1,2 Globally, 170 million adults have AMD, exerting a significant socioeconomic burden on healthcare systems.2,3 Despite significant research over decades, the pathogenesis of AMD is still not clear, and robust systemic biomarkers of AMD have not been identified yet. 4 Oxidative stress, characterized by an imbalance between excessive generation of reactive oxygen species (ROS) and their degradation by antioxidants, has recently been proposed to play a significant role in the pathogenesis of AMD. [5][6][7] With advancing age, the retina becomes more susceptible to oxidative stress and damage to the retinal pigment epithelium (RPE) occurs early in the natural history of AMD.8 At physiological concentrations, ROS are involved in cell signaling and regulation of immune responses. 9 However, disproportionate levels of ROS with concurrent impairment of enzymatic and nonenzymatic antioxidants damage cellular proteins, membrane lipids, and DNA that eventually lead to tissue injury, cellular death 10 resulting in accumulation of detrimental products including intracellular lipofuscin, and extracellular drusen. 6Oxidation of membrane lipids or lipid pero...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Urinary Isoprostane Levels and Age-Related Macular Degeneration

Sabanayagam

Lye

Januszewski

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…This proposed role is intriguing, because retinal cell edema is associated with pathologies such as ischemia and reperfusion during diabetic retinopathy, macular edema, and neurodegeneration (15,24). Taurine has been proposed also to function as an antioxidant.…”

Section: Author Manuscript Author Manuscriptmentioning

confidence: 99%

Regulation of taurine transporter expression by NO in cultured human retinal pigment epithelial cells

Bridges¹,

Ola²,

Prasad³

et al. 2001

American Journal of Physiology-Cell Physiology

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Taurine is actively transported at the retinal pigment epithelial (RPE) apical membrane in an Na(+)- and Cl(-)-dependent manner. Diabetes may alter the function of the taurine transporter. Because nitric oxide (NO) is a molecule implicated in the pathogenesis of diabetes, we asked whether NO would alter the activity of the taurine transporter in cultured ARPE-19 cells. The activity of the transporter was stimulated in the presence of the NO donor 3-morpholinosydnonimine. The stimulatory effects of 3-morpholinosydnonimine were not observed during the initial 16-h treatment; however, stimulation of taurine uptake was elevated dramatically above control values with 20- and 24-h treatments. Kinetic analysis revealed that the stimulation was associated with an increase in the maximal velocity of the transporter with no significant change in the substrate affinity. The NO-induced increase in taurine uptake was inhibited by actinomycin D and cycloheximide. RT-PCR analysis and nuclear run-on assays provided evidence for upregulation of the transporter gene. This study provides the first evidence of an increase in taurine transporter gene expression in human RPE cells cultured under conditions of elevated levels of NO.

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“…A possible explanation could be the shearing of the photoreceptor outer segments from contracting fibrin in the blood [33] and the scarring and atrophy given by subretinal bleeding, secondary to an oxidative damage of the devitalized blood [34]. Subretinal blood accumulates in the extracellular space between the RPE and the photoreceptor outer segments, so toxic compounds coming from the blood through iron-catalyzed free radicals attack lipids through the Fenton reaction [35]. Free radicals and peroxidized lipids induce scarring and atrophy to the retina and RPE.…”

Section: Discussionmentioning

confidence: 99%

Intravitreal Ranibizumab for Predominantly Hemorrhagic Choroidal Neovascularization in Age-Related Macular Degeneration

et al. 2015

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Purpose: To evaluate the effects of intravitreal ranibizumab monotherapy on predominantly hemorrhagic choroidal neovascularization with foveal involvement associated with age-related macular degeneration. Materials and Methods: Twenty-two consecutive eyes with hemorrhagic neovascularization were treated with 3 monthly intravitreal ranibizumab injections. Additional injections were administered according to retreatment criteria during 12 months of follow-up. Results: A mean of 6.64 ± 1.36 injections was administered. Overall, the mean visual acuity increased from 10.90 ± 6.02 to 12.81 ± 8.34 ETDRS letters (p > 0.05) at 12 months. The ‘early treatment group' gained a mean of 2.83 ± 2.24 ETDRS letters (p < 0.05), while the ‘late treatment group' gained a mean of 0.30 ± 1.25 ETDRS letters (p > 0.05) with significant differences between the groups (p < 0.05). A progressive resolution of macular bleeding was registered in 20 patients (mean time: 5.3 ± 1.6 months). Conclusions: Ranibizumab injections can be considered a beneficial approach for the management of predominantly hemorrhagic choroidal neovascularization with foveal involvement associated with age-related macular degeneration. Furthermore, the time interval between hemorrhage and the first injection seems to be an important predicting factor of final visual acuity.

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Hemoglobin-Induced Lipid Peroxidation in the Retina: A Possible Mechanism for Macular Degeneration

Cited by 38 publications

References 0 publications

Urinary Isoprostane Levels and Age-Related Macular Degeneration

Urinary Isoprostane Levels and Age-Related Macular Degeneration

Regulation of taurine transporter expression by NO in cultured human retinal pigment epithelial cells

Intravitreal Ranibizumab for Predominantly Hemorrhagic Choroidal Neovascularization in Age-Related Macular Degeneration

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