MD Research News – Issue 427 – 27 June 2019
Drug treatment
Ophthalmol Retina. 2019 Apr 26. pii: S2468-6530(18)30749-8.
Pain control after intravitreal injection using topical nepafenac 0.3% or pressure patching: a randomized, placebo-controlled trial.
Kaplan RI, Drinkwater OJ, Lee RH, Chod RB, Barash A, Giovinazzo JV, Gologorsky D, Jansen ME, Rosen RB, Gentile RC.
Purpose: Pain after an intravitreal injection (IVI) can last up to 7 days and negatively impacts the patient's experience, potentially reducing treatment compliance. We prospectively evaluated topical nepafenac 0.3% suspension and patching for the reduction of pain after IVI.
Design: Randomized controlled trial.
Participants: Sixty patients receiving an IVI of bevacizumab, aflibercept, or triamcinolone acetonide in 1 eye.
Methods: Participants were randomized equally to receive either a single drop of nepafenac 0.3%, a pressure patch for 2 hours, or a single drop of preservative-free artificial tears (control group). A single-blinded placebo-controlled design was used to mask the topical treatment used. Pain was assessed using the Numeric Pain Rating Scale that ranged from 0 to 10 (horizontal pain scale). Because pain scores were not normally distributed, statistical analysis was performed using a nonparametric randomization-based analysis of covariance.
Main Outcome Measure: Pain scores.
Results: Fifty-six and 53 patients of the 60 patients enrolled completed the 6- and 24-hour follow-ups, respectively. Numeric Pain Rating Scale scores at 6 and 24 hours after IVI were lower in the nepafenac group (0.8±0.3 and 0.1±0.1, respectively; n = 18) and the patching group (1.3±0.4 and 0.4±0.2, respectively; n = 19) compared with the control group (2.5±0.6 and 0.9±0.4, respectively; n = 19). After controlling for age, gender, number of prior injections, and physician administering the injection, patients in the nepafenac group reported significantly lower pain scores than those in the control group at 6 hours (1.3±0.6 less; P = 0.047) and 24 hours (0.7±0.3 less; P = 0.047). Although the patching group reported lower pain scores than the control group, this was not statistically significant (6 hours, P = 0.24; 24 hours, P = 0.29).
Conclusions: Nepafenac 0.3% was effective as a single drop in reducing pain at 6 and 24 hours after IVI compared with placebo. Limited patching was associated with lower pain scores than placebo, but the difference was not statistically significant. Additional studies are needed to determine the most effective method to maximize the patient's experience after an IVI without sacrificing outcomes.
PMID: 31221565 DOI: 10.1016/j.oret.2019.04.022
BMC Ophthalmol. 2019 Jun 17;19(1):129.
Retinal function determined by flicker ERGs before and soon after intravitreal injection of anti-VEGF agents.
Terauchi G, Shinoda K, Sakai H, Kawashima M, Matsumoto CS, Mizota A, Miyake Y.
Background: To evaluate the retinal function before and soon after an intravitreal injection of an anti-vascular endothelial growth factor (anti-VEGF) agents.
Methods: Seventy-nine eyes of 79 patients that were treated by an intravitreal injection of an anti-VEGF agent for age-related macular degeneration (AMD), diabetic macular edema (DME), or retinal vein occlusion (RVO) with macular edema (ME) were studied. The RETeval® system was used to record 28 Hz flicker electroretinograms (ERGs) from the injected and non-injected eyes before (Phase 1, P1), within 2 h after the injection (P2), and 2 to 24 h after the injection (P3). Patients were grouped by disease or by the injected agent and compared. The significance of the changes in the implicit times and amplitudes was determined by t tests.
Results: The amplitudes were not significantly different at the three phases. The implicit time of the injected eye was 31.2 ± 3.2 msec at P1, and it was not significantly different at P2 (31.7 ± 3.1 msec) but it was significantly longer at P3 (32.2 ± 3.3 msec, P < 0.01, ANOVA for both). The implicit time in the non-injected fellow eye was 30.5 ± 3.3 msec at P1, and it was significantly longer at P2 (31.1 ± 3.2 msec) and phase 3 (31.3 ± 3.4 msec, P < 0.01, ANOVA for both).
Conclusions: The results indicate that an intravitreal anti-VEGF injection will increase the implicit times not only in the injected eye but also in the non-injected eye soon after the intravitreal injection.
PMID: 31208350 DOI: 10.1186/s12886-019-1129-7
Am J Ophthalmol. 2019 Jun 12. pii: S0002-9394(19)30275-2.
Changes in management based on vitreous culture in endophthalmitis after intravitreal anti-vascular endothelial growth factor injection.
Patel SN, Storey PP, Pancholy M, Obeid A, Wibbelsman TD, Levin H, Hsu J, Garg SJ, Dunn JP, Vander JF.
Purpose: To assess whether vitreous culture results affect the clinical management of patients with acute endophthalmitis after intravitreal anti-vascular endothelial growth factor (VEGF) injection.
Design: Retrospective case series - single-center.
Study population: Patients who developed endophthalmitis after intravitreal injection of aflibercept, bevacizumab, or ranibizumab between 1/1/2016 and 5/31/2018.
Observation: A change in clinical management was defined as additional intravitreal antibiotic injections or pars plana vitrectomy.
Main Outcome Measures: A change in clinical management within 2 weeks of initial endophthalmitis culture and treatment; visual acuity.
Results: Of 204,986 intravitreal anti-VEGF injections performed, 60 cases (0.0293%) of endophthalmitis were identified, 18 of which were culture-positive. Six of 60 eyes (10%) had a change in clinical management. A change in clinical management was initiated in 3 of 18 (17%) culture-positive cases compared to 3 of 42 (7%) culture-negative cases (p=0.357). Changes in management for culture-positive cases were performed based on declining vision (2 cases) and worsening clinical exam (1 case). Changes in management for culture-negative endophthalmitis cases were performed based on declining vision (1 case) and worsening clinical exam (2 cases). No additional interventions were initiated based on positive-culture results. Comparing vision loss from baseline by culture result, at final follow up, oral flora-associated culture-positive cases lost 17.5 lines, non-oral flora-associated culture-positive cases lost 9.1 lines, and culture-negative cases lost 2.5 lines of vision (p<0.001).
Conclusion: Following endophthalmitis from intravitreal injection of anti-VEGF agents, vitreous culture data may help prognosticate visual outcomes but appear to have a limited effect on clinical management.
PMID: 31201794 DOI: 10.1016/j.ajo.2019.06.008
Imaging and Artificial Intelligence (AI)
Clin Exp Ophthalmol. 2019 Jun 19.
Development and validation of a deep learning algorithm for the detection of neovascular age-related macular degeneration from color fundus photographs.
Keel S, Li Z, Scheetz J, Robman L, Phung J, Makeyeva G, Aung KZ, Liu C, Yan X, Meng W, Guymer R, Chang R, He M.
Importance: Detection of early onset neovascular age-related macular degeneration (AMD) is critical to protecting vision.
Background: To describe the development and validation of a deep learning algorithm (DLA) for the detection of neovascular age-related macular degeneration.
Design: Development and validation of a DLA using retrospective datasets.
Participants: We developed and trained the DLA using 56,113 retinal images and an additional 86,162 images from an independent dataset to externally validate the DLA. All images were non-stereoscopic and retrospectively collected.
Methods: The internal validation dataset was derived from real-world clinical settings in China. Gold standard grading was assigned when consensus was reached by 3 individual ophthalmologists. The DLA classified 31,247 images as gradable and 24,866 as ungradable (poor quality or poor field definition). These ungradable images were used to create a classification model for image quality. Efficiency and diagnostic accuracy were tested using 86,162 images derived from the Melbourne Collaborative Cohort Study. Neovascular AMD and/or ungradable outcome in one or both eyes was considered referable.
Main Outcome Measures: Area under the receiver operating characteristic curve (AUC), sensitivity and specificity.
Results: In the internal validation dataset, the AUC, sensitivity and specificity of the DLA for neovascular AMD was 0.995, 96.7%, 96.4%, respectively. Testing against the independent external dataset achieved an AUC, sensitivity and specificity of 0.967, 100% and 93.4%, respectively. More than 60% of false positive cases displayed other macular pathologies. Among the false negative cases (internal validation dataset only), over half (57.2%) proved to be undetected detachment of the neurosensory retina or RPE layer.
Conclusions: This DLA shows robust performance for the detection of neovascular AMD amongst retinal images from a multi-ethnic sample and under different imaging protocols. Further research is warranted to investigate where this technology could be best utilized within screening and research settings. This article is protected by copyright. All rights reserved.
PMID: 31215760 DOI: 10.1111/ceo.13575
Pathogenesis
PLoS One. 2019 Jun 20;14(6):e0218457.
Metabolomics in serum of patients with non-advanced age-related macular degeneration reveals aberrations in the glutamine pathway.
Kersten E, Dammeier S, Ajana S, Groenewoud JMM, Codrea M, Klose F, Lechanteur YT, Fauser S, Ueffing M, Delcourt C, Hoyng CB, de Jong EK, den Hollander AI; EYE-RISK Consortium.
Abstract: Age-related macular degeneration (AMD) is a common, progressive multifactorial vision-threatening disease and many genetic and environmental risk factors have been identified. The risk of AMD is influenced by lifestyle and diet, which may be reflected by an altered metabolic profile. Therefore, measurements of metabolites could identify biomarkers for AMD, and could aid in identifying high-risk individuals. Hypothesis-free technologies such as metabolomics have a great potential to uncover biomarkers or pathways that contribute to disease pathophysiology. To date, only a limited number of metabolomic studies have been performed in AMD. Here, we aim to contribute to the discovery of novel biomarkers and metabolic pathways for AMD using a targeted metabolomics approach of 188 metabolites. This study focuses on non-advanced AMD, since there is a need for biomarkers for the early stages of disease before severe visual loss has occurred. Targeted metabolomics was performed in 72 patients with early or intermediate AMD and 72 control individuals, and metabolites predictive for AMD were identified by a sparse partial least squares discriminant analysis. In our cohort, we identified four metabolite variables that were most predictive for early and intermediate stages of AMD. Increased glutamine and phosphatidylcholine diacyl C28:1 levels were detected in non-advanced AMD cases compared to controls, while the rate of glutaminolysis and the glutamine to glutamate ratio were reduced in non-advanced AMD. The association of glutamine with non-advanced AMD corroborates a recent report demonstrating an elevated glutamine level in early AMD using a different metabolomics technique. In conclusion, this study indicates that metabolomics is a suitable method for the discovery of biomarker candidates for AMD. In the future, larger metabolomics studies could add to the discovery of novel biomarkers in yet unknown AMD pathways and expand our insights in AMD pathophysiology.
PMID: 31220133 DOI: 10.1371/journal.pone.0218457
Eur J Ophthalmol. 2019 Jun 17:1120672119857896.
Systemic activation of the complement system in patients with advanced age-related macular degeneration.
Lynch AM, Mandava N, Patnaik JL, Frazer-Abel AA, Wagner BD, Palestine AG, Mathias MT, Siringo FS, Cathcart JN, Holers VM.
Purpose: To examine the role of systemic activation of the complement system (assessed by levels of circulating C3a, Ba, and sC5b-9) in patients (n = 122) with advanced age-related macular degeneration, geographic atrophy, and neovascular age-related macular degeneration, compared with cataract controls (n = 27).
Methods: Plasma complement factors were measured using enzyme-linked immunosorbent assays. Statistical analysis included univariate and multivariate logistic regression (p < 0.05).
Results: Adjusted for age, the odds ratios of C3a and sC5b-9 for any advanced age-related macular degeneration were 1.78 (95% confidence interval = 1.16-2.73, p < 0.01) and 1.20 (95% confidence interval = 1.04-1.39, p = 0.01), respectively. We found a significantly elevated adjusted odds ratio of C3a (adjusted odds ratio = 1.71, 95% confidence interval = 1.12-2.60, p = 0.01) and sC5b-9 (adjusted odds ratio = 1.22, 95% confidence interval = 1.04-1.43, p = 0.01) for neovascular age-related macular degeneration. Adjusted for age, neither C3a, sC5b-9, nor Ba were associated with geographic atrophy.
Conclusion: We suggest a role for elevated plasma levels of C3a and sC5b-9 in patients with neovascular age-related macular degeneration. The study's results reinforce the need for more investigation to assess the impact of therapeutic interventions targeted at the complement signaling pathways in age-related macular degeneration.
PMID: 31203676 DOI: 10.1177/1120672119857896
Exp Eye Res. 2019 Jun 18:107701.
Age-related macular degeneration (AMD) mitochondria modulate epigenetic mechanisms in retinal pigment epithelial cells.
Nashine S, Nesburn AB, Kuppermann BD, Kenney MC.
Abstract: Mitochondrial damage and epigenetic modifications have been implicated in the pathogenesis of Age-related Macular Degeneration (AMD). Understanding the epigenetic mechanisms driven by AMD mitochondria may help in identifying molecular targets for therapeutic intervention in AMD. We herein characterized the interplay of AMD/normal mitochondria and epigenetic regulation in human transmitochondrial retinal pigment epithelial cybrid cells (RPE) in vitro. These human RPE cybrid cell lines were created by fusing mitochondria-deficient (Rho0) ARPE-19 cells with platelets obtained from either AMD patients (AMD cybrids) or normal subjects (normal cybrids). Therefore, all cybrids had identical nuclei (derived from ARPE-19 cells) but different mitochondria derived either from AMD patients or normal subjects. Our results revealed that AMD mitochondria regulate epigenetic mechanisms i.e., methylation and acetylation status. Demethylation using 5-Aza-2'-deoxycytidine (DAC) caused differential expression of VEGF-A gene in AMD cells. Trichostatin A (TSA), an HDAC inhibitor, also influenced protein levels of VEGF-A, HIF1α, NFκB, and CFH in AMD cells. This study might advance the field of AMD research since in addition to highlighting the critical role of nuclear-mitochondrial interactions that influence epigenetic mechanisms in AMD patients, this work suggests epigenetic profiles as potential therapeutic targets for AMD.
PMID: 31226340 DOI: 10.1016/j.exer.2019.107701
Low vision
J Vis. 2019 Jun 3;19(6):18.
Caricaturing can improve facial expression recognition in low-resolution images and age-related macular degeneration.
Lane J, Robbins RA, Rohan EMF, Crookes K, Essex RW, Maddess T, Sabeti F, Mazlin JL, Irons J, Gradden T, Dawel A, Barnes N, He X, Smithson M, McKone E.
Abstract: Previous studies of age-related macular degeneration (AMD) report impaired facial expression recognition even with enlarged face images. Here, we test potential benefits of caricaturing (exaggerating how the expression's shape differs from neutral) as an image enhancement procedure targeted at mid- to high-level cortical vision. Experiment 1 provides proof-of-concept using normal vision observers shown blurred images as a partial simulation of AMD. Caricaturing significantly improved expression recognition (happy, sad, anger, disgust, fear, surprise) by ∼4%-5% across young adults and older adults (mean age 73 years); two different severities of blur; high, medium, and low intensity of the original expression; and all intermediate accuracy levels (impaired but still above chance). Experiment 2 tested AMD patients, running 19 eyes monocularly (from 12 patients, 67-94 years) covering a wide range of vision loss (acuities 6/7.5 to poorer than 6/360). With faces pre-enlarged, recognition approached ceiling and was only slightly worse than matched controls for high- and medium-intensity expressions. For low-intensity expressions, recognition of veridical expressions remained impaired and was significantly improved with caricaturing across all levels of vision loss by 5.8%. Overall, caricaturing benefits emerged when improvement was most needed, that is, when initial recognition of uncaricatured expressions was impaired.
PMID: 31215978 DOI: 10.1167/19.6.18
Nutrients & antioxidants
Curr Dev Nutr. 2019 Jun 13;3(Suppl 1). pii: nzz029.P02-004-19.
Associations between serum lutein and human gut microbiota.
Dinsmoor A, Thompson S, Edwards C, Burd N, Khan N, Erdman J Jr, Holscher H.
Objectives: Lutein is a carotenoid found in green leafy vegetables, avocados, and eggs, and is purported to have protective effects against age-related macular degeneration (AMD) as well as benefits for visual and cognitive health. Recent studies have indicated significant variation in serum lutein among individuals and that gastrointestinal (GI) microbial profile may potentially contribute to lutein status. However, the extent to which the GI microbiota contribute to lutein is unclear. The current study aimed to determine GI microbial predictors of serum lutein in a healthy young adult population.
Methods: Among adults ages 25-45 years (N = 105), venous blood was collected following a 10-hour fast. Serum lutein was determined using HPLC. Fecal DNA was extracted and the V4 region of the 16S rRNA gene was amplified. Amplicon sequence variants were assigned using the GreenGenes 13-8 database and DADA2, followed by analysis in QIIME2 and LDA Effect Size (LEfSe). Participants underwent DXA scan for whole body % fat (%Fat) and completed a 7-day food record to assess lutein consumption. Demographic information on participant's age and sex was also assessed and included in the statistical models.
Results: Four genera (Dialister, Ruminococcus, Gemmiger, and Phascolarctobacterium) and two species (Bacteroides eggerthii, Ruminococcus torques) were different between individuals in the highest and lowest quartiles of serum lutein. The genera Ruminococcus (Rho = -0.24, P = 0.02) and Phascolarctobacterium (Rho = -0.21, P = 0.03) and species R. torques (Rho = -0.35, P < 0.001) were inversely related to serum lutein. Linear regression modelling, adjusted for age, sex, %Fat, and dietary lutein, revealed that R. torques was the only significant predictor of serum lutein concentrations, accounting for 8.4% of the variance.
Conclusions: Our results reveal that individuals with lower serum lutein concentrations have a higher relative abundance of R. torques than those with higher lutein concentrations. As R. torques has been shown to be elevated in those with AMD, it is possible the relationship between this microbe and lutein is evident earlier in adulthood. However, further dietary intervention trials are warranted to clarify the relations among R. torques and serum lutein concentrations.
PMID: 31224848 PMCID: PMC6575035 DOI: 10.1093/cdn/nzz029.P02-004-19
Curr Dev Nutr. 2019 Jun 13;3(Suppl 1). pii: nzz029.P02-006-19.
The content of lutein and zeaxanthin in the diet of young health people.
Korolev A, Kirpichenkova E, Nikitenko E, Denisova E.
Objectives: Lutein and zeaxanthin are non-vitamin carotenoids, which located in macula. These carotenoids reduce the risk of progression of age-related macular degeneration. The purpose of research to analyze the amount of lutein and zeaxanthin in diets of young health people and to assess food choices rich non-vitamin carotenoids.
Methods: Adults aged 20-25 y (n = 424, 113 males age 22.0 ± 0.9 y, 311 females age 22.0 ± 0.8 y). Lutein and zeaxanthin levels from food sources have been estimated using the 24-hour recall method. The questionnaire was designed specifically to conduct a specific study. It provided for the selection of food sources, and indication of the consumed amount of lutein and zeaxanthin.
Results: Of the 424 students only 24 (5.7%) have reached the recommended level (8.84 ± 3.39 mg/day). The main sources of lutein and zeaxanthin in this group were zucchini (29.2%); broccoli, lettuce, persimmon and spinach (12.5% each), pumpkin and parsley (8.3% each), peas (4.2%). The dietary intake of non-vitamin carotenoids for 41 students (9,7%) was 50.0-99.9% (4.19 ± 0.76 mg/day) of the recommended level. The student's diet of this group included sources of lutein and zeaxanthin such as lettuce (34.2%), broccoli (24.4%), zucchini (12.2%), corn and persimmon (7.3% each), pumpkin and spinach (4.9% each), orange juice and peas (2.4% each). Most of the study participants (306 students - 72.1%) had insufficient intake of lutein and zeaxanthin with food sources and was less than half of the recommended level (0.93 ± 0.82 mg/day). The major sources of non-vitamin carotenoids were eggs (22.9%); red raw tomatoes (15.0%); lettuce (11.1%); zucchini (7.2%); fast food products and orange juice (5.6% each); peas (4.9%); carrot (4.2%); ketchup (3.9%); parsley (3.6%); corn and persimmon (3.3% each); broccoli (2.3%); kiwi (1.6%); pumpkin (1.3%); basil, green onion, canned fish, celery, canned red tomatoes, tomato juice, pistachios and spinach (0.3-0.9%). Sources of lutein and zeaxanthin, such as Brussels sprouts, blackberries, blueberries, were not included in the diet. Moreover, 53 (12,5%) students had no sources of lutein and zeaxanthin in their diet.
Conclusions: For the most of students, the recommended intake of lutein and zeaxanthin was not achieved. The major food sources were included in the diet in insufficient quantities.
PMID: 31224957 PMCID: PMC6576148 DOI: 10.1093/cdn/nzz029.P02-006-19
PLoS One. 2019 Jun 19;14(6):e0218433.
Association of vitreous vitamin C depletion with diabetic macular ischemia in proliferative diabetic retinopathy.
Park SW, Ghim W, Oh S, Kim Y, Park UC, Kang J, Yu HG.
Purpose: Vitreous vitamin C, as an anti-oxidant, is responsible for regulating oxygen tension and oxidative stress in the eye. Oxidative stress and retinal ischemia are implicated in the development of proliferative diabetic retinopathy (PDR). In this study, we aimed to determine whether vitreous level of vitamin C is compromised in patients with PDR and to investigate the association of diabetic macular ischemia and vitamin C.
Methods: This prospective study enrolled forty patients who underwent pars plana vitrectomy for the treatment of PDR (PDR group, n = 20) and idiopathic epiretinal membrane (control group, n = 20). Serum, aqueous humor, and the vitreous were collected for the analysis of vitamin C level by HPLC. Diabetic macular ischemia (DMI) in PDR group was evaluated with fluorescein angiography (FA).
Results: PDR patients (60.4 ± 2.1 y) were younger than non-diabetic control patients (67.4 ± 1.2 y). Serum, aqueous, and vitreous levels of vitamin C in PDR were 38.7%, 22.5%, and 11.1% of non-diabetic control group, respectively. All PDR patients had DMI (grade 1: 25%, grade 2: 30%, grade 3: 30%, grade 4: 15%). DMI grade was inversely correlated with the level of vitreous vitamin C (r = -0.546, P = 0.019), not with HbA1C, serum, or aqueous vitamin C level. In addition, the level of vitreous vitamin C (4.5 ± 2.6 μg/ml) in high DMI group (Gr 3 &4) was lower than that (31.0 ± 9.1 μg/ml) in low DMI group (Gr 1&2) (P = 0.015).
Conclusions: Vitreous level of vitamin C in PDR patients showed a tenfold decrease, which was associated with the degree of macular ischemia. This suggests that vitreous vitamin C depletion may cause macula ischemia in PDR patients.
PMID: 31216331 DOI: 10.1371/journal.pone.0218433
Acta Biochim Pol. 2019 Jun 18;66(2):147-158.
Can vitamin D protect against age-related macular degeneration or slow its progression?
Kaarniranta K, Pawlowska E, Szczepanska J, Jablkowska A, Błasiak J.
Abstract: Dietary vitamin D plays an important role in maintaining proper vision. Age-related macular degeneration (AMD) is a complex eye disease with unknown pathogenesis. Studies on dietary supplementation and AMD occurrence and progression have produced conflicting results. In its advanced stage, AMD may be associated with apoptosis, pyroptosis or necroptosis of retinal cells. Vitamin D has been reported to play a role in modulating each of these programmed death pathways. Vitamin D is a modulator of the immune system and it acts synergistically with two members of the regulators of complement activation family H and I, whose specific variants are the most important genetic factors for AMD pathogenesis. Angiogenesis is an essential component of the neovascular form of AMD, the most devastating type of the disease and vitamin D is reputed to possess antiangiogenic properties. Cellular DNA damage response is weakened in AMD patients and so it is another process that can be modulated by vitamin D. Finally, impaired autophagy is claimed to play a role in AMD and emerging evidence suggests that vitamin D can influence autophagy. Therefore, several pathways of vitamin D metabolism and AMD pathogenesis overlap, suggesting that vitamin D could modulate the course of AMD.
PMID: 31210463 DOI: 10.18388/abp.2018_2810
Antioxidants (Basel). 2019 Jun 14;8(6). pii: E177.
Suppression of AMD-like pathology by mitochondria-targeted antioxidant SkQ1 is associated with a decrease in the accumulation of amyloid β and in mTOR activity.
Muraleva NA, Kozhevnikova OS, Fursova AZ, Kolosova NG.
Abstract: Age-related macular degeneration (AMD) is a major cause of irreversible visual impairment and blindness in developed countries, and the molecular pathogenesis of AMD is poorly understood. Recent studies strongly indicate that amyloid β (Aβ) accumulation —found in the brain and a defining feature of Alzheimer's disease— also forms in the retina in both Alzheimer's disease and AMD. The reason why highly neurotoxic proteins of consistently aggregate in the aging retina, and to what extent they contribute to AMD, remains to be fully addressed. Nonetheless, the hypothesis that Aβ is a therapeutic target in AMD is debated. Here, we showed that long-term treatment with SkQ1 (250 nmol/[kg body weight] daily from the age of 1.5 to 22 months) suppressed the development of AMD-like pathology in senescence-accelerated OXYS rats by reducing the level of Aβ and suppressing the activity of mTOR in the retina. Inhibition of mTOR signaling activity, which plays key roles in aging and age-related diseases, can be considered a new mechanism of the prophylactic effect of SkQ1. It seems probable that dietary supplementation with mitochondria-targeted antioxidant SkQ1 can be a good prevention strategy to maintain eye health and possibly a treatment of AMD.
PMID: 31208023 DOI: 10.3390/antiox8060177