Single-cell transcriptomics reveals maturation of transplanted stem cell-derived retinal pigment epithelial cells toward native state.

Transplantation of stem cell-derived retinal pigment epithelial (RPE) cells is considered a viable therapeutic option for age-related macular degeneration (AMD). Several landmark Phase I/II clinical trials have demonstrated safety and tolerability of RPE transplants in AMD patients, albeit with limited efficacy. Currently, there is limited understanding of how the recipient retina regulates the survival, maturation, and fate specification of transplanted RPE cells. To address this, we transplanted stem cell-derived RPE into the subretinal space of immunocompetent rabbits for 1 mo and conducted single-cell RNA sequencing analyses on the explanted RPE monolayers, compared to their age-matched in vitro counterparts. We observed an unequivocal retention of RPE identity, and a trajectory-inferred survival of all in vitro RPE populations after transplantation. Furthermore, there was a unidirectional maturation toward the native adult human RPE state in all transplanted RPE, regardless of stem cell resource. Gene regulatory network analysis suggests that tripartite transcription factors (FOS, JUND, and MAFF) may be specifically activated in posttransplanted RPE cells, to regulate canonical RPE signature gene expression crucial for supporting host photoreceptor function, and to regulate prosurvival genes required for transplanted RPE's adaptation to the host subretinal microenvironment. These findings shed insights into the transcriptional landscape of RPE cells after subretinal transplantation, with important implications for cell-based therapy for AMD.

Stretchable ionic-electronic bilayer hydrogel electronics enable in situ detection of solid-state epidermal biomarkers.

Continuous and in situ detection of biomarkers in biofluids (for example, sweat) can provide critical health data but is limited by biofluid accessibility. Here we report a sensor design that enables in situ detection of solid-state biomarkers ubiquitously present on human skin. We deploy an ionic-electronic bilayer hydrogel to facilitate the sequential dissolution, diffusion and electrochemical reaction of solid-state analytes. We demonstrate continuous monitoring of water-soluble analytes (for example, solid lactate) and water-insoluble analytes (for example, solid cholesterol) with ultralow detection limits of 0.51 and 0.26 nmol cm-2, respectively. Additionally, the bilayer hydrogel electrochemical interface reduces motion artefacts by a factor of three compared with conventional liquid-sensing electrochemical interfaces. In a clinical study, solid-state epidermal biomarkers measured by our stretchable wearable sensors showed a high correlation with biomarkers in human blood and dynamically correlated with physiological activities. These results present routes to universal platforms for biomarker monitoring without the need for biofluid acquisition.

[Effects of oral exposure to iron oxide nanoparticles on reproductive system of male rats].

OBJECTIVE: To investigate the effects of oral exposure to iron oxide nanoparticles(Fe_2O_3NPs) on the reproductive system of male rats. METHODS: Forty male SD rats were randomly divided into control group and low, medium, high dose groups, 10 rats in each group, normal saline and 50, 100 and 200 mg/kg Fe_2O_3NPs suspension were given by gavage, respectively. The volume of gavage was 10 mL/kg for 28 days. The body weight was weighed every three days, and the body weight changes of rats were recorded. After intraperitoneal anesthesia with 10% chloral hydrate, the rats were sacrificed by cervical dislocation, and the testis and epididymis were collected. Weigh and calculate the testicular coefficient and epididymal coefficient, the pathological sections of rat testis were observed by hematoxylin-eosin staining, the number of epididymal sperm was counted under an optical microscope and the sperm deformity rate was calculated. The activities of acid phosphatase(ACP), alkaline phosphatase(AKP), lactate dehydrogenase(LDH) and γ-glutamyl transpeptidase(γ-GT), the activity of superoxide dismutase(SOD), and the contents of glutathione(GSH) and malondialdehyde(MDA) in rat testis homogenate were detected by kit method. RESULTS: Compared with control group, there was no significant difference in body weight, testicular coefficient and epididymal coefficient in each dose group. In the medium and high dose groups, the arrangement of spermatogenic epithelium was disordered and spermatogenic cells decreased. The number of sperm in high dose group was decreased, and the sperm deformity rate in medium and high dose groups was increased(P<0.01). The activity of ACP in medium and high dose groups increased(P<0.05), and the activity of γ-GT decreased(P<0.01). There was no significant change in the activity of AKP and LDH in testicular homogenate of rats in each group(P>0.05). The level of GSH in medium dose group was increased(P<0.05), and the content of MDA in medium and high dose groups was increased(P<0.01). There was no significant difference in SOD activity among the groups(P>0.05). CONCLUSION: Under the conditions of this experiment, Fe_2O_3NPs can cause damage to the structure of rat testicular tissue, reduce the number of sperm, increase the rate of sperm deformity, interfere with the activity of marker enzymes in testicular tissue and induce oxidative stress injury, which has a negative impact on the reproductive system of male rats.

Treat and extend regimen for diabetic macular oedema-a systematic review and meta-analysis.

PURPOSE: Various treatment regimens are currently practiced in the treatment of CI-DMO (centre-involving diabetic macular oedema). In recent years, there has been a growing body of evidence supporting a treat and extend (T&E) regimen for DMO which offers the promise of comparable visual and anatomical outcomes while reducing injection burden. This meta-analysis was hence performed to evaluate the aforementioned outcomes in the treatment of DMO. Ten studies met the inclusion criteria. METHODS: A search of PubMed, MEDLINE, Current Contents, and Cochrane Central Register of Controlled Trials (CENTRAL) databases was performed. We employed the terms 'treat AND extend AND (diabetic AND macular AND edema OR oedema)' to ensure a comprehensive search. The search workflow adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RESULTS: The pooled analysis of the mean number of injections in 1 year for T&E-aflibercept (AFL), T&E-ranibizumab (RBZ) and collectively was 9.1 (95% CI: 7.63-10.63), 10.0 (95% CI: 9.55-10.47) and 9.6 (95% CI: 8.62-10.49), respectively. Improvements in vision at 1 year for T&E-AFL, T&E-RBZ and collectively were 6.26 (95% CI: 3.24-9.29), 7.14 (95% CI: 4.76-9.52) and 7.08 (95% CI: 5.32-8.84) letters, respectively. The improvements in central subfield thickness at 1 year for T&E-AFL, T&E-RBZ and collectively were 131.94 (95% CI: 100.29-163.60), 108.64 (95% CI: 82.82-134.46) and 121.32 (95% CI: 102.89-139.75) microns, respectively. CONCLUSION: The meta-analysis of T&E for DMO did not show a clear advantage in reducing the number of injections compared to landmark clinical trials with pro-re-nata (PRN) treatment regimens in the first year of treatment with limited gains in visual and anatomical outcomes. However, the T&E approach offers the potential for fewer patient visits, thereby reducing treatment burden. Longer term studies on T&E with a standardised protocol would be required to assess the longevity of the vision gain in the first year despite a likely reduced treatment burden compared to the PRN trials.

Hyaluronidase-1-mediated glycocalyx impairment underlies endothelial abnormalities in polypoidal choroidal vasculopathy.

BACKGROUND: Polypoidal choroidal vasculopathy (PCV), a subtype of age-related macular degeneration (AMD), is a global leading cause of vision loss in older populations. Distinct from typical AMD, PCV is characterized by polyp-like dilatation of blood vessels and turbulent blood flow in the choroid of the eye. Gold standard anti-vascular endothelial growth factor (anti-VEGF) therapy often fails to regress polypoidal lesions in patients. Current animal models have also been hampered by their inability to recapitulate such vascular lesions. These underscore the need to identify VEGF-independent pathways in PCV pathogenesis. RESULTS: We cultivated blood outgrowth endothelial cells (BOECs) from PCV patients and normal controls to serve as our experimental disease models. When BOECs were exposed to heterogeneous flow, single-cell transcriptomic analysis revealed that PCV BOECs preferentially adopted migratory-angiogenic cell state, while normal BOECs undertook proinflammatory cell state. PCV BOECs also had a repressed protective response to flow stress by demonstrating lower mitochondrial functions. We uncovered that elevated hyaluronidase-1 in PCV BOECs led to increased degradation of hyaluronan, a major component of glycocalyx that interfaces between flow stress and vascular endothelium. Notably, knockdown of hyaluronidase-1 in PCV BOEC improved mechanosensitivity, as demonstrated by a significant 1.5-fold upregulation of Krüppel-like factor 2 (KLF2) expression, a flow-responsive transcription factor. Activation of KLF2 might in turn modulate PCV BOEC migration. Barrier permeability due to glycocalyx impairment in PCV BOECs was also reversed by hyaluronidase-1 knockdown. Correspondingly, hyaluronidase-1 was detected in PCV patient vitreous humor and plasma samples. CONCLUSIONS: Hyaluronidase-1 inhibition could be a potential therapeutic modality in preserving glycocalyx integrity and endothelial stability in ocular diseases with vascular origin.

Dysfunctional Autophagy, Proteostasis, and Mitochondria as a Prelude to Age-Related Macular Degeneration.

Retinal pigment epithelial (RPE) cell dysfunction is a key driving force of AMD. RPE cells form a metabolic interface between photoreceptors and choriocapillaris, performing essential functions for retinal homeostasis. Through their multiple functions, RPE cells are constantly exposed to oxidative stress, which leads to the accumulation of damaged proteins, lipids, nucleic acids, and cellular organelles, including mitochondria. As miniature chemical engines of the cell, self-replicating mitochondria are heavily implicated in the aging process through a variety of mechanisms. In the eye, mitochondrial dysfunction is strongly associated with several diseases, including age-related macular degeneration (AMD), which is a leading cause of irreversible vision loss in millions of people globally. Aged mitochondria exhibit decreased rates of oxidative phosphorylation, increased reactive oxygen species (ROS) generation, and increased numbers of mitochondrial DNA mutations. Mitochondrial bioenergetics and autophagy decline during aging because of insufficient free radical scavenger systems, the impairment of DNA repair mechanisms, and reductions in mitochondrial turnover. Recent research has uncovered a much more complex role of mitochondrial function and cytosolic protein translation and proteostasis in AMD pathogenesis. The coupling of autophagy and mitochondrial apoptosis modulates the proteostasis and aging processes. This review aims to summarise and provide a perspective on (i) the current evidence of autophagy, proteostasis, and mitochondrial dysfunction in dry AMD; (ii) current in vitro and in vivo disease models relevant to assessing mitochondrial dysfunction in AMD, and their utility in drug screening; and (iii) ongoing clinical trials targeting mitochondrial dysfunction for AMD therapeutics.

Impact of Microplastics on the Ocular Surface.

Plastics are synthetic materials made from organic polymers that are ubiquitous in daily living and are especially important in the healthcare setting. However, recent advances have revealed the pervasive nature of microplastics, which are formed by degradation of existing plastic products. Although the impact on human health has yet to be fully characterised, there is increasing evidence that microplastics can trigger inflammatory damage, microbial dysbiosis, and oxidative stress in humans. Although there are limited studies investigating their effect on the ocular surface, studies of microplastics on other organs provide some insights. The prevalence of plastic waste has also triggered public outcry, culminating in the development of legislation aimed at reducing microplastics in commercial products. We present a review outlining the possible sources of microplastics leading to ocular exposure, and analyse the possible mechanisms of ocular surface damage. Finally, we examine the utility and consequences of current legislation surrounding microplastic regulation.

Exploration of adaptation process and experience among the HIV/AIDS patients based on the comprehensive task-based adaptation model. / 基于综合任务模型探索HIV/AIDSæ‚£è€ çš„ç–¾ç— é€‚åº”è¿‡ç¨‹å’Œä½“éªŒ.

OBJECTIVES: Patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) confront multiple difficulties during the disease adaptation process. Based on the comprehensive task-based adaptation model, this study aims to explore the process and experience of adapting to living with HIV among HIV/AIDS patients and to provide evidence for promoting the adaptation of this population. METHODS: With the design of the phenomenon study, we purposefully recruited 43 HIV/AIDS patients and conducted semi-structural interviews. The qualitative data was analyzed by Van Manen method. RESULTS: There were 1 307 significant quotes and 6 themes with 14 sub-themes. "The shadow comes along with the sunshine" was proposed to describe the process of adapting to life with HIV. Another 5 themes emerged to represent the tasks as follows: the direction of the mental anchor, the management of physical tasks, social network and support, the occupational dilemma and benefits, and the consideration of the future. CONCLUSIONS: The adapting process possesses both common and personalized characteristics. Future intervention development should address the integrality and interaction of the adaptation tasks, contributing to the positive adaptation outcomes of HIV/AIDS patients.

Injectable Hybrid-Crosslinked Hydrogels as Fatigue-Resistant and Shape-Stable Skin Depots.

Injectable hydrogels have gained considerable attention, but they are typically mechanically weak and subject to repeated physiological stresses in the body. Herein, we prepared polyurethane diacrylate (EPC-DA) hydrogels, which are injectable and can be photocrosslinked into fatigue-resistant implants. The mechanical properties can be tuned by changing photocrosslinking conditions, and the hybrid-crosslinked EPC-DA hydrogels exhibited high stability and sustained release properties. In contrast to common injectable hydrogels, EPC-DA hydrogels exhibited excellent antifatigue properties with >90% recovery during cyclic compression tests and showed shape stability after application of force and immersion in an aqueous buffer for 35 days. The EPC-DA hydrogel formed a shape-stable hydrogel depot in an ex vivo porcine skin model, with establishment of a temporary soft gel before in situ fixing by UV crosslinking. Hybrid crosslinking using injectable polymeric micelles or nanoparticles may be a general strategy for producing hydrogel implants resistant to physiological stresses.

A nomogram for predicting survival of head and neck mucosal melanoma.

OBJECTIVES: We aimed to understand the clinical characteristics and better predict the prognosis of patients with mucosal melanoma of the head and neck (MMHN) using a nomogram. METHODS: Three hundred patients with nometastatic MMHN were included. Multivariable Cox regression was performed to analyze independent prognostic factors for overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS), and these factors were used to develop a nomogram. Concordance indexes (C-indexes), calibration plots, and receiver operating characteristic (ROC) analysis were performed to test the predictive performance of the nomogram in both the primary (n = 300) and validation cohorts (n = 182). RESULTS: The primary tumor site, T stage and N stage were independent risk factors for survival and were included in the nomogram to predict the 3- and 5-year OS, DFS, DMFS, and LRRFS in the primary cohort. The C-indexes (both > 0.700), well-fit calibration plots, and area under the ROC curve (both > 0.700) indicated the high diagnostic accuracy of the nomogram, in both the primary and validation cohorts. The patients were divided into three groups (high-risk, intermediate-risk, and low-risk groups) according to their nomogram scores. The survival curves of OS, DFS, DMFS, and LRRFS were well separated by the risk groups in both cohorts (all P < 0.001). CONCLUSIONS: The nomogram can stratify MMHN patients into clinically meaningful taxonomies to provide individualized treatment.

Meta-analysis of genome-wide association studies in multiethnic Asians identifies two loci for age-related nuclear cataract.

Age-related cataract is a leading cause of blindness worldwide, especially in developing countries where access to cataract surgery remains limited. Previous linkage and candidate gene studies suggested genetic influences on age-related nuclear cataract but few genetic markers have been identified thus far. We conducted genome-wide association studies on 4569 Asians (including 2369 Malays and 2200 Indians), and replicated our analysis in 2481 Chinese from two independent cohorts (1768 Chinese in Singapore and 803 Chinese in Beijing). We confirmed two genome-wide significant loci for nuclear cataract in the combined meta-analysis of four cohorts (n = 7140). The first locus was at chromosome 3q25.31 in KCNAB1 (rs7615568, fixed-effect Pmeta = 2.30 × 10(-8); random-effect Pmeta = 1.08 × 10(-8)). The second locus was at chromosome 21 in the proximity of CRYAA (rs11911275, fixed-effect Pmeta = 2.77 × 10(-8); random-effect Pmeta = 1.98 × 10(-9)), a major protein component of eye lens. The findings were further supported by up-regulation and down-regulation of KCNAB1 and CRYAA in human lens capsule, respectively, as the severity of nuclear cataract increases. The results offer additional insights into the pathogenesis of nuclear cataract in Asians.

Recent Progress in Using Biomaterials as Vitreous Substitutes.

Vitreous substitutes are crucial adjuncts during vitreo-retinal surgery for retinal diseases such as complicated retinal detachment, macular holes, complications of diabetic retinopathy, and ocular trauma involving posterior segment. In retinal detachment surgery, an internal tamponade agent is required to provide internal pressure for reattachment of the detached neurosensory retina. Current available options serve only as a temporary surgical adduct or short-term solution and are associated with inherent problems. Despite many years of intensive research, an ideal vitreous substitute remains elusive. Indeed, the development of an ideal vitreous substitute requires the concerted efforts of synthetic chemists and biomaterial engineers, as well as ophthalmic surgeons. In this review, we propose that polymeric hydrogels present the future of artificial vitreous substitutes due to its high water composition, optical transparency, and rheological properties that closely mimic the natural vitreous. In particular, thermosensitive smart hydrogels, with reversible sol to gel change, have emerged as the material class with the most potential to succeed as ideal vitreous substitutes, facilitating easy implementation during surgery. Importantly, these smart hydrogels also display potential as efficacious drug delivery systems.

Mitigating heavy metal accumulation in tobacco: Strategies, mechanisms, and global initiatives.

The threat of heavy metal (HM) pollution looms large over plant growth and human health, with tobacco emerging as a highly vulnerable plant due to its exceptional absorption capacity. The widespread cultivation of tobacco intensifies these concerns, posing increased risks to human health as HMs become more pervasive in tobacco-growing soils globally. The absorption of these metals not only impedes tobacco growth and quality but also amplifies health hazards through smoking. Implementing proactive strategies to minimize HM absorption in tobacco is of paramount importance. Various approaches, encompassing chemical immobilization, transgenic modification, agronomic adjustments, and microbial interventions, have proven effective in curbing HM accumulation and mitigating associated adverse effects. However, a comprehensive review elucidating these control strategies and their mechanisms remains notably absent. This paper seeks to fill this void by examining the deleterious effects of HM exposure on tobacco plants and human health through tobacco consumption. Additionally, it provides a thorough exploration of the mechanisms responsible for reducing HM content in tobacco. The review consolidates and synthesizes recent domestic and international initiatives aimed at mitigating HM content in tobacco, delivering a comprehensive overview of their current status, benefits, and limitations.

Polyurea-urethane Temperature-responsive Hydrogels for Sustained Delivery of Anti-VEGF Therapeutics.

Temperature-responsive hydrogels, or thermogels, have emerged as a leading platform for sustained delivery of both small molecule drugs and macromolecular biologic therapeutics. Although thermogel properties can be modulated by varying the polymer's hydrophilic-hydrophobic balance, molecular weight and degree of branching, varying the supramolecular donor-acceptor interactions on the polymer remains surprisingly overlooked. Herein, to study the influence of enhanced hydrogen bonding on thermogelation, we synthesized a family of amphiphilic polymers containing urea and urethane linkages using quinuclidine as an organocatalyst. Our findings showed that the presence of strongly hydrogen bonding urea linkages significantly enhanced polymer hydration in water, in turn affecting hierarchical polymer self-assembly and macroscopic gel properties such as sol-gel phase transition temperature and gel stiffness. Additionally, analysis of the sustained release profiles of Aflibercept, an FDA-approved protein biologic for anti-angiogenic treatment, showed that urea bonds on the thermogel were able to significantly alter the drug release mechanism and kinetics compared to usage of polyurethane gels of similar composition and molecular weight. Our findings demonstrate the unrealized possibility of modulating gel properties and outcomes of sustained drug delivery through judicious variation of hydrogen bonding motifs on the polymer structure.

Lutein Modulates Cellular Functionalities and Regulates NLRP3 Inflammasome in a H2O2-Challenged Three-Dimensional Retinal Pigment Epithelium Model.

Excessive hydrogen peroxide (H2O2) generated during retinal cell metabolic activity could lead to oxidative degeneration of retinal pigment epithelium (RPE) tissue, a specific pathological process implicated in various retinal diseases resulting in blindness, which can be mitigated by taking dietary antioxidants to prevent inflammation and impaired cellular dysfunction. This study tested the hypothesis that damages induced by oxidative stresses can be mitigated by lutein in a H2O2-challenged model, which was based on an ARPE-19 cell monolayer cultured on three-dimensional (3D)-printed fibrous scaffolds. Pretreating these models with lutein (0.5 µM) for 24 h can significantly lower the oxidative stress and maintain phagocytosis and barrier function. Moreover, lutein can modulate the NLRP3 inflammasome, leading to a ∼40% decrease in the pro-inflammatory cytokine (IL-1ß and IL-18) levels. Collectively, this study suggests that the 3D RPE model is an effective tool to examine the capability of lutein to modulate cellular functionalities and regulate NLRP3 inflammation.

Highly drug/target-tolerant neutralizing antibody (NAb) assay development through target-based drug depletion and drug-based NAb extraction for an anti-EGFR therapeutic monoclonal antibody.

The reduction of immunogenicity is fundamental for the development of biobetter Erbitux, given that the development of an immune response reduces treatment efficacy and may lead to potential side effects. One of the requirements for the clinical research of a Erbitux biobetter candidate (CMAB009) is to develop a neutralizing antibody (NAb) assay, and sufficient drug and target tolerance for the assay is necessary. Here, we describe the development of a competitive ligand binding (CLB) assay for CMAB009 with high drug and target tolerance through target-based drug depletion and drug-based NAb extraction, the integrated experimental strategy was implemented to simultaneously mitigate drug interference and enhance target tolerance. Following troubleshooting and optimization, the NAb assay was validated for clinical sample analysis with the sensitivity of 92 ng/mL, drug tolerance of 70 µg/mL and target tolerance of 798 ng/mL. The innovative drug depletion and NAb extraction achieved though the combination of drug and target beads would enable the development of reliable NAb assays for many other therapeutics that overcome drug and its target interference for more precise and sensitive NAb assessment.

Rationale and protocol paper for the Asia Pacific Network for inherited eye diseases.

PURPOSE: There are major gaps in our knowledge of hereditary ocular conditions in the Asia-Pacific population, which comprises approximately 60% of the world's population. Therefore, a concerted regional effort is urgently needed to close this critical knowledge gap and apply precision medicine technology to improve the quality of lives of these patients in the Asia-Pacific region. DESIGN: Multi-national, multi-center collaborative network. METHODS: The Research Standing Committee of the Asia-Pacific Academy of Ophthalmology and the Asia-Pacific Society of Eye Genetics fostered this research collaboration, which brings together renowned institutions and experts for inherited eye diseases in the Asia-Pacific region. The immediate priority of the network will be inherited retinal diseases (IRDs), where there is a lack of detailed characterization of these conditions and in the number of established registries. RESULTS: The network comprises 55 members from 35 centers, spanning 12 countries and regions, including Australia, China, India, Indonesia, Japan, South Korea, Malaysia, Nepal, Philippines, Singapore, Taiwan, and Thailand. The steering committee comprises ophthalmologists with experience in consortia for eye diseases in the Asia-Pacific region, leading ophthalmologists and vision scientists in the field of IRDs internationally, and ophthalmic geneticists. CONCLUSIONS: The Asia Pacific Inherited Eye Disease (APIED) network aims to (1) improve genotyping capabilities and expertise to increase early and accurate genetic diagnosis of IRDs, (2) harmonise deep phenotyping practices and utilization of ontological terms, and (3) establish high-quality, multi-user, federated disease registries that will facilitate patient care, genetic counseling, and research of IRDs regionally and internationally.

Effect of xanthophyll-rich food and supplement intake on visual outcomes in healthy adults and those with eye disease: a systematic review, meta-analysis, and meta-regression of randomized controlled trials.

CONTEXT: Xanthophyll intake is known to improve eye health; however, its benefits on visual outcomes have not been systematically studied, particularly in a population with eye diseases. OBJECTIVE: A systematic review, meta-analysis, and meta-regression were conducted to investigate the effect of xanthophyll intake on visual outcomes, and further subgroup analysis was performed on the basis of eye disease status. DATA SOURCES: The PubMed, Scopus, Embase, CINAHL, Cochrane, and Web of Science databases were searched, and relevant randomized controlled trials were identified. DATA EXTRACTION: For systematic review, meta-analysis, and meta-regression, 43, 25, and 21 articles were selected, respectively. DATA ANALYSIS: Xanthophyll intake enhanced macular pigment optical density (MPOD) for both heterochromatic flicker photometry (weighted mean difference [WMD], 0.05; 95% confidence interval [CI], 0.03-0.07) and autofluorescence imaging (WMD, 0.08; 95%CI, 0.05-0.11) measurements and decreased photostress recovery time (WMD, -2.35; 95%CI, -4.49 to -0.20). While enhancement in visual acuity logarithm of the minimum angle of resolution was observed in response to the xanthophyll-rich food and supplement intake only for patients with eye disease (WMD, -0.04; 95%CI, -0.07 to -0.01). Meta-regression showed a positive correlation between change in MPOD (heterochromatic flicker photometry) and the corresponding change in serum lutein levels (regression coefficient = 0.068; P = 0.00). CONCLUSION: Intake of xanthophyll-rich food or supplements can improve eye health. Additional improvement in visual acuity was observed in patients with eye disease. A positive association between MPOD and serum lutein level, while absent with dietary xanthophyll intake, suggests the importance of bioavailability when examining the effect of xanthophyll on eye health. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42021295337.

Reply to Finsterer et al.

This letter acknowledges Finsterer and colleagues' insightful comments on pesticide use in fruits and vegetables and impact on eye health. Pesticides can harm eyes through various exposures. Adverse effects occur due to direct entry into ocular tissues, with absorption through eye components. While the potential of organic diets to reduce pesticide exposure is acknowledged, the original paper's cited studies lack clarity on whether organic diet interventions were used. Future systematic reviews comparing organic and nonorganic diets could provide further insights.

Impacts of regular consumption of grapes on macular pigment accumulation in Singapore older adults: a randomized controlled trial.

Background: Oxidative stress is a key risk factor for visual impairment and consuming dietary antioxidant-rich foods may help in managing visual impairments. However, a limited number of studies have investigated the effect of dietary antioxidant-rich food including grapes on eye health in older adults. Objectives: To assess the effects on macular pigment accumulation of regular consumption of grapes in Singapore older adults. Methods: This was a 16 week, double-blind, randomized, placebo-controlled trial. Thirty-four Singapore older adults were randomized into regularly consuming either 46 g day-1 of freeze-dried table grape powder (the intervention group) or the same amount of placebo powder (the control group). Macular pigment optical density (MPOD), skin carotenoid status, advanced glycation end product (AGEs) status and dietary lutein intake were assessed every 4 weeks, and plasma lutein concentration, total antioxidant capacity and total phenolic content were measured every 8 weeks. Results: A significant time effect (p = 0.007) was observed for MPOD, and this is largely attributed to the improvement in the MPOD for the intervention group, as a significant increase was observed only in this group (week 0: 0.56 ± 0.04 D.U.; week 16: 0.61 ± 0.04 D.U., p < 0.01). Additionally, a significant increase in plasma total antioxidant capacity (week 0: 0.26 ± 0.13 mM TEAC; week 16: 0.36 ± 0.20 mM TEAC, p < 0.01) and total phenolic content (week 0: 10.50 ± 0.44 mg L-1 GAE; week 16: 12.58 ± 0.55 mg L-1 GAE, p < 0.001) was observed for the intervention group only. In contrast, a significant increase in skin AGE status was observed in the control group (week 0: 2.47 ± 0.24; week 16: 2.99 ± 0.12, p < 0.05) while this was mitigated in the intervention group. There were no differences in dietary lutein intake, plasma lutein concentration and skin carotenoid status between groups throughout the study. Conclusions: Regular intake of grapes may improve eye health in Singapore older adults, specifically in augmenting MPOD, which can be explained by an increase in plasma total antioxidant capacity and phenolic content, and the downregulation of AGEs. This study was registered at clinicatrials.gov as NCT05064865.