bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling senescence in ARPE19 cells to investigate the role of small extracellular vesicles in age‐related macular degeneration
Authors: Fernandes Rosa , Correia Diana , Martins Beatriz , Malva João , Girão Henrique 
Published: January 2025

Aims/Purpose: Age‐related macular degeneration (AMD) is a degenerative disease causing significant vision loss in the elderly. The molecular mechanisms of AMD onset and progression are not fully understood. Senescent cells are known to secrete increased amounts of small extracellular vesicles (sEV). However, the impact of sEVs on RPE dysfunction and AMD through senescence spreading remains unclear. Our study aimed to develop an in vitro model of RPE cell senescence.Methods: We used the retinal pigment epithelial cell line, ARPE‐19. Senescence induction in RPE cells was achieved through two different approaches: repeated passaging (replicative senescence) and ionizing radiation (DNA damage‐induced senescence). Characterization of sEVs released by RPE cells was performed and markers of senescence were assessed.Results: RPE cells subjected to replicative exhaustion or ionizing radiation showed higher H2AX foci accumulation compared to p9 cells. Ionizing radiation significantly increased nucleus area and deformation, with a similar trend at p21 and p31. Levels of p21, critical for establishing senescence, increased at p31 and showed a tendency to rise in ionizing radiation‐exposed cells. Levels of p16, maintaining the senescence phenotype, also increased in ionizing radiation‐exposed cells and tended to rise at p21 and p31. Activities of active MMP‐2 and ‐9 increased in the conditioned medium of senescent cells, with MMP‐2 activity correlating with higher protein levels. sEVs from senescent cell‐conditioned medium showed significant increases in concentration and mean size compared to p9 cells.Conclusions: We successfully induced senescence in ARPE19 cells, creating a valuable model to investigate the role of sEVs in spreading senescence to neighboring cells, especially in the context of AMD onset.Support: FCT, Portugal: 2020.04811.BD; PEst UIDB/04539/Base/2020 and UIDP/04539/Programatico/2020.European Union's Horizon 2020 Teaming project MIA‐Portugal (no 857524) and CHAngeing – Connected Hubs in Ageing: Healthy Living to Protect Cerebrovascular Function (no 101087071), funded by Excellence Hubs Call – Horizon‐ WIDERA‐2022‐ACCESS‐04‐01.
To what extend cataract surgery changes perceptual functions?
Authors: Garobbio Simona , Hall Ursula , Zuche Hanna , Herzog Michael 
Published: January 2025

Aims/Purpose: Cataract, i.e., an opacification of the natural intraocular lens, is one of the leading causes of visual impairments worldwide. Cataract surgery, which involves the removal of the opaque lens and implantation of an artificial intraocular lens, is one of the most cost‐efficient interventions in all of health care to improve visual impairments. However, it remains unclear how exactly visual performance changes after surgery, which we aim to investigate in our study.Methods: We tested 30 older adults undergoing cataract surgery longitudinally with a battery of visual tests. Participants were tested a total of four times: before surgery, after surgery on one eye, after surgery on the second eye, and a few weeks after surgery when vision was fully stabilized. The battery tested various visual abilities and included the following tests: visual acuity, contrast sensitivity, coherent motion, orientation discrimination, reaction time, and visual search. All tests were performed binocularly, and a subset of tests was repeated monocularly.Results: Results suggest that visual acuity and orientation discrimination performance increase after each surgery. Performance in contrast sensitivity and coherent motion significantly increases after the surgery on the first eye but not between the second and third tests. Thus, monocular surgery is sufficient to improve performance in these tests. On the other side, visual search and reaction time performance do not seem to benefit from cataract surgery. For all tests, the level of performance after surgery is maintained in the last testing.Conclusions: Our study shows that cataract surgery leads to improved perceptual functions in most, but not all, tests. Future analysis will determine whether the level of performance change depends on baseline performance, and whether predictions about surgery success can be made based on performance in the tests.
Visual acuity outcomes by age at symptom onset in the natural history of leber hereditary optic neuropathy: Analysis of historical data from Case Record Survey‐2 (CRS‐2)
Authors: Llòria Xavier , Yu‐Wai‐Man Patrick , van Everdingen Judith , Leroy Bart , Krawczynski Maciej , Lamperti Costanza , Carelli Valerio , Klopstock Thomas 
Published: January 2025

Aims/Purpose: The clinical progression of Leber hereditary optic neuropathy (LHON) is thought to be influenced by the age at symptom onset. The Case Record Survey‐2 (CRS‐2; NCT02796274) aimed to establish the natural history of LHON in idebenone‐naïve patients. Here, we report 12‐month clinical outcomes by age at symptom onset.Methods: Data were extracted from case records (20 sites, 7 European countries) meeting the following criteria: aged ≥12 years, m.11778G > A, m.3460G > A or m.14484T > C mitochondrial DNA mutation, onset of symptoms (OoS) after 1999 and ≥2 visual acuity assessments (VAA) within 5 years of OoS. Baseline (BL) was defined as the first VAA after OoS. Spontaneous clinically relevant benefit, recovery, stabilisation and worsening (sCRB, sCRR, sCRS and sCRW, respectively) were calculated as previously described.1 Eyes eligible for analysis had a VAA 12±3 months from BL and were stratified according to age at OoS ( < 15, 15–35 and > 35 years).Results: A total of 21, 42 and 44 eyes were eligible for the 12‐month analysis in those aged < 15, 15–35 and > 35 years at OoS, respectively.Greater sCRB rates were observed in eyes aged < 15 years at OoS (42.9%, 9/21) compared to eyes aged 15–35 years (19.0%, 8/42), and > 35 years (15.9%, 7/44). This was largely driven by higher sCRS rates ( < 15 years: 54.5%, 6/11; 15–35 years: 28.6%, 4/14; > 35 years: 15.8%, 3/19). Higher sCRR rates ( < 15 years: 19.0%, 4/21; 15–35 years: 11.9%, 5/42; > 35 years: 11.4%, 5/44) and lower sCRW rates ( < 15 years: 47.4%, 9/19; 15–35 years: 85.7%, 24/28; > 35 years: 60.0%, 21/35) were also observed in eyes aged < 15 years.Conclusions: Better clinical outcomes were observed in eyes aged < 15 years at OoS in CRS‐2, consistent with previous reports. Outcomes did not markedly differ between eyes with OoS between 15–35 years and > 35 years. The CRS‐2 study offers important insights into the impact of age on the natural history of LHON.References1. Yu‐Wai‐Man P, et al. Cell Rep Med. 2024;5:101437.
Vision‐related quality of life of myopic children using combination treatment: Atropine and defocus‐incorporated multiple segment spectacle lenses
Authors: Villahoz Noemi Guemes , Hernandez‐Garcia Elena , Gomez‐de‐Liano C. Nunila , Porras‐Angel Paloma , Bella‐Gala Rafael , Talavero‐Gonzalez Paula , Ruiz‐Pomeda Alicia , Martin‐Garcia Beatriz , Shah Rakhee , Feijoo Julian Garcia , Gomez‐de‐Liano Rosario 
Published: January 2025

Purpose: To assess vision‐related quality of life (VR‐QoL) in children undergoing myopia control treatment with atropine compared to children treated with combination treatment of atropine and Defocus incorporated multiple segments (DIMS) spectacle lenses.Methods: Longitudinal study that included myopic children aged 4 to 16 years undergoing myopia control treatment. Group A included children on 0.025% atropine eyedrops and single‐vision lenses, and group B included children on combined treatment of 0.025% atropine and DIMS lenses. Demographic and clinical data, including cycloplegic spherical equivalent refraction (SER) and axial length (AL), were noted. VR‐QoL was assessed using the Children's Visual Function questionnaire (CVFQ) and the Pediatric Eye Questionnaire (PedEyeQ) before initiating and after 6 months of treatment. Statistical analyses (Mann‐Whitney U‐test or t‐test) were performed.Results: 95 patients were included: 50 children in group A, mean age 8.94 ±2.50 years and 45 children in group B, mean age 9.51 ±2.46 years (p = 0.266). No significant differences were found in the overall VR‐QoL between both groups with PedEyeQ. Functional Vision and Social item scores (PedEyeQ) significantly improved at the 6M follow‐up in group A (p = 0.03 and p = 0.016, respectively) and group B (all p = 0.01). Scores on the Eye Condition item (PedEyeQ) at baseline and at 6M follow‐up were reversed; a decrease in group A, 89.73 [69.86‐89.73] and 64.98 [50.02‐74.99] (p < 0.01), and an increase in group B, 69.96 [69.96‐89.72] and 74.97 [43.62‐85] (p = 0.039). For the CVFQ, only Group B showed an improvement in General Vision (p = 0.049) and Competence (p = 0.031) scores.Conclusions: Myopic children treated with atropine and those using combination treatment (atropine and DIMS) do not seem to have significant differences in overall VR‐QoL following 6 months of treatment. General Vision (CVFQ), Competence (CVFQ) and Eye Condition (PedEyeQ) scores improve significantly for children on combination treatment.
Retinal oxygen extraction during systemic hypoxia assessed with laser‐speckle flowgraphy and retinal oximetry
Authors: Pai Viktoria , Lindner Theresa , Janku Patrick , Schmetterer Leopold , Schmidl Doreen , Garhöfer Gerhard 
Published: January 2025

Aims/Purpose: Retinal oxygen extraction has been found to be altered in several ocular and systemic diseases, such as diabetic retinopathy, glaucoma or neurodegenerative diseases. However, measurement techniques for the assessment of retinal oxygen extraction are limited because most of them are based on time‐consuming and custom‐built devices. In the present pilot study, we assessed retinal oxygen extraction during systemic hypoxia with a combination of two commercially available devices: Laser‐Speckle Flowgraphy (LSFG) and retinal oximetry.Methods: Retinal blood flow and retinal oxygen saturation were measured in each vessel around the optic nerve head at the same position. Arterial and venous oxygen content was estimated from the measured retinal oxygen saturation parameters and the difference between these two parameters was calculated (cO2,DIFF). By using mean vessel flow rate (MV) for retinal blood flow and cO2,DIFF, retinal oxygen extraction was determined. For each healthy study participant, baseline measurement and measurement during inhalation of 88% nitrogen in 12% oxygen were performed.Results: Ten (10) healthy subjects (4 females, 6 males) with a mean age of 27 ± 3 years were included in this study. During systemic hypoxia, a significant decrease in arterial oxygen content occurred (p = 0.046) while venous oxygen content did not change, leading to a decrease in cO2,DIFF. As expected, this was accompanied by a significant increase in MV (p = 0.014). No change in retinal oxygen extraction was observed (46 ± 8 a.u. at baseline vs. 46 ± 5 a.u. during hypoxia, p = 0.997).Conclusions: Breathing of 88% nitrogen in 12% oxygen caused a significant decrease in retinal arterial oxygen content. This was compensated by an increase in retinal blood flow in order to keep retinal oxygen extraction constant. This was physiologically expected, and these findings are consistent with the literature. Therefore, the presented approach for measurement of retinal oxygen extraction appears to be feasible.
Early detection of biochemical changes in tear fluid induced by contact lens wear using Raman spectroscopy
Authors: Tavazzi Silvia , Pezzoli Fabio , Ponzini Erika , Duse Alessandro 
Published: January 2025

Aims/Purpose: The aim of this study is to evaluate different approaches to investigate early alterations in tear biomolecular profiles induced by contact lens (CL) wear. This includes assessing the impact of CL wear on tear volume, osmolarity, and biomolecular composition using Raman spectroscopy.Methods: Two participants of the same sex (male), age (23 years), and with a similar lifestyle wore different CLs for two hours. Ocular analysis was performed at three time points: before CL insertion, immediately after CL removal, and two hours post‐removal. The analyses included tear meniscus height and osmolarity measurements. Tear samples were collected at each time point and analyzed using Raman spectroscopy.Results: Tear volume and osmolarity remained unchanged throughout the study. Raman spectroscopy highlighted notable changes in the biomolecular profile of tears after CL wear, particularly in the 2700‐3200 cm‐¹ spectral window.Conclusions: Among the analyses performed, only Raman spectroscopy revealed significant changes. It highlighted alterations in the biomolecular profile of tears post‐CL wear, particularly in the 2700‐3200 cm‐¹ spectral window associated with C‐H stretching. The ability of Raman spectroscopy to detect these subtle, subclinical changes underscores its value as a non‐invasive tool for analyzing individual responses to CLs. Notably, Raman spectroscopy captures molecular‐level alterations, which form the basis of changes in the physical and functional properties of the tear film, including those measured by tear meniscus height and osmolarity. These changes become detectable by traditional techniques only in a late stage, while molecular‐level alterations can be detected earlier, providing an opportunity for proactive intervention and management.
Metabolomics reveals pathophysiological mechanisms of proliferative diabetic retinopathy progression
Authors: Mansikkaviita Jannika , Korhonen Ani , Finell Johan , Loukovaara Sirpa , Nieminen Anni 
Published: January 2025

Aims/Purpose: Diabetic retinopathy (DR) is a common, sight‐threatening microvascular complication of diabetes. The end‐stage form of the disease, proliferative DR (PDR), is characterized by ischemia and inflammation‐induced pathological neovascularization at the vitreoretinal interface, often accompanied by vitreous hemorrhage and tractional retinal detachment (TRD). The mechanisms behind the progression of PDR, and the effect of different treatments on these processes, are not fully understood. As the number of diabetics is on the rise, and current treatment options are invasive and limited in their efficacy, the search for novel targets for treatment and prevention of PDR progression is crucial.The aim of our study is to reveal differences between vitreous metabolite profiles of non‐PDR and PDR disease states, and the effect of treatment on those profiles. We aim to better understand the progression of the disease and to identify potential target metabolites and pathways.Methods: We analyzed metabolites in vitreous samples from type II diabetic patients with different stages of DR (non‐PDR patients, PDR patients, and PDR patients with TRD) via targeted LC‐MS metabolomics. Pathway enrichment analyses were performed using MetaboAnalyst 5.0.Results: We identified various significantly altered metabolites such as deoxycarnitine, indole‐3‐acetic acid and glycine between non‐PDR and PDR patients. Metabolite enrichment analyses revealed strong associations with, for example, tryptophan and glycine metabolism.Conclusions: We identified metabolites, processes and metabolic pathways of interest in PDR progression in type II diabetic patients, some of which could be potentially useful for development of novel treatment options. Furthermore, this metabolic information provides new insight into pathogenetic mechanisms behind PDR progression.
The cumulative impact of air pollution on dry eye disease: Evidence from the Korea National Health and Nutrition Examination Survey (2017–2020)
Authors: Shin Dong Weon , Cho Yunnie , Rim Tyler , Seo Kyung Yul 
Published: January 2025

Aims/Purpose: This study investigated the relationship between environmental pollution and dry eye disease (DED), focusing on the cumulative impact of air pollutants.Methods: Cross‐sectional data from the 7th and 8th Korea National Health and Nutrition Examination Survey (KNHANES) (2017‐2020) were analyzed alongside air pollution data from the National Ambient Air Quality Management Information System (NAMIS). Non‐smokers aged between 40 and 80 were selected (n = 8,840). The daily cumulative index (CI) of air quality was calculated for each region of residence based on key pollutants, including SO₂, NO₂, PM2.5, and PM10. Using Gaussian mixture models, each day was categorized as usual, poor, or bad based on CI values. Multiple logistic regression analysis assessed the impact of air pollutants on DED while accounting for clinical, demographic, and meteorological factors. Additionally, the Aggregated Air Quality Index (AAQI) was calculated and evaluated for the same dataset.Results: Multiple logistic regression analysis indicated that the proportion of high pollution days within a year significantly increased the odds of DED (OR: 4.19, 95% CI: 1.23–14.25, p = 0.02), after adjusting for factors associated with DED as covariates. Although the AAQI did not show statistical significance, the Cumulative Index effectively demonstrated the aggregated effect of multiple air pollutants on DED.Conclusions: This research highlights the utility of a model using regularly measured air quality indicators, providing a comprehensive assessment of the aggregated effect of air pollutants. Implementing these measures can help identify at‐risk populations and consider environmental factors in managing and preventing DED.References: Saxena, A., & Shekhawat, S. (2017). Ambient Air Quality Classification by Grey Wolf Optimizer Based Support Vector Machine. Journal of environmental and public health, 2017, 3131083. Kyrkilis, G., Chaloulakou, A., & Kassomenos, P. A. (2007). Development of an aggregate Air Quality Index for an urban Mediterranean agglomeration: relation to potential health effects. Environment international, 33(5), 670–676.
Studies in the electroretinogram I‐wave: Evidence for off pathway origin and association with a myopia risk locus
Authors: Vetrivel Krishnika , Tan Jit Kai , Xu Zihe , Jiang Xiaofan , Leo Shaun , Bhatti Taha , Tariq Ambreen , Hammond Christopher , Hysi Pirro , Mahroo Omar 
Published: January 2025

Aims/Purpose: A myopia‐risk locus near the GJD2 gene has been associated with cone‐driven electroretinograms (ERGs), specifically cone‐driven OFF pathway signals. In light‐adapted ERGs to a standard flash, conventionally measured components are the a‐wave and b‐wave. A later component, the “i‐wave”, is thought to originate in retinal OFF pathways, as evidenced by pharmacological experiments in primates. We investigated this component in human ERGs, testing the hypothesis that an association would be found with the myopia risk locus.Methods: ERGs were examined from patients with rare monogenic post‐phototransduction deficits affecting only ON pathways, or both ON and OFF pathways, to explore which gave rise to the i‐wave. ERGs were then analysed from genotyped healthy adults from the TwinsUK cohort. The i‐wave amplitude was measured in the standard flash ERG by two investigators independently. We investigated association with allelic identity, adjusting for age, sex and inter‐individual relatedness. Separately, we adjusted for refractive error where this was available.Results: Patient recordings showed i‐waves persisted in absence of ON pathway signals, but were abolished when both ON and OFF pathways were impaired. Recordings and genotypes were available in 184 TwinsUK individuals (95% female). Mean (SD) age was 64.1 (9.7) years. Allelic dosage at the risk locus was significantly associated with i‐wave amplitude Refractive error was available for 175 participants. The association in these individuals remained significant both before and after adjusting for refractive error (p = 0.035 and p = 0.043 respectively).Conclusions: ERGs in patients are consistent with the human i‐wave arising from cone‐driven OFF pathways. i‐wave amplitudes associated significantly with allelic dosage at the myopia risk locus. This supports importance of cone‐driven signalling in myopia development and adds evidence that this locus affects cone‐driven OFF pathway signals.
Patient demographics and surgical outcomes of dropped nucleus in cataract surgery
Authors: Martins Pedro , Cabanas João , Cardoso Daniel , Sousa‐Neves Filipe 
Published: January 2025

Aims/Purpose: To analyse the baseline demographic/clinical characteristics and visual outcomes of patients who experienced nucleus drop during cataract surgery with subsequent need for pars plana vitrectomy (PPV).Methods: Retrospective case series of patients who underwent phacoemulsification for non‐traumatic cataract and experienced nucleus drop during surgery, with subsequent need for PPV to extract the dropped fragments. Demographic data, ocular comorbidities (such as ocular hypertension – OHT/glaucoma, pseudoexfoliation – PEX, presence of advanced white or brunescent cataract, shallow anterior chamber or previous intravitreal injections – IVI), timing of nucleus drop, intraoperative complications and post PPV visual outcomes and complications, for the study period (2018 to 2023), were collected.Results: Over the study period 33 eyes of 33 patients experienced nucleus drop. 17 (52%) were male with a mean age of 74.4±9.4 (45‐92) years. Pre‐operative visual acuity ranged from light perception to 0.22 logmar. Three patients (9.1%) had previously undergone IVI and 7 (21.2%) had glaucoma or OHT; 9 (27.3%) had PEX ‐ all but one had poor pupillary dilation ( < 5 mm). A significant proportion of patients (13, 40.4%) presented with advanced brunescent/white cataracts. Most nucleus drops occurred following a posterior capsular rupture during quadrant removal (18 cases – 54.5%) or hydro‐dissection (8 cases – 24.3%); remaining cases occurred following a radialized capsulorhexis with posterior extension or due capsular bag‐nucleus luxation to the vitreous. PPV was uneventful in most cases – one patient developed an epiretinal membrane 2 years after PPV. Visual acuity improved by an average of ‐0.96 logmar in the post‐operative period.Conclusions: PPV is the preferred management for nucleus drop after complicated cataract surgery. Current devices and surgeon expertise allow for a low risk of complications and good visual/anatomical outcomes.
Adipose‐derived mesenchymal stem cells (ADMSCS) and retinal pigment epithelial cells (RPE‐1) interactions in stress environments via tunneling nanotubes
Authors: Gozel Merve , Senkoylu Karya , Kesim Cem , Hasanreisoğlu Murat 
Published: January 2025

Aims/Purpose: The study aims to elucidate the potential role of TNT‐mediated intercellular communication between the AdMSCs and RPE‐1 cells in reducing stress‐induced damage.Methods: Oxidative stress and serum starvation were used as stress to create TNTs between the AdMSC and RPE‐1 cells. Immunofluorescence and scanning electron microscopy were used to show that TNT formation. Following stress conditions, the cells' viability was examined by CTG assay, and the levels of reactive oxygen species (ROS) were measured by H2DCFH‐DA probes. Microscopy showed that JC‐1 labelled mitochondrial exchange occurs between cells via TNTs. To prevent TNTs, a transmembrane culture system was used and evaluated how to effect on cell viability and changes of ROS levels.Results: We examined how TNTs support mitochondrial transport and intercellular communication between AdMSCs and RPE‐1 during stress. We discovered that TNT‐mediated mitochondrial translocation from AdMSCs to RPE‐1 contributes to both increased cell survival and a decrease in ROS levels. We showed that AdMSCs and RPE‐1 had a direct connection that was essential for stress recovery. After stress‐induced damage, co‐culture improved vitality and maintained retinal function. Because mechanical restriction of TNT synthesis reduced cell viability and raised ROS levels, it is clear that TNTs are essential for cellular defence.Conclusions: Overall, our study provides valuable insights into the cellular mechanisms underlying stress response and underscores the therapeutic promise of AdMSC derived TNTs in preserving retinal health.