bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advancing in vivo modelling and delivery systems for triplet repeat expansion‐mediated corneal endothelial dystrophy: Implications in Anti‐miR therapy
Authors: Piqueras‐Losilla Diego , Campillo Isabel , Perea‐Galera Laura , López‐Domènech Sandra , Rocha‐Barajas Milagros , Roig‐Revert Maria Jose , Peris‐Martinez Cristina , Barbera‐Fuset Clara , Huguet Aline , Gourdon Genevieve , Llamusí Beatriz , Cerro‐Herros Estefanía 
Published: January 2024

Aims/Purpose: Triplet repeat expansion‐mediated endothelial corneal dystrophy, including Fuchs endothelial corneal dystrophy (FECD), is characterized by abnormal expansions of trinucleotide repeats, resulting in corneal endothelium dysfunction [1,2]. This study aims to characterize a reliable in vivo model, that it lacks, and explore the therapeutic potential of anti‐miRs, which have shown efficacy in other disorders involving triplet repeat expansions [3,4,5]. Current invasive delivery methods for eye‐based treatments present challenges, so our focus is on optimizing non‐invasive delivery methods for anti‐miR‐based therapy.Methods: A transgenic mouse model with a significant CTG repeat expansion (>1000), established in DM1, was investigated as an in vivo model for corneal endothelial dystrophy. The Fuchs‐like phenotype of the disease was characterized using immunohistochemistry and FISH techniques. Delivery methods were explored to enhance the targeting of corneal endothelial cells (CEC). Delivery efficacy and marker expression were assessed using fluorescence, RT‐qPCR, PCR, western blotting, and immunocytochemistry techniques. FECD cell cultures were established to evaluate the challenging FECD‐specific delivery systems.Results: A novel in vivo model has been characterized for studying corneal endothelial dystrophy caused by triplet repeat expansion, exhibiting similarities to the Fuchs‐like phenotype. Enhanced delivery methods have been identified to improve transfection efficiency in endothelial (HUVEC) and CEC. Successful establishment of FECD cell cultures has allowed the evaluation of these enhanced delivery systems.Conclusions: The first successful characterization of an in vivo model for triplet repeat expansion‐mediated corneal endothelial dystrophy has been achieved. This model shows potential for assessing the reversal of these phenotypes in the ocular region. Moreover, the successful delivery of new systems across CEC suggests the possibility of non‐invasive administration of anti‐miR directly into the eye. This breakthrough opens the door for future research on anti‐miRs in other diseases caused by triplet repeat expansion, such as FECD.ReferenceIn PMID: [1] 28886202, [2] 34130750, [3] 29946070, [4] 32805487, [5] 22764244.
Vitamin D supplementation reduces systemic modulation of oxidative stress and collagen degradation in keratoconus patients
Authors: Suanno Giuseppe , Vitar Romina Mayra Lasagni , Fonteyne Philippe , Knutsson Karl Anders , Bertuzzi Federico , Galli Laura , Rama Paolo , Ferrari Giulio 
Published: January 2024

Aims/Purpose: To assess whether vitamin D (Vit D) supplementation modulates systemic biomarkers involved in collagen degradation and oxidative stress in adolescent patients affected with keratoconus (KC).Methods: This study included forty adolescent patients (age range: 16–19 years) with KC and Vit D insufficiency (<30 ng/mL). The patients were supplemented with vitamin D for 6 months and followed up for additional 6 months (total study duration: 12 months). Blood samples were collected at 1, 6, and 12 months. The levels of Vit D or its receptor (VDR), collagen catabolism (type I collagen degradation product; ICTP), and oxidative stress (Peroxisome proliferator‐activated receptor gamma; PPAR‐γ) were quantified by ELISA or RT‐PCR.Results: We found that Vit D levels significantly increased at 6 months after supplementation. Moreover, at month 6 the expression of VDR was upregulated (p < 0.01), while collagen degradation (ICTP; p < 0.01) and oxidative stress (PPAR‐γ; p < 0.05) were significantly reduced.Conclusions: Our findings show that Vit D supplementation reduces oxidative stress and collagen catabolism, which have a key role in KC pathophysiology. These findings provide a potential mechanism by which Vit D could impact KC progression and provide preliminary evidence that KC may be a systemic disease.
Investigation of genes and miRNAs associated with scarless healing in orbital adipose‐derived and limbal‐derived mesenchymal stem cells treated with vitamin C
Authors: Atalay Eray , Eyubova Sevinj , Soykan Merve Nur , Tasa Burcugül Altuğ , Ozalp Onur , Sarıboyacı Ayla Eker 
Published: January 2024

Aims/Purpose: In this study we aimed to investigate miRNAs associated with scarless wound healing in limbal‐derived stomal‐mesenchymal stem cells (hLMSC) and orbital adipose tissue‐derived stem cells (hOA‐MSC) treated individually with vitamin C and exosomes obtained after vitamin C treatment.Methods: Isolation and characterization of hLMSCs and hOA‐MSCs were performed. MTT assay was employed to determine the ideal non‐cytotoxic and proliferative concentration of vitamin C (vit C). The selected concentration was applied to the cell culture medium of hLMSCs and hOA‐MSCs (vit C‐treated) followed by procurement of secreted exosomes (vit C‐exo) and their characterization. These exosomes were then used to enrich cell culture media of naïve hLMSCs and hOA‐MSCs. miR29, miR107, miR155, and miR543 miRNAs and Transforming Growth Factor Beta 1 (TGFβ1), TGFβ3 were analysed by Real‐Time PCR in both vit C treated and vit C‐exo‐treated cells.Results: Vit C‐exo and vit C‐treated hLMSCs demonstrated slight reductions in TGFβ1 and TGFβ3 expressions compared to controls. In contrast, a modest increase in TGFβ1 and TGFβ3 levels was noted in hOA‐MSCs after vit‐C and vit C‐exo treatment. After vit C‐exo application, expression of miR155 and miR107 increased in hLMSCs and decreased in hOA‐MSCs. An opposite trend was observed with miR543 expression with an increase in hOA‐MSCs and a decrease in hLMSCs. miR29 associated with fibrosis was dramatically increased in hOA‐MSCs, but not in hLMSCs.Conclusions: In conclusion, we show that miRNA and RNA contents of treated mesenchymal stem cells may vary depending on the origin of tissue. These results suggest that vitamin C could promote a relatively more pronounced anti‐fibrotic character in hOA‐MSCs.The authors acknowledge the support from Eskisehir Osmangazi University, Scientific Research Projects (ESOGU‐BAP Grant ID: TOA‐2022‐2458).
A higher abundance of butyrate‐producing taxa in the gut is associated with lower glaucoma prevalence
Authors: Vergroesen Joëlle , Jarrar Zakariya , Weiss Stefan , Frost Fabian , Kraaij Robert , Medina‐Gomez Carolina , Amin Najaf , van Duijn Cornelia , Klaver Caroline , Jürgens Clemens , Hammond Chris , Ramdas Wishal 
Published: January 2024

Aims/Purpose: Glaucoma is an eye disease that is the commonest cause of irreversible blindness worldwide. It has been suggested that gut microbiota can produce reactive oxygen species and pro‐inflammatory cytokines that may travel from the gastric mucosa to distal sites, such as the optic nerve head or trabecular meshwork. There is evidence for a gut‐eye axis, as microbial dysbiosis has been associated with retinal diseases. Here, we investigated the association between glaucoma prevalence and the gut microbiome. Moreover, we analysed the association of the gut microbiome with intraocular pressure (IOP; risk factor of glaucoma) and vertical cup‐to‐disc ratio (VCDR; quantifying glaucoma severity).Methods: The discovery analyses included participants of the Rotterdam Study and the Erasmus Glaucoma Cohort. A total of 225 glaucoma patients were matched on age and sex with 1247 participants without glaucoma. Stool samples were collected and used to generate 16S rRNA gene profiles. We assessed associations with 233 taxa. We used data from the TwinsUK and the Study of Health in Pomerania (SHIP) to replicate our findings. The TwinsUK dataset consisted of 32 participants with glaucoma and 1542 unrelated, unmatched participants without glaucoma. The SHIP dataset consisted of a total of 2546 participants.Results: Several butyrate‐producing taxa (e.g., Butyrivibrio, Caproiciproducens, Clostridium sensu stricto 1, Coprococcus 1, Ruminococcaceae UCG 007, Shuttleworthia) were associated with lower glaucoma prevalence, lower IOP, and smaller VCDR. The replication analyses confirmed the findings from the discovery analyses.Conclusions: Large human studies exploring the link between the gut microbiome and glaucoma are lacking. Our results support the hypothesis that microbial dysbiosis plays a role in the pathophysiology of glaucoma. This research may support future research into the mediating role of butyrate‐producing taxa in the relation between dietary intake and glaucoma.
Neurodegeneration in diabetic retinopathy: An insight on its main signalling pathways
Authors: Gallego‐Martínez Alex , Andrés‐Blasco Irene , Casaroli Ricardo , Di Lauro Salvatore , Pinazo‐Duran Maria Dolores 
Published: January 2024

Aims/Purpose: In the latest years neurodegeneration has been considered as one of the main pathological processes involved in proliferative diabetic retinopathy's (PDR) onset and progression. We aimed to increase the understanding on the role of the main signalling molecules that participate in this phenomenon, including apoptotic, excitotoxic and neurotrophic factor pathways.Methods: Participants of both sexes were selected and programmed for vitrectomy by its diabetes mellitus 2 (DM2)‐derived vitreoretinal complications (PDR group, PDRG; n = 20), or by suffering macular hole, epiretinal membrane or rhegmatogenous retinal detachment (as the surrogate control group, SCG; n = 26). Vitreous body (VIT) and plasma (PLS) samples were collected and processed to determine the glutamate, caspase‐3 (CAS‐3) and brain‐derived neurotrophic factor (BDNF) levels. Next‐Generation Sequencing (NGS) techniques were applied to characterize the miRNA expression pattern in both groups.Results: Significantly higher VIT glutamate (p < 0.05) and CAS‐3 (p < 0.05), and significantly lower BDNF (p < 0.05) levels were detected in the PDRG. Significantly higher PLS glutamate (p < 0.05) and CAS‐3 (p < 0.05) levels were found in diabetics. However, PLS levels of BDNF showed no differences between groups (p = 0.80). NGS analysis showed a different miRNA expression pattern between both groups.Conclusions: Diabetes‐induced changes in retinal neurons/glia may be the key to discover preclinical biomarkers for better managing diabetic eyes. Glutamate, caspase‐3 and BDNF, playing important roles in the neurodegenerative processes occurring in PDR, are pivotal candidates to identify diabetics at high risk of sight‐threatening complications. Additionally, certain miRNAs could be playing an important role in these signalling pathways, being involved in PDR's neurodegenerative phenomenon.
Effect of obesity, dietary habits and physical exercise on visual acuity in healthy young subjects
Authors: Moreira‐Estebaranz Carolina , Remis‐Gonzalez Melisa , Gavilán Beatriz Sánchez , Hidalgo‐Saiz Beatriz , Giudice Luana , Cedrun‐Sanchez Juan , Puell María 
Published: January 2024

Aims/Purpose: To explore the effect of obesity, dietary habits, and physical exercise on high‐contrast visual acuity (HC‐VA) and low‐contrast visual acuity (LC‐VA) in healthy young subjects.Methods: A cross‐sectional pilot study was performed in 64 apparently healthy subjects (mean 21.6 ± 2.2 years of age; 24 men and 40 women). Best‐corrected distance HC‐VA and LC‐VA were measured using logMAR letter charts. Weight, height, and waist circumference (WC) were measured, and body mass index (BMI) and waist‐to‐height ratio (WHtR) calculated. A lifestyle questionnaire was used to investigate weekly physical activity (sedentary, active, and very active), the intake of fruits and vegetables per day (0–1 serving, 2–4 servings and 5 or more servings) and the consumption of saturated fat per day (0–1 serving and 2–4 servings). In addition, systolic (SBP) and diastolic blood pressure (DBP) were measured, and cardiovascular risk (CVR) was calculated using the Framingham calculator.Results: Mean CVR was normal (3.07 ± 2.2%) and spherical equivalent was −0.55 ± 0.88 dioptres. 7.8% of the subjects was underweight, 57.8% had normal weight (18.5 ≤ BMI < 25), 23.4% overweight (25 ≤ BMI < 30), and 10.9% obesity. Abdominal obesity was normal (WHtR < 0.5) in 76.5% and 23.4% had abdominal obesity (WHtR ≥ 0.5). WHtR and BMI were not significantly correlated with HC‐VA and LC‐VA. No significant differences were found in the means of HC‐AV and LC‐AV between the physical exercise groups and according to the daily intake of fruits and vegetables. In the group consuming higher servings of saturated fat, mean HC‐VA was 0.03 logMAR worse (p = 0.0474) and mean LC‐VA was 0.05 logMAR worse (p = 0.0068) than in the group that reported consuming lower servings of saturated fat.Conclusions: Obesity, physical exercise and fruit and vegetable consumption were not associated with HC‐VA and LC‐VA. Conversely, higher saturated fat intake was associated with worse HC‐VA and LC‐VA in young adults.
Retina hypoperfusion in multiple sclerosis: Is it only a consequence of atrophy?
Authors: Cerdà‐Ibáñez Marta , Manfreda‐Domínguez Laura , Duch‐Samper Antonio 
Published: January 2024

Aims/Purpose: To study if there are vascular changes in patients with multiple sclerosis (MS) when compared healthy controls, analysing oct and OCT‐angiography findings (choroidal thickness and retinal vascular density) at the macular level.Methods: The study compared two groups (controls and patients) and it analysed whether there were statistically significant differences in the different parameters studied using OCT: choroidal thickness and in the vascular macular plexuses, using OCT‐angiography. Any patient has an optic neuritis history. It was also studied whether there was a statistically significant correlation between anatomical parameters (radial nerve fibre layer, RNFL and ganglion cell layer, GCL) and vascular parameters matching cases and controls by age and sex.Results: We found a statistically significant reduction in macular choroidal thickness in patients when compared to controls. The study of retinal vascular plexuses showed that the superficial and deep retinal vascular plexuses and the choriocapillaris plexus showed significantly lower vascular density in the patients group. Variations in anatomical parameters between anatomical parameters and in vascular parameters between vascular parameters pairing cases and controls show direct correlations. Regarding the correlation between the differences in anatomical versus vascular parameters, we only observed a low direct correlation between the difference in the papillary RFNL and that of the superficial macular vascular plexus between case and control group.Conclusions: The density of macular vascular plexus and choroidal thickness proved to be significantly lower in MS patients than in healthy subjects. To date, it is not known to what extent hypoperfusion in MS is a cause or consequence of the brain disease or whether it is a simply association. Vascular parameters could be used as useful markers in the diagnosis and follow‐up of MS.
Anterior optic neuritis associated with clamydia trachomatis prostatitis
Authors: Nicolas Javier Garulo , Domínguez Laura Manfreda , Tepper Sergio Alfredo Maugard , Prades Gemma Ortega , Martínez Julia Pérez , Samper Antonio Duch 
Published: January 2024

Aims/Purpose: Parainfectious optic neuritis appears between one and 3 weeks after the onset of an infectious episode of viral or more rarely, bacterial aetiology. Hereby we present a case of bilateral optic disc edema presented during the course of a chlamydia trachomatis prostatitis, which spontaneously resolved after treatment.Methods: A 32‐year‐old patient who, in a context of a 10 days evolution prostatitis, suffers from a loss on the lower visual field in the right eye (OD) associated with cervical pain, fever and malaise. Ophthalmologic examination reveals bilateral optic disc oedema, and complementary tests show an elevation of C‐reactive protein up to 104 mg/L, visual evoked potentials with increased latency (more in OD) and the incidental finding of bilateral papillary drusen evidenced on computerized axial tomography.Results: The detection of chlamydia trachomatis DNA in a semen sample leads to an adjustment of antibiotic treatment. A month later, after fully healing of the prostatitis, the resolution of the papillary oedema in both eyes was observed with persistence of a pseudoedema typical of papillary drusen, as well as an improvement of the visual field whose residual affectation is reduced to arciform defects consistent too with the described drusen.Conclusions: This case has the peculiarity of presenting an optic disc oedema superimposed on a pseudoedema by papillary drusen. Although choroiditis has been described as a rare ophthalmic manifestation of systemic chlamydia trachomatis infection, there is no previous literature describing optic neuritis. In our patient, the proposed pathogenic mechanism is a parainfectious autoimmune reaction whose prognosis is excellent.References1. Chronic Ocular Chlamydia Trachomatis Infection in Rabbits. Boiko et al, 2014.2. Inflammatory Optic Neuritis. Ayuso et al, 2009.3. Optic Disc Drusen: a Systematic Review. Allegrini et al, 2020.
Papillophlebitis: A case series of a controversial diagnosis
Authors: Shamsher Ehtesham , Kawasaki Aki 
Published: January 2024

Aims/Purpose: Papillophlebitis refers to an isolated optic disc oedema with venous engorgement in asymptomatic patients as defined by Walsh and Hoyt in 1969. We report a case series of 3 patients who developed papillophlebitis related to SARS‐CoV‐2 vaccination, type 2 diabetes or idiopathic. A literature review was also performed.Methods: Observational case report of 3 patients and a review of the literature covering papillophlebitis cases was performed using Pubmed, Embase and Web of Science. Cases presenting with visual loss, RAPD, visual field defect or retinal vascular occlusion were excluded.Results: We report the case of 3 patients who did not have any visual complain and presented a unilateral optic disc oedema found by chance. The 1st patient was 33 year‐old and her past medical history was significant for SARS‐Cov‐2 vaccination. The 2nd patient was 6 year‐old and in general good health. The 3rd patient was known for a type 2 diabetes with no complications. For all patients, the visual acuity was 1.0, the intraocular pressure was normal, the anterior segment was quiet and the fundus showed a unilateral optic disc oedema without any haemorrhage. The RNFL OCT confirmed the presence of an optic disc oedema. The visual field was normal. An extensive blood test was negative for auto‐immune, inflammatory and vascular disease. In our patients, the optic disc oedema decreased spontaneously after a couple of months without any treatment and they retain 1.0 vision. A diagnosis of papillophlebitis was made. In the literature, the term papillophlebitis is not well‐defined and controversial. No treatment is required, and the condition resolved spontaneously over time. The visual prognosis is excellent as patients keep a 1.0 vision with a normal visual function. No recurrence has been reported.Conclusions: Papillophlebitis is diagnosed after ruling out any inflammatory, infectious or auto‐immune disease in asymptomatic patients who present a spontaneous recovery without any treatment as reported in our cases.
Breaking the mould: An essential need in optic neuritis management
Authors: Martí M. Ángeles Ruth Bort , Fustel Paula Boned , García Laura Fernández , Estruch Bonaventurs Casanova 
Published: January 2024

Aims/Purpose: To present a clinical case to highlight the importance of ophthalmological examination in the management of optic neuritis.Methods: Case report.Results: A 45‐year‐old woman with Sjögren's syndrome and a family history of MS presents to the emergency department. She complains of decreased vision OD for the past 4 days, with exacerbated‐by‐eye‐movements retroocular pain and migraine‐like headache. BCVA is amaurosis OD and 1 OI, with right RAPD and no colour vision impairment in OI. Except for optic disc oedema with splinter haemorrhages in OD the rest of the ophthalmological examination is normal. RNFL‐OCT reveals thickening in the OD (220 μm/110 μm). Brain CT and laboratory tests, including D‐dimers, are normal. A LP is performed to rule out infectious causes is normal. Neurofilament and ESR are also normal. Brain and spinal MRI show no abnormalities. Due to the severity, methylprednisolone therapy is initiated. One week later, her symptoms are stable, except for headache and retroocular pain improvement. Upon reassessment, despite preserved BCVA and Ishihara in OI, an increase in RNFL thickening is noted in OI (120 μm), with partial arcuate defect in visual field. Anti‐MOG, AQP4 and a panel of autoantibodies including anti‐Ro and anti‐La, are still pending. Considering the bilateral involvement, plasma exchange therapy is initiated. 14 days after, BCVA OU has improved to 1, and the visual field and Ishihara test have normalized. RNFL thickening is still observed OU (161/120 μm) and there is persistent optic disc edema OD. Anti‐MOG are positive, AQP4‐Ab are negative, and both negative in CSF.Conclusions: The coexistence of other autoimmune diseases, can lead to attributing the ON to that disease rather than considering the neuroinflammatory aetiology, leading to delayed diagnosis. The detection of subclinical bilateral involvement was crucial in escalating the therapeutic regimen. Seropositivity is the confirmatory diagnostic marker, but in many centres, it may be difficult to obtain reliable biomarker data.
A review of retinal analysis by OCT in murine models Alzheimer's disease
Authors: Sanchez‐Puebla Lidia , López‐Cuenca Inés , de Hoz Rosa , Ramirez Ana Isabel , Matamoros José A. , Lozano María Pilar Rojas , Salobrar‐Garcia Elena , Fernández‐Albarral José A. , Vázquez Alberto Arias , Salazar Juan Jose , Ramirez Jose Manuel 
Published: January 2024

Aims/Purpose: The use of murine models of Alzheimer's disease (AD) in the study of its pathophysiology is essential. In addition to a histological study of the retina, optical coherence tomography (OCT) allows a cost‐effective in vivo analysis of the retina. However, there is no standardization in the use of OCT in murine models of AD, leading to significant variations in study results. A review of the literature on murine models of AD analysed by OCT has been carried out. The characteristics of the animal model, the types of OCT, the retinal sectors analysed, the segmentation layers and the software used for segmentation were examined.Methods: We performed a literature search up to April 2023 using “MESH” terms in PubMed. The terms used were: “Alzheimer's mouse model”, “Optical Coherence Tomography”, “retinal optical coherence tomography” … as well as their combinations. We filter the articles by author criteria: the terms had to be in the title, in the abstract or in the article and they should be written in English or Spanish. Finally, 76 articles were used to the manuscript.Results: In comparison to studies using OCT in AD patients, only fourteen studies have utilized this technique to examine the retinas of murine AD models. Six different models, both first and second generation, were analysed, with most featuring presenilin mutations. There is no consensus regarding the measuring instrument, retinal area analysed, segmentation techniques, or software employed for analysis. Although some authors used the same OCT device, variations in other parameters hinder direct result comparison.Conclusions: It is essential to establish a unified criteria for OCT analysis of the retina in murine models of AD. This would allow the comparison of results and the establishment of measurement protocols. The use of OCT to understand the pathophysiology of AD would facilitate the longitudinal analysis of the disease and the possible identification of biomarkers.