bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased secretory autophagy in retinal pigment epithelial cells of the 5xFAD mice
Authors: Ruuth Johanna , Tamminen Toni , Toropainen Elisa , Koskela Ali , Tanila Heikki , Kaarniranta Kai 
Published: January 2024

Purpose: Disturbed proteostasis and oxidative stress have a key role in Alzheimer's disease and age‐related macular degeneration pathology. Constant oxidative stress and disturbed proteostasis lead to intracellular protein aggregation and possibly the activation of secretory autophagy. In this study we assessed the oxidative stress and secretory autophagy related biomarker changes in the retinal pigment epithelium (RPE) of the 5xFAD mice model expressing abundant levels of the human beta‐amyloid.Methods: The eyes of 3‐, 6‐ and 12‐month‐old WT (n = 5) and 5xFAD (n = 5) mice were enucleated, paraffin fixed and examined by immunomicroscopy. The paraffin sections were immunostained for beta‐amyloid and the key secretory autophagy markers Sec22b, TRIM16, galectin 8, IL‐1β, HMGB1 and ferritin. Moreover, the sections were stained for oxidative stress marker 4‐HNE and antioxidant enzyme catalase. Protein degradation related markers ubiquitin (Ub) and SQSTM1/p62 were analysed from 6‐ and 12‐months timepoints.Results: Immunohistochemistry analysis revealed that the oxidative stress and protein degradation related markers were upregulated in the RPE of 6 and 12‐months old 5xFAD mice suggesting presence of oxidative stress and protein aggregation. TRIM16 and galectin 8 were increased in the RPE of the 6‐ and 12‐months old 5xFAD mice, while the increased expression of Sec22b was observed in 3‐ and 6‐months timepoint. IL‐1β, HMGB1 and ferritin were accumulated at the basal side of the RPE cells/Bruch's membrane in 6‐months old 5xFAD mice. The high accumulation of beta‐amyloid was detected in drusen like structures. Electrophysiological analysis revealed decreased scotopic and photopic signalling compared to WT mice.Conclusions: 5xFAD mouse model seems to be a good model to study protein aggregation and activation of the secretory autophagy in response to degenerative retina processes.
Menopause‐induced neurodegeneration of retinal ganglion cells in a model of an acute retinal ischemia in rats
Authors: Rodak Piotr , Olakowska Edyta , Pacwa Anna , Machowicz Joanna , Smedowski Adrian 
Published: January 2024

Aims/Purpose: To assess the influence of surgical menopause on the function and survival of retinal ganglion cells in a rat model of optic nerve crush.Methods: A total of 27 rats, aged 8 weeks, were divided into two groups based on the duration between ovariectomy (OVE) and euthanasia. Subgroups consisted of OVE, OVE combined with optic nerve crush (ONC), and ONC alone. All surgical procedures were conducted under general anaesthesia. Menopause was induced through OVE, which involved the surgical removal of ovaries. ONC was performed to induce acute retinal ischemia. Retinal function was evaluated using electroretinography (ERG). Retinas were stained for β3‐tubulin, NeuN, Erα, Erβ, and Iba1. Cell loss ratios were assessed through manual counting using ImageJ software.Results: After a two‐week menopause period, a reduction in retinal interneurons (RI) density was observed, but no significant decline was observed in retinal ganglion cell (RGC) count. The counts for NeuN were 373 ± 58 and 317 ± 55 (healthy vs. OVE, p < 0.02), and for β3‐tubulin were 197 ± 42 and 212 ± 38 (healthy vs. OVE, p > 0.05), respectively. Seven weeks after OVE, menopause affected RI but not RGC, with counts of 404 ± 49 and 378 ± 61 (healthy vs. OVE, p < 0.05), and 286 ± 32 and 287 ± 51 (healthy vs. OVE, p > 0.05) for NeuN and β3‐tubulin, respectively. Following the ONC procedure, the NeuN cell count was 345 ± 28 and 286 ± 40 (ONC and ONC + OVE, respectively, p < 0.0001), and for β3‐tubulin it was 221 ± 28 and 200 ± 37 (ONC and ONC + OVE, respectively, p < 0.05). In the preliminary analysis of ERG, a significant decrease in PhNR amplitudes was observed in the OVE group, while PhNR was severely diminished in the OVE + ONC group.Conclusions: Deprivation of estrogens through surgical menopause leads to accelerated retinal neurodegeneration, primarily affecting retinal interneurons. The absence of estrogens increases the vulnerability of RGCs to insults, resulting in expedited RGC loss during acute retinal ischemia.
Mitophagy‐reporter Muller cell line (MQ‐MG2) as a novel platform for ocular drug discovery
Authors: Anderson Aidan , Bouzinab Kaouthar , Rudzinska Paula , Ganley Ian , Wallace Graham , Romero Jose M. 
Published: January 2024

Aims/Purpose: The controlled activation of mitophagy has emerged as an exciting therapeutic angle in the treatment of ocular conditions, including diabetic retinopathy and age‐related macular degeneration. Here, we report a novel Muller cell line (MQ‐MG2) for the rapid screening of mitophagy‐activating drugs.Methods: MQ‐MG2 were cloned from spontaneously immortalized primary Muller cells (PMCs) derived from mitophagy reporter (Mito‐QC) mice. Muller glia characteristics were assessed by immunocytochemistry, western blotting, and metabolic flux (Seahorse). The versatility of MQ‐MG2 to detect mitophagy‐activating drugs was tested via pharmacological activation (PINK1‐dependent and PINK1‐independent) and further validated in vivo using Mito‐QC mice.Results: MQ‐MG2 were expanded over 50 passages while retaining expression of Mito‐QC reporter. MQ‐MG2 showed key phenotypic markers of Muller glia, including glutamine synthetase, glial fibrillary acidic protein, Aquaporin 4, and Interleukin‐33. At the bioenergetic level, MQ‐MG2 showed lower basal‐ and ATP‐linked respiration than PMCs, while displaying superior reserve capacity (p < 0.001). Indicative of equivalent glycolytic profiles, extracellular acidification rates (baseline and stressed) remained comparable to PMCs. Importantly, MQ‐MG2 showed excellent sensitivity to screen for mitophagy‐activating drugs, including novel small‐molecules acting through (putative) PINK1‐independent pathways. The versatility of MQ‐MG2 as a drug discovery platform was validated in vivo, where oral administration of PINK1‐independent activator (PIA‐01) amplified mitophagy at the outer retina dose‐dependently.Conclusions: MQ‐MG2 enables rapid and reliable detection of mitophagy‐activating drugs for ocular application. This platform overcomes the limitations of primary cultures, including variability due to cellular senescence and heterogeneity, while minimizing the need for animals in drug discovery.
Drusen of the retinal pigment epithelium of the parapapillary region
Authors: Jonas Rahul , Jonas Jost , Panda‐Jonas Songhomitra , Jonas Shefali 
Published: January 2024

Aims/Purpose: The description of the morphology, the occurrence and the associations of parapapillary drusen of the retinal pigment epithelium (dotRPE).Methods: A histomorphometric analysis of enucleated human eyes using a light microscope.Results: 83 enucleated human eyes (mean axial length 25.9 ± 3.2 mm; range 20.0–35.0 mm) were included for analysis using light microscope. The eyes with parapapillary dotRPE (29 of 83 eyes, 35%) in comparison with the other eyes had a shorter axial length with 24.0 ± 1.8 mm vs 27.0 ± 3.3 mm (p < 0 0.001). Additionally, a higher occurrence (27 of 29 vs 12 of 54 eyes, p < 0.001) and greater girth (213 ± 125 μm vs 96 ± 282 μm, p < 0.0001) of the parapapillary alpha zone. Bruch's membrane (BM) was thicker in the parapapillary beta zone (8.4 ± 2.7 μm vs 3.9 ± 2.0 μm, p < 0.001) and in the parapapillary alpha zone (6.6 ± 3.9 μm vs 4.4 ± 1.5 μm, p = 0.02). Underneath the dotRPE and in the parapapillary alpha zone the choriocapillaris appeared open, while it appeared intact in the center of the parapapillary beta zone. Although BM was thicker (p = 0.001) in alpha zone compared to beta zone, it was thicker in beta zone compared to region outside of either alpha or beta zone (p < 0.001). The thickness of BM outside of the parapapillary zone of alpha or beta was not correlated with either the occurrence of dotRPE (p = 0.47) or the axial length (p = 0.31). A basal membrane stained positive for PAS connected the RPE cells of the parapapillary dotRPE. The cell density of the RPE increased in the alpha zone compared to bordering regions (22.7 ± 7.3 cells/240 μm vs 18.3 ± 4.1 cells/240 μm, p < 0.001). Parapapillary dotRPE occurred in 69% (27 of 39) of eyes with a parapapillary alpha zone.Conclusions:: Parapapillary dotRPE as fibrous pseudo‐metaplasia correlated with a shorter axial length, thicker BM in the alpha and the beta zone, as well as a higher prevalence and larger size of the alpha zone. This may be helpful to set apart the glaucomatous parapapillary beta zone and the myopic beta zone.
A microbial infection‐resistant 3D bioprinted material for corneal stroma regeneration
Authors: Lemonche Gerard Boix , Niemi Essi M. , Muñoz Georgina Faura , Scholz Hanne , Skerlavaj Barbara , Petrovski Goran 
Published: January 2024

Aims/Purpose: To assess whether 3D bioprinted, scaffold‐immobilized antimicrobial peptides (AMPs) derivatives, BMAP27(1–18) and hLF(1–11) can inhibit microbial colonization to obtain infection‐resistant 3D bioprinted hemi‐corneas.Methods: The research followed the tenets of the Declaration of Helsinki. 3D bioprinting was used to produce transparent nanocellulose‐ and alginate‐based 3D constructs. Functionalized 3D bioprinted scaffolds with AMPs were characterized by contact angle and transparency measurements. The antimicrobial and antifungal activity of the peptides in solution were investigated by minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) methods against Staphylococcus epidermidis ATCC 35984, S. aureus ATCC 25923, S. epidermidis ATCC 12228, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922 and Candida albicans ATCC 90028. The antimicrobial activity of the AMP‐modified scaffolds was studied against P. aeruginosa and C. albicans reference strains by colony forming unit (CFU) counts, and their biocompatibility was investigated by measuring the viability of primary human/cadaver‐isolated corneal stromal‐mesenchymal stromal cells (CS‐MSCs).Results: The original and modified peptides showed MIC (MBC) values of 1–4 (2–8) μM and 16 – >128 (32 – >128) μM, respectively, against S. epidermidis ATCC 35984, S. aureus, S. epidermidis ATCC 12228, P. aeruginosa, E. coli and C. albicans, while ncBP‐BMAP27(1–18) and ncBP‐hLF(1–11) values were 1–16 (2–32) μM 4–128 (4 – >128) μM, respectively, against all the pathogens. The modified scaffolds containing the AMPs attached to the scaffolds, demonstrated the ability to kill 20–96% of P. aeruginosa, and between 60–70% of C. albicans. All the 3D bioprinted scaffolds showed no cytotoxicity towards CS‐MSCs.Conclusions: We could successfully combine 3D bioprinting with immobilization of AMPs that show promising antimicrobial activity against two of the most dangerous pathogens to the cornea, while a good cytocompatibility for the CS‐MSCs could be achieved. Optimal bioink composition and cellularization of tissue equivalents are essential in fine‐tuning a method to promote the current 3D bioprinting technique as a future treatment modality for corneal regeneration.
Structurally enhanced perimetric examination
Authors: Evans Josephine , Crabb David , Ometto Giovanni , Montesano Giovanni 
Published: January 2024

Aims/Purpose: To assess the use of structural data to guide perimetric examination.Methods: Two perimetric strategies were tested on ten healthy participants: standard ZEST with population‐based prior distributions and Structural‐ZEST (S‐ZEST), enhanced with OCT data to determine the starting parameters. Both strategies were tested twice, in random order. The Compass Automated Perimeter (CMP, iCare) was used to collect the perimetric data through the Open Perimetry Interface and bespoke Shiny user interface (UI). The UI was used to import the Spectralis SD‐OCT scans (Heidelberg Engineering, Germany) and align the OCT data with the fundus image captured by the CMP. A 10–2 grid was centred on the fovea of each participant, aligned with the fovea‐disc axis. The UI calculated the Ganglion Cell Layer (GCL) thickness corresponding to each test location, after accounting for ganglion cell displacement. The starting priors for S‐ZEST were modelled using an independent dataset of glaucoma and healthy subjects. Bland–Altman plots were used to quantify test–retest variability. Bootstrap was used to calculate confidence intervals (CIs) and p‐values to compare the widths of the 95%‐Limits of Repeatability (LoR). Correlation between GCL thickness and sensitivity (dB) and the difference in test duration was calculated using linear mixed effect models. Agreement was quantified with the mean difference between the results of the two strategies.Results: 95%‐LoRs for S‐ZEST of the two devices were similar (p = 0.829). The structure–function correlation was significant for both (p < 0.001), and very similar between S‐ZEST (R2 = 0.24) and ZEST (R2 = 0.23). There was a small but statistically significant mean difference in sensitivity between S‐ZEST and ZEST (0.56 [0.35, 0.77] dB, p = 0.034). S‐ZEST was 2.7 [1.2, 3.5] min faster than ZEST (p < 0.001).Conclusions: S‐ZEST significantly shortened testing time without reducing repeatability in healthy observers.
Peripheral refraction and retinal activity with dual focus contact lenses for myopia control
Authors: Fernandes Paulo , Amorim‐de‐Sousa Ana , Queirós António , González‐Meijome José Manuel 
Published: January 2024

Aims/Purpose: Contact lenses (CLs) for myopia control have shown optimistic eye growth retention in children but, the retinal mechanisms of defocus still unclear. This work evaluated the retinal response and peripheral refraction with a soft CL for myopia management in myopic eyes.Methods: The visual acuity (VA), peripheral refraction and the retinal electrical activity were obtained from sixteen myopic (between −0.75 D and − 6.00 D, astigmatism >1.00 D) subjects (27.5 ± 5.7 years, 12 female), with two material‐matched CLs (Omafilcon A): a single‐vision CL (SV) and a myopia management dual‐focus CL (DF). Peripheral refraction was assessed with an open‐field autorefractometer (WAM‐5500, GrandSeiko Co. Lt) in four meridians separated by 45° at 2.50 meters distance. The global‐flash multifocal electroretinogram (gf‐mfERG) was recorded with the Reti‐port/scan21 (Roland Consult) using a stimulus of 61‐hexagons. The implicit time and response density (in nV/deg2) of the direct (DC) and induced (IC) components were analysed. Only the data of a single eye per subject was randomly used for analysis.Results: The two CLs designs showed similar VA (p > 0.050). The DF induced a myopic shift of the SV peripheral refraction in most retinal eccentricities (p < 0.050). There were no differences in the implicit times of the retinal response between CLs designs. The DF increased the response density of both DC and IC components at all retinal areas, with a statistically significant difference in the parafoveal DC component (median difference of 2.77 [6.23–1.44] nV/deg2, p = 0.038).Conclusions: The results showed that the retina responds differently to a SV and a DF CLs. The myopia management CL increased the electrophysiological response of the retina without affecting the time domain of the response. Besides other mechanisms potentially involved, the foveal and parafoveal retinal activities might be involved in the mechanism of myopia control with these lenses.
The aged mouse retina: Anatomical and functional study of retinal ganglion cells
Authors: Ramírez Kristy Tatiana Rodríguez , Muñoz María Norte , Ortega Alejandro Gallego , Vidal‐Sanz Manuel , Agudo‐Barriuso Marta 
Published: January 2024

Aims/Purpose: the purpose of this work is to analyse anatomically and functionally the population of retinal ganglion cells (RGCs) throughout the mouse lifespan.Methods: Retinal functionality was studied by electroretinogram in male and female C57BL/6J mice at 3, 6 and 18 months of age. Retinas were dissected as flat mounts at 3 and 18 months, the total number of RGCs immunodetected with Brn3a and automatically quantified.Results: Regarding retinal functionality, we observed that the pSTR wave significantly decreased in males at 6 months (p < 0.01 vs. 3 months) and progressed significantly at 18 months (p < 0.01 vs. 6 months). In females, RGC functional decline was observed later than in males, at 18 months (p < 0.001 vs. 3 months). The loss of RGC functionality was not accompanied by RGC death, as the total number of RGCs remained constant in both sexes from 3 to 18 months of age.Conclusions: Aging of the retina is associated with functional changes that may be due to neuronal dysfunction rather than cell loss.
Comparison of changes in ocular aberrations with accommodation and accommodative facility
Authors: García Maria Mechó , Carbonell María Arcas , Hospital Elvira Orduna , Cano Ana Sánchez 
Published: January 2024

Aims/Purpose: This study aimed to analyse whether a relationship exists between subjectively measured monocular Accommodative Facility (AF), the magnitude of the revolution‐symmetric Zernike coefficients C20, C40 and C60, and the objectively measured Accommodative Response (AR).Methods: A total of 66 eyes, from 33 healthy young volunteers (26 women and 10 men) with a mean age of 25.12 ± 3.40 years (range age 20–30) participated in this study. Three measurements were made for each eye with the aberrometer Hartmann‐Shack (IRX3, Imagine Eyes, Orsay, France). The stimulus vergence was increased from 0 to 5 D (near vision) in steps of 0.5 D. The AR for each Zernike coefficient was calculated as the difference between the value at 5 D and the value at 0 D, for 4.0 mm pupil size. Monocular assessment of AF was assessed monocularly and conducted at 40 cm ± 2.00 D flippers. Statistical analysis was performed to determine a relationship between the Zernike coefficients, AR and AF. The coefficient of determination (R‐squared) was calculated to measure the proportional amount of variance.Results: The results showed that the highest values of R‐squared were obtained for the C20 coefficient measured at 5D of accommodation (R2 = 0.196, p < 0.01). Lower values were obtained for C40 and C60. The R‐squared values decreased from 0D (R2 = 0.097, p = 0.10) to 5D (R2 = 0.044, p = 0.60) for C40. However, there was an increase in R‐squared values from 0D (R2 = 0.0081, p = 0.47) to 5D (R2 = 0.058, p = 0.05) for C60.Conclusions: No clear trends were found when comparing the Zernike coefficients C20, C40 and C60, analysed in three stages of accommodative demand compared with the accommodative facility measured.The Zernikes coefficients analysed do not explain the differences in AF in this sample of young adult healthy eyes. However, there was found a trend that deserves further investigation.
Eyecare staff knowledge in three Belgium nursing homes
Authors: Moghaddam Zahra Javdani Sanatgar , Goes Frank 
Published: January 2024

Aims/Purpose: Vision loss in elderly people may affect physical and mental health and speed up cognitive decline. Identifying visual dysfunction and staff education may improve ophthalmic care in nursing homes, but it is not yet known which practices have been implemented in Belgium.Methods: Prospective cross‐sectional survey performed in Belgium between December 2022 and January 2023, by email and hardcopy. Survey questions were based on the literature, were focused on monitoring practices, staff knowledge, and other aspects shown to affect residents' vision care. Descriptive statistics and Chi‐Square analysis were used for data analysis.Results: A total of 46 staff members (31 women, 15 men) of three Belgium nursing home staff were interviewed. The questionnaire revealed that there was not enough access to screening tools to identify vision impairments.Conclusions: Access to monitoring procedures or screening tools are not commonly available staff education in Belgium nursing homes may be insufficient.Keywords: Staff education, staff knowledge, nursing home, ophthalmic screening.
Relationships between regional retinal sensitivities assessed by microperimetry and their corresponding retinal layer thicknesses in healthy middle‐aged subjects
Authors: Puell María , Remis‐Gonzalez Melisa , Moreira‐Estebaranz Carolina , Cedrun‐Sanchez Juan 
Published: January 2024

Aims/Purpose: To investigate relationships between regional differential light sensitivity (DLS) and inner and outer retinal layer (IRL and ORL) thicknesses in healthy middle‐aged adults.Methods: Measurements were made in 42 eyes of 42 healthy individuals of mean age 51.3 ± 5.4 years (range 40–59 years), spherical equivalent (SE) between ±3.50 D and good visual acuity. Mesopic fundus‐controlled perimetry was used to measure regional DLS. Spectral‐domain optical coherence tomography (SD‐OCT) was used to measure IRL (ganglion cell‐related layer) and ORL thicknesses. DLS and retinal thickness measurements were recorded for five subfields: central fovea (1 mm diameter) and the quadrants temporal, nasal, superior, and inferior of a parafoveal ring of outer diameter 3 mm and inner diameter 1 mm. Relationships between regional DLS and corresponding IRL and ORL thicknesses were assessed through univariate and multivariate analysis.Results: Mean DLS measured in the inferior parafoveal ring quadrant was significantly correlated with mean IRL thickness (rho = −0.50; p = 0.0045). This correlation was negative, meaning that a thicker IRL was related to a worse DLS. No significant correlations emerged between mean DLS and corresponding ORL or IRL thicknesses for the other subfields. Subsequent forward stepwise multiple linear regression analysis to correct for potential confounding factors revealed that IRL thickness and SE emerged as significant predictors of DLS in the inferior quadrant (R2 model = 33%; p = 0.0004).Conclusions: A thicker macular IRL, possibly indicating transient gliosis, was associated with a worse DLS in healthy middle‐aged eyes.