bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergistic effect of mesenchymal stem cells and silver nanoparticles in the treatment of retinal degenerative diseases
Authors: Palacká Kateřina , Hermankova Barbora , Javorkova Eliska 
Published: January 2024

Aims/Purpose: Retinal degenerative diseases represent one of the leading causes of visual loss. Mesenchymal stem cells (MSCs) provide potential option for the treatment of several type of pathologies, including ocular diseases. Moreover, silver nanoparticles (AgNPs) are currently widely used in various fields of medicine mainly due to their antibacterial and antiangiogenic properties. Several studies showed their beneficial but also harmful effect. However, there are limited information about the synergistic effect of AgNPs with MSC‐based therapies.Methods: Chronical retinal degeneration was induced in BALB/c mice by repeated intraperitoneal application of sodium iodate (NaIO3). MSCs, AgNPs or MSCs plus AgNPs were intravitreally injected 48 h before the last application of NaIO3. Retinas were isolated after additional 7 days and tested by RT‐PCR for the expression of genes for rhodopsin (photoreceptors), Iba‐1 (microglia/macrophages), IL‐1β and galectin‐3. The presence of MSCs stained with PKH‐26 was analysed by flow cytometry.Results: It was shown that MSCs and MSCs applied with AgNPs were still present in the retina on day 7 after application. In all treated groups, the expression of the gene for galectin‐3 was decreased in contrast to untreated control. However, co‐application of MSCs with AgNPs had limited effect on downregulation of Iba‐1 and IL‐1β in contrast to MSCs or AgNPs treated group.Conclusions: The application of MSCs and AgNPs modulated immune response in chronical retinal degeneration but co‐application of MSCs with AgNPs decreased immunoregulatory effects comparted with single‐component therapy. Thus, there is a need for more investigation focusing on potential changes in MSCs applied with AgNPs.
Retinal microcirculatory parameters ‐ Clinical applications beyond ophthalmology
Authors: (Boy) Houben A. J. H. M. 
Published: January 2024

Microvascular dysfunction (MVD) is known as a classical complication of diseases like diabetes and hypertension. However, MVD is also known as a cause in the (early) development of cardiovascular and metabolic diseases. In addition, MVD has been shown to be associated with cardiovascular mortality.Measuring MVD in‐vivo is demanding, and, therefore, a broad application of these techniques in clinical studies has been lacking. One exception in this regard is analysing microvascular function in images of the retina. Many studies in various cohorts have consistently shown for instance that reduced retinal microvascular diameters are not only associated with current high blood pressure, but are also associated with as increased risk for developing hypertension in the future. Similar findings, changed diameters and risk prediction, have been found for diabetes.In the present lecture, an overview will be presented on the latest concepts and examples of retinal microvascular changes in structure and function in relation to cardiovascular and metabolic diseases.
Emerging therapies for geographic atrophy
Authors: Grzybowski Andrzej 
Published: January 2024

Geographic atrophy (GA) is a late‐stage form of age‐related macular degeneration (AMD) characterized by progressive degeneration of photoreceptors, retinal pigment epithelium (RPE), and choriocapillaris primarily in the macula. It was shown in AREDS studies that supplementation of high‐dose antioxidant vitamins (C, E, and beta‐carotene) and zinc, decrease the risk of progression to advanced AMD.It was suggested that the complement system, a part of the human immune system, plays an important role in the GA pathophysiology. Different complement genes have been linked to AMD in genome‐wide association studies, and the odds of GA were estimated to be 2.5 times higher per copy of a common risk allele (Y402H) of the CFH gene in individuals of European ancestry. In histologic studies complement proteins were found in drusen as well as elevated levels of complement proteins in the outer retinal tissue of postmortem eyes with AMD. Moreover, higher levels of activated complement products in plasma have been found in GA patients. Thus, several treatments targeting the complement system are investigated. The drugs that showed phase 3 efficacy and safety include pegcetacoplan and avacincaptad pegol, which are complement C3 and complement C5 inhibitors, respectively.
Inflammatory response of both retinas and superior colliculi to unilateral optic nerve axotomy
Authors: Galindo‐Romero Caridad , Cabrera‐Maqueda José María , Boia Raquel , Lucas‐Ruiz Fernando , González‐Riquelme María José , Ambrósio António Francisco , Santiago Ana Raquel , Vidal‐Sanz Manuel , Agudo‐Barriuso Marta 
Published: January 2024

Objective: Unilateral optic nerve crush (ONC) induces a bilateral inflammatory reaction affecting both injured and contralateral un‐injured retinas. However, few works have investigated the spread of inflammation along visual pathway. Our aim was to study the glial response and the underlying molecular changes in both retinas and the superior colliculi (SCi), the main projection areas of retinal ganglion cells in mice. In this species, >90% of RGCs project to the contralateral SC (cSCi).Methods: The left optic nerve of adult pigmented C57Bl/6 male mice were crushed (ONC) at 0.5 mm from the optic disk or underwent surgery without crushing (Sham). One group of intact mice was used as controls. Two studies were carried out:1) At 1, 3, 9 and 30 days post lesion (dpl) both retinas and SCi were freshly dissected and their RNA extracted. Using qPCR we measured the expression levels of TGF‐β1, IL‐1β, TNF‐α, Iba1, GFAP, MHC II and TSPO in retinas and SCi. In SCi extracts we also studied Casp3, CXCR1, Lcn2, IL‐6, CD206, IL‐4, and AQ4. Hptr and Gapdh were used as houskeepings. Intact retinas and SCi were used as controls.2) Three, 9 and 30 days after ONC or sham‐surgery immunodetection of microglia and macroglial cells was carried out in sagittal brain sections. The area occupied by GFAP and MHC II signal as well as the density of Iba1+ and CD68+ cells was quantified in both SCi. Intact brains were used as controls.Results: Sham surgery alone modified gene expression in both retinas and SCi compared to intact animals. Therefore, to isolate the effect of ONC, we compared ONC vs. Sham. After ONC, TNF‐α upregulated early in both retinas and IL‐β remained overexpressed in injured retina at day 30. GFAP overexpression was exclusively observed in injured retina while Iba1 overexpression was presented in both. TSPO and MHCII and Casp3 overexpression was observed only in the cSC.Anatomical microglial activation (rounded somas and CD68 expression) was observed in the cSC from day 3 onwards after ONC. In the ipsilateral SC (iSC) microglial cells did not show signs of activation. Astrocytes hypertrophied in both SCi from day 9 after ONC, but this response was also observed in Sham‐animals.Conclusions: Sham surgery promotes an inflammatory and glial response that must be considered in experimental designs. Unilateral ONC triggers a bilateral response which extends anterogradely and retrogradely along the visual pathway.
Nutraceutical supplementation in inherited retinal dystrophies
Authors: Velasco Sheyla , Olivares‐González Lorena , Morales Silvia , Valencia Daira , Esteban‐Medina Marina , Loucera Carlos , Salom David , García Emilio González , del Castillo Jose Miguel Soriano , Rodrigo Regina 
Published: January 2024

*Correspondence: rrodrigo@cipf.es; Tel: (+34 96 328 96 80)Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy causing progressive vision loss. Ocular redox status is altered in RP suggesting oxidative stress could contribute to their progression. In addition, it is accompanied by chronic and sustained inflammation, including M1 microglia activation. In our group we evaluated, both the effect of a mixture of nutraceuticals with antioxidant properties (NUT) and the effect of an essential fatty acid (EFA) supplement containing specialized pro‐resolving mediators (SPMs) on retinal degeneration in rd10 mice, a model of RP.Both compounds were orally administered to mice from postnatal day (P)9 to P18. At P18, the electrical activity of the retina was examined by electroretinography (ERG) and innate behaviour in response to light were measured. Retinal degeneration was studied via histology including the TUNEL assay and microglia immunolabelling. Microglia polarization (M1/M2) was assessed by flow cytometry, qPCR and histology. Redox status was analysed by measuring antioxidant enzymes and markers of oxidative damage.Interestingly, the NUT and EFA supplements ameliorated retinal dysfunction and degeneration by improving ERG recording and sensitivity to light, and reducing photoreceptor cell loss.The supplement reduced inflammation and microglia activation attenuating M1 markers as well as inducing a shift to the M2 phenotype in rd10 mouse retinas. These supplements also reduced oxidative stress markers of lipid peroxidation and carbonylation. These findings could open up new therapeutic opportunities with oral supplementation.
OCT biomarkers in wet type age related macular degeneration
Authors: Hassan Nihal 
Published: January 2024

OCT technology is evolving very quickly, and new retinal biomarkers are continuously described. Optical coherence tomography (OCT) is the most widely used technology for the diagnosis and follow‐up of AMD patients, which is widely used to study and guide the clinical approach, as well as to predict and evaluate treatment response.OCT biomarkers in wet type age related macular degeneration can be divided into two different categories.Biomarkers based on the retinal distribution of fluids and, structural biomarkers based on the presence or absence of specific features can be observed in the retinal layers, choroid, or vitreomacular interface.The aim of this review is to describe and analyse various structural OCT‐based biomarkers, which have practical value during both initial assessment and treatment follow‐up of wet type AMD patients.Central retinal thickness has been the most common and one of the first OCT identified biomarkers, today, other qualitative and quantitative biomarkers provide novel insight into disease activity and offer superior prognostic value and better guidance for tailored therapeutic management.The key importance of retinal fluid compartmentalization (intraretinal fluid, subretinal fluid, and subretinal pigment epithelium (RPE) fluid).In the second part, the structural alterations of different retinal layers in various stages of the disease (photoreceptors layer integrity, hyperreflective dots, outer retinal tubulations, subretinal hyperreflective material, and retinal pigment epithelial tears) will be analysed in detail.The last part of the review will focus on how alterations of the vitreoretinal interface (vitreomacular adhesion and traction) and of the choroid (sub‐RPE hyperreflective columns, pre‐choroidal clefts, choroidal caverns, choroidal thickness and choroidal volume, and choroidal vascular index) interact with AMD progression.This up‐to‐date review article provides a comprehensive description on how structural OCT‐based biomarkers provide a valuable tool to monitor the progression of the disease and the treatment response in AMD patients.
Does retinal microglia respond to peripheral nervous system injury?
Authors: Avilés‐Trigueros Marcelino 
Published: January 2024

The nervous system is the principal integration and coordination centre of the organism receiving, processing and transmitting information to produce a response that regulates and maintains homeostasis. In the central nervous system (CNS), homeostasis is regulated by haemato‐neuronal barriers that prevent free entry to immune system cells, although there is increasing evidence that neuro‐immunological interactions during injury, inflammation and chronic peripheral disease may contribute to the establishment and development of chronic neurodegenerative pathologies at the CNS level.Inflammation plays a significant role in the resolution and sequelae of CNS damage. In recent years, special attention has been dedicated to the role and phenotype of phagocytic cells acting in the CNS and, in particular, to the study of which macrophage subpopulations contribute to excessive or detrimental inflammation or, on the contrary, to beneficial repair or resolution of the lesion.All this raises the question of how local peripheral neuroimmunological interaction induces an inflammatory response in the CNS and how this can be better understood. The study of this phenomenon in the retina is of particular interest, as the retina does not receive neural afferents from other areas of the CNS.The use of experimental models of peripheral lesions of the peripheral nervous system, such as sciatic nerve trauma, or inflammatory lesions, such as the induction of a peripheral arthritic joint process, aims to investigate the time course of the response in the CNS to local peripheral inflammation in the retina of adult mice. The results reveal qualitative and quantitative cellular changes compatible with microglial activation processes in the retina, but no significant changes occur in its neuronal population. The presence and activation of haematic mononuclear‐phagocytic cells of myelopoietic origin are also observed in the retina, where they differentiate into microglia.In the absence of local retinal injury, we postulate that the detected neuroinflammatory reaction may be due to a preventive CNS defence reaction favouring neuroprotection since microglial cells derived from the haematic monocyte/macrophage cell population may consider within the M2 macrophage subtype, characterized by their ability to suppress proinflammatory immune responses and promote the expression of neuroprotective and repair genes.On the other hand, we must consider that activation of the mononuclear phagocytic system in the retina caused by a peripheral inflammatory process could potentially be detrimental to patients with neurodegenerative retinal diseases or contribute to their development.
Microglial changes in the retina and optic nerve of Parkinson's disease patients
Authors: Sáez Xavier Sánchez 
Published: January 2024

xsanchez@ua.esPatients that suffer from Parkinson disease (PD) also display non‐motor alterations. Among these non‐motor symptoms, there is clinical evidence of visual dysfunction in the pathology. Here, we will describe that there is retinal degeneration in these patients observed as a loss of retinal dopaminergic amacrine cells and intrinsically photosensitive retinal ganglion cells. Also, we describe in the ganglion cell layer the accumulation of phosphorylated alpha‐synuclein in axons and dendrites and the presence of Lewy bodies. Moreover, there is a degeneration of starburst amacrine cells, which are involved in motion direction selectivity. All these pathogenic processes are accompanied with an activation of microglia, which contribute to the retinal and optic nerve neurodegeneration providing a neuroinflammatory environment. By immunohistochemistry and bioinformatic analysis we have found that retinal and optic nerve microglia show morphological and protein expression profile changes in these patients. Taken together, these results demonstrate that in PD, microglia have a key role in the response to the retinal neurodegeneration.
Clinical validation of an adaptive optics visual simulator (VAO), a new instrument for the clinic
Authors: Hervella Lucía , Villegas Eloy A. , Robles Consuelo , Prieto Pedro M. , Artal Pablo 
Published: January 2024

Purpose: To validate in the clinic the Adaptive Optics Visual Simulator VAO (Voptica SL, Murcia, Spain).Setting: Laboratory of Clinical Optics, University of Murcia, Spain.Methods: Adaptive optics visual simulators have been widely used in research laboratories for various applications within the visual sciences, however, their use in clinical practice has been limited. Recently, an Adaptive Optics Visual Simulator (VAO, Voptica S.L) has been commercially introduced as a medical device for clinical use. VAO combines optical measurements and visual testing within the same compact instrument. It incorporates a Hartmann‐Shack wave‐front sensor to measure objective refraction and aberrations, together with a spatial light modulator capable of correcting or inducing any optical profile while performing visual testing. In seventy‐six eyes from 38 subjects, subjective refraction (SR) was measured using VAO and trial frame as a gold standard (GS). The agreement of spherical equivalent (M) and cross cylinders (J0 and J45) between SR with VAO and with the GS was estimated using different statistic parameters: 95% confidence limits (CL), Student's t‐test or Wilcoxon Rank Sum and Pearson correlation coefficient (r).Results: There was a strong correlation (r ranged between 0.88 and 0.99) for subjective refraction (M, J0, J45) between GS and VAO and there were not statistically significant differences (p > 0.05). The 95% CL of M, J0 and J45 were ±0.58, ±0.14 and ±0.14 D respectively. In addition to the subjective refraction, the visual acuity was also validated comparing BCVA values from GS with those from VAO, a high correlation (ρ = 0.73) was found for BCVA between both methods. Individual differences in BCVA between both methods were around or below 1 line since 95% CI was ±0.10 LogMAR.Conclusions: Our findings suggest that VAO, the new instrument for vision analysis based on adaptive optics, provides measurements that are comparable to those of the gold standard technique in healthy eyes with 73.7% of the spherical equivalent (M) differences between them within ±0.25 D and 68.4% for BCVA within ±0.05 LogMAR. Thus, subjective refraction found with VAO can be used for prescribing, as a baseline to simulate any optical profile and to customize the selection of the ablation and the IOL design in refractive surgery.
Remote assessment of visual acuity during video consultations
Authors: Galindo‐Romero Caridad , López‐López José A. , Meroño‐Gutiérrez Marta , Bryce Elle , Edwards Lydia , Hagerty Eilidh , McDonald Kirsty , García‐Ayuso Diego , Di Pierdomenico Johnny , Cameron Lorraine , Wallace Claudine , Valiente‐Soriano Francisco J. 
Published: January 2024

Purpose: To assess the reliability and repeatability of visual acuity (VA) measurement obtained remotely via electronic devices using the Optonet Vision Unit (OVU), a web‐based digital eye care software used in eye care practitioner's consultations.Methods: A total of 78 adult participants (20–54 years of age) were recruited, 36 from Glasgow Caledonian University (Scotland, UK) and 42 from the University of Murcia (Spain). Each participant underwent a monocular VA test and retest (TRT, right eye) using three different VA charts, two of them performed in the practitioner's consultation: the Early Treatment Diabetic Retinopathy Study (ETDRS) chart as the gold‐standard VA test and the OVU computerized VA chart (Optonet Ltd©, UK) designed according to the ETDRS format; and one remote VA measurement obtained in another room using OVU. Prior to the remote VA measurement, each participant set up the video‐consultation version of the OVU software on a screen through directions provided by the examiner from another room via a Zoom call (Zoom Video Communications©, Inc., CA, USA). Small adjustments could be made by the examiner using the information that the electronic device used by the participant transmitted to the online software to which it was connected. Participants were asked to stand about 4 meters from the screen and instructed to read the letters presented. The order of VA acquisition was randomized for each participant. VA scores were recorded in logMAR, and data were analysed with SPSS. The duration of the video consultation was timed from the moment the Zoom call link was sent to the participant until the VA measurement was completed.Results: The mean ± standard deviation (SD) of VA measured was −0.006 ± 0.14 logMAR with the ETDRS chart, −0.07 ± 0.15 logMAR with OVU and –0.05 ± 0.16 logMAR with remote OVU. TRT variability (range comprising 95% differences) showed a good agreement in ETDRS chart (mean difference ± 0.0077 logMAR, 95% CI: −0.014 to 0.06); OVU (mean difference ± 0.0028 logMAR, 95% CI: −0.012 to 0.10); and remote OVU (mean difference ± 0.0024 logMAR, 95% CI: −0.012 to 0.08). The duration of the remote VA assessment was 6.68 ± 2.21 min.Conclusion: This study demonstrates the potential of OVU charts for clinical and teleconsultation uses, which may be useful for VA measurement in remotely based patients.
New technologies for eye care practitioners
Authors: Martín‐González Santiago , Portela‐Camino Juan A. 
Published: January 2024

Keywords: orthoptics, optometry, visual rehabilitation, visual therapy.In the 1920s, Mary Maddox opened a vision rehabilitation center in London, being considered the first orthoptist (an unknown profession in Spain, whose competences fall on Optics‐Optometry). Her father, Ernest E. Maddox, an ophthalmologist, had developed various instruments to investigate binocular vision. The new discipline seeks to improve the binocular state of the patient, affected by symptomatic tropias or phorias, through exercises that train eye movements, ductions, versions, vergences, fixations and saccades. Amblyopia, on the other hand, is still treated by occlusion of the fellow eye, following practices that began in the 18th century (George L. de Buffon).During the 20th century, orthoptic specialists used different instruments, which have survived to this day, for the diagnosis and treatment of deviations. Perhaps the most advanced of them is the synoptophore, capable of determining objective and subjective deviations, the presence of normal or abnormal correspondences, and the presence of suppression scotoma. The synoptophore is also used in rehabilitation, together with the aperture rule, vectograms or the Brock string. However, in the case of tropias and during the 20th century, orthoptic therapy occupies a very marginal place compared to the surgical solution. The Hubel and Wiesel experiments in the 60s and 70s were interpreted restrictively, rooting concepts such as the so‐called critical period, which discouraged any attempt to treat amblyopia beyond occlusion, particularly in adulthood.However, research carried out from the second half of the 20th century to nowadays provides evidence of the usefulness of vision rehabilitation in the treatment of strabismus and non‐strabismus visual dysfunctions, and in the recovery of amblyopia in adulthood. Basic research led by Dennis M. Levi of the University of California at Berkeley and Robert F. Hess of McGill University, as well as clinical research by the Paediatric Eye Disease Investigator Group, PEDIG, are good examples.New technologies based on computers are currently renewing and revitalizing orthoptic practice, both in diagnosis and treatment. Eye‐trackers combined or not with Virtual Reality allow (a) to record eye movements accurately and objectively, and to identify visual behaviour and deficits, and (b) to train those movements, providing positive feedback to the patient. Screens have evolved from conventional models, later 3D and finally Virtual Reality, allowing dynamic exercises and avoiding other limitations, such as postural ones. Software algorithms adapt the difficulty of the exercises to patient's performance, record therapy compliance, and store the results in the cloud for remote control of home therapy. In addition, gamification techniques allow increasing the patient's motivation and adherence to treatment. These improvements are essential in perceptual learning, the paradigm of the new visual rehabilitation model.