bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contribution of intraocular pressure‐dependent and pressure‐independent glaucoma models to neuroprotection
Authors: Aviles‐Trigueros Marcelino 
Published: December 2022

AbstractGlaucoma is considered a heterogeneous group of degenerative optic neuropathies characterized mainly by an ongoing loss of retinal ganglion cells (RGCs) which causes progressive deterioration of the visual field and irreversible blindness. The aetiology and pathophysiology of glaucoma are not known in detail and are a matter of debate. Although the most significant risk factor in the development and progression of glaucoma correlates with elevated intraocular pressure (IOP), at present the only treatment available to prevent or delay its development is to reduce IOP by medication or surgery to slow its detrimental effects. But reducing IOP alone does not stop the progression of the disease. Therefore, IOP may not be the only motive for glaucomatous retinopathy and optic neuropathy, and there could be other hidden mechanisms contributing to the loss of RGCs.A suitable animal model of neurodegenerative disease, such as glaucoma, should be easy to induce and reproduce, feasible and predictable, and allow detection and quantification at the biochemical, morphological and functional levels of the induced pathological changes. However, no model emulates all aspects of a pathology such as glaucoma, which is likely to have more than one aetiology and manifest itself through different pathological mechanisms. Hence, the interest and need to establish and use different experimental models in rodents to improve our understanding of the pathophysiology of glaucoma and to investigate possible neuroprotective agents. In general, experimental models of glaucoma established in rodents involve a transient or chronic increase in IOP above normal values, which allows us to study the pathological changes associated with ocular hypertension. However, elevated IOP may not be the only cause of glaucomatous retinopathy and optic neuropathy, hence the need for models that do not involve an increase in intraocular pressure to deal with specific issues of the evolution of this pathology, such as optic nerve injury, retinal ischaemia/reperfusion, intravitreal injection of excitatory amino acids or endothelin‐induced optic neuropathy.Results obtained in different experimental models of glaucoma mimicking ocular hypertension or optic nerve damage have confirmed the existence of morphofunctional differences in the time course of RGC loss, both between different types of RGCs and between different lesions. As well as the effects on other retinal cell populations. In this regard, in the outer retina, there is a significant contrast between damage caused by ocular hypertension and optic nerve injury. Both axotomy and ocular hypertension induce a selective loss of RGCs, but ocular hypertension also promotes a loss of photoreceptors.Thanks to the different glaucoma models studied, the findings obtained have contributed to improving our knowledge of glaucomatous pathology and to the development of future neuroprotective therapies.
I‐VISION project. A new step in artificial vision
Authors: Garrido Jose Antonio 
Published: December 2022

AbstractThe i‐VISION project aims to develop next‐generation of retinal prosthesis technology in efforts to restore high‐acuity artificial vision to individuals blinded by retinal degeneration. Retinal prostheses operate by electrically stimulating retinal neurons that survive the degeneration in a spatiotemporal pattern that is interpreted by the brain as vision. Presently, the challenge to implement thousands of small‐diameter electrodes and increasingly more sophisticated stimulation protocols that can adapt to the patients' needs has not been met, which severely limits the quality of restored vision in current retinal prostheses.In this presentation I will present how i‐VISION is set to address some of the challenges hindering the performance of current retinal prostheses, with a focus on the use of revolutionary miniaturized electrode nanotechnology based on graphene. Graphene microelectrodes are capable of mediating high‐charge injection highly localized that will improve the spatial resolution at the neural interface, and locally monitoring the stimulation efficacy, allowing a future adaptive therapy strategy. In addition, I will present work of the i‐VISION consortium on the use of advanced in vitro and in vivo imaging techniques of the evoked retinal and cortical responses to quantify the area of neurons activated by the electrical stimulation, with the ultimate goal of generating maps of retina‐visual cortex interconnectivity.
New trends in retinal imaging
Authors: Cordeiro Francesca 
Published: December 2022

AbstractLatest advances in ophthalmic imaging includes their recognition as biomarkers. Biomarkers are increasingly used in medicine as indicators of a disease and treatment response. The eye lends itself to providing different biomarkers as structural indicators of pathology. In addition to uses of OCT, new and emerging technologies including OCTA, AO, multispectral imaging, polarizarition techniques, fluorescent imaging including FLIO, curcumin and DARC will be discussed, as will their applications to glaucoma, retinal and neurodegenerative conditions.
From mouse to primate: Retinal circuit disassembly and plasticity in glaucoma
Authors: Ou Yvonne 
Published: December 2022

AbstractPrecise connections between synaptic partners are shaped during development to ensure proper neural circuit function, but how these connections are disassembled and rearranged after injury is less well understood. In glaucoma, the ganglion cell is injured but very little is known about how the presynaptic circuitry is perturbed. Furthermore, the ability to diagnose and treat glaucoma at an optimal stage before irreversible retinal ganglion cell loss occurs requires a comprehensive understanding of inner retina circuit disassembly and plasticity. Recent studies in rodent, including our work, suggest that specific ganglion cell types are more vulnerable to glaucomatous injury. In this talk I will discuss the specificity and timing of anatomic retinal circuit disassembly in mouse and primate experimental glaucoma and the potential for the adult diseased retina to exhibit plasticity. This work expands our knowledge of how adult neural circuits react and rearrange in the face of injury and permits the design of novel psychophysics testing paradigms and ganglion cell neuroprotection or regeneration strategies.
Modelling complex retinal disease with a large scale patient induced pluripotent stem cell approach
Authors: Pebay Alice 
Published: December 2022

AbstractTo assess the transcriptomic profile of disease‐specific cell populations, fibroblasts from patients with geographic atrophy – the advanced form of age‐related macular degeneration – were reprogrammed into induced pluripotent stem cells (iPSCs) before being differentiated into retinal pigment epithelium (RPE) cells and compared to those from healthy individuals. RPE cells were subjected to single‐cell RNA‐sequencing and to mass spectrometry, to precisely characterize their transcriptomic and proteomic profiles. This approach implicated genes at loci definitively associated with disease, and uncovered new pathogenic pathways, which were subsequently confirmed by functional analysis. This work highlights the power of large‐scale iPSC studies to uncover context‐specific profiles for genetically complex disease such as age‐related macular degeneration.
Müller‐retinal ganglion cell interactions
Authors: Vecino Elena , Pereiro Xandra , Ruzafa Noelia 
Published: December 2022

AbstractGlaucoma is a neurodegenerative disease and the leading cause of irreversible blindness in the world, whose main risk factor is increased intraocular pressure. When visual problems are first detected in patients with glaucoma, already half of the retinal ganglion cells (RGCs), the neurons that send visual information from the eye to the brain, have died principally in the peripheral retina. The timeframe of cell death is prolonged, lasting even decades after an initial diagnosis. Müller glia (MG) are the main macroglial cell in the retina, play prominent roles regulating normal and pathological physiology and react to neuronal injury in glaucoma. The change to a reactive phenotype of MG initiates signalling cascades that may serve a neuroprotective role but may also proceed to promote damaging effects on RGCs. However, the underlying mechanisms and signalling pathways that specifically promote protective versus destructive roles of reactive glial cells are mostly unclear.Our main hypothesis is that MGs exert an important role in the death of RGCs in glaucoma with the MGs in the periphery being the most sensitive to intraocular pressure, promoting the death of RGCs. Preventing MG response to elevated pressure, MG can neuroprotect RGCs in early stages of glaucoma.We have proved in vitro, that in control condition MG secret neuroprotective factors, and under elevated pressure MG are the responsible for the RGCs death, being less sensitive to the elevated hydrostatic pressure (EHP) the MG present in the central retina. Moreover, stretch‐activated nonselective TRPV4 cation channels present in MG are differently activated by the pressure depending on their location within the retina. Proteomic analysis from the conditioned media (CM) of MG revealed different protein expression levels being more pronounced in the CM from MG from peripheral retina in EHP. Proteins identified correspond mainly to functions such as: apoptosis, oxidative stress, inflammation and angiogenesis.We conclude that the different sensibility of the RGCs to pressure in glaucoma could be related with the different activation of the neighbours MG.Supported by ELKARTEK (KK‐2019/00086), MINECO‐Retos (PID2019‐111139RB‐I00) and PIBA (2020_1_0026).
Amniotic membrane (AM) for ocular surface pathology: The old and the new
Authors: Herrera Josè M. 
Published: December 2022

AbstractThe first amniotic membrane use was dated in 1910 as a skin graft substitute material. In the ophthalmological field, it was first used in the 1940 s as a conjunctival substitute after removal of fibrotic tissue, with good results when it was contracted with rabbit peritoneum. The procedure lost interest because the tissue could only be used fresh. Clinicians regained interest in the early 1990 s when new preservation, storage and distribution methods were already available.Application methods: The way to use the amniotic membrane depends on the pathological situation for which it is indicated. The depth, shape and size of the recipient area also play a role in the therapeutic decision.In general, there are three possible situations:An inlay transplantation as a graft: The AM works as a replacement of the lost tissue because it is remodelled into the host corneal matrix over time. The amnion is placed epithelial side up, as the membrane is able to act as a substrate for epithelial regeneration.An onlay transplantation as a patch: The transplant acts as a temporary biological bandage. The AM and the molecules that produces, protect the cornea from environmental aggressions, and it also has antifibrotic effect. The amnion is placed epithelial side down. Usually the product can be removed, although it is usually self‐degraded.Combinatorial transplantation as a sandwich: Two layers are transplanted, the deepest is placed epithelial side up and the other epithelial side down, obtaining the benefits of the two techniques.The graft provides structural integrity and the patch gives protection to de the graft, while the epithelium is expected to grow between the two layers.From our point of view this is the best option.Main indications as a graft:‐Corneal ulcerations and persistent epithelial defects.‐Limbal Stem Cells Deficiency (LSCD). It can be used in Simple Limbal Epithelial Transplantation (SLET), in Amnion‐Assisted Epithelial Redirection (ACER), and as a matrix for Cultivated Stem Cell Transplantation.‐In Glaucoma, to treat leaks from blebs.‐In Neoplasias, AM is used to act as a substrate for conjunctival migration and reconstruction following excision of both malignant and benign tumours.‐In Oculoplastic surgery, AM has been suggested as a potential alternative to mucosal membrane transplantation in lid revision, orbital linings or symblepharolysis.‐In Pterygium surgery, mainly in relapsing cases in which a very large resection of the conjunctiva is made.‐In Strabismus surgery, either to cover defects or to reduce muscle fibrosis and adhesion.Main indications as a patch, for Ocular Surface Wound Healing:‐In the acute stage of Chemical/Thermal injuries.‐In the acute stage of Cicatrising Conjunctivitis (Erythema Multiforme Diseases, Pemphigoid, Graft versus Hosts Disease).‐In recurrent corneal erosions.The potential risks of amniotic transplantation will be discussed.
Lyophilized amniotic membrane for corneal ulcer and post operative cross‐linking
Authors: Knoeri Juliette 
Published: December 2022

AbstractPatients with progressive keratoconus, especially in the early part of life, may benefit from crosslinking to accelerate the polymerization of corneal collagen, thus increasing the biomechanical strength of the cornea. The reference crosslinking protocol, recognized as the most effective in stabilizing the disease, corresponds to a classic crosslinking protocol with de‐epithelialization (epi off). This technique is pro‐inflammatory in patients who often have associated allergic keratoconjunctivitis. It is also painful postoperatively despite the systematic application of a dressing lens since it requires corneal de‐epithelialisation. The allergic background can lead to delays in healing with postoperative infections. Amniotic membranes have already been used in post refractive surgery. Their application in post‐crosslinking protocol epi off, directly on the patient's cornea without suture under a therapeutic contact lens, would reduce the intensity of pain after the procedure, complications such as infectious keratitis, sterile infiltrates, superficial or deep haze, aseptic corneal necrosis (thinning and fibrosis, perforation described), endothelial damage due to probable excessive free radical toxicity (reversible corneal decompensation or requiring a corneal graft), delayed epithelial healing (association of dry syndrome or blepharitis) and viral reactivation (Herpes Simplex virus or HSV). The amniotic membrane by its anti‐angiogenic, healing, anti‐inflammatory and anti‐infectious properties seems to have a decrease in post‐operative pain and an acceleration of corneal epithelial healing as in superficial corneal ulcers.
Amniotic membrane as a substrate and delivery vehicle for stem cells
Authors: Calonge Margarita 
Published: December 2022

AbstractNew therapeutic concepts and clinical strategies are emerging for the different kinds of human amniotic membranes (hAM). There are new commercial forms of hAM that are under investigation for old and new applications, from ocular surface epithelial persistent defects to the hAM extract eyedrops or the new use of hAM as a delivery platform and substrate for stem cells for ocular surface repair.Although there are more substrates used as support for growth, maintenance, and delivery of cultivated stem cells onto the ocular surface, hAM is still the most used universally, followed by fibrin‐based substrates. This is due to the notable biological properties of this live tissue. The only disadvantage may be that it must come from tissue banks and as such, there can be some shortages and the cost is not irrelevant.Several other types of synthetic substrates such as lotrafilcon A, siloxane hydrogels or poly lactide‐co‐glycolic acid (PLGA) polymers, have been used over the last years to facilitate cell culture and the subsequent transplantation onto the ocular surface. In addition, several polymeric biomaterials like polycaprolactone, polylactic glycolic acid, chitosan and gelatin membranes, collagen or elastin‐like polymers are being also used to support ocular epithelial cells in preclinical studies. However, none of those attempts to substitute hAM have been translated inti clinical use.We have successfully used hAM as substrate and delivery platform in preclinical research, both in vitro and in vivo models of stem cell deficiency, and in the two clinical trials that have been completed and published, with both cultivated epithelial cells from the limbal niche and bone marrow‐derived mesenchymal stem cells.
natural treatment for dry eye disease
Authors: Messmer Elisabeth M. 
Published: December 2022

AbstractStandard recommendations for Dry Eye Disease (DED) are part of many national and international guidelines. However, many patients wish to substitute or add natural treatments to their regimen for DED. These include natural ingredients such as Manuka honey, Aloe vera, and Green Tea extract. In addition, human body ‘products’ such as autologous blood, human breast milk, urine and faeces are used in the treatment of DED. Studies evaluating these natural treatments are scarce, and information for self‐production and use are often communicated through the internet. This presentation will give an overview on existing information concerning this hot topic.
Beyond the Dresden protocol: Optimization corneal cross linking for the treatment of keratoconus
Authors: Jil Joao 
Published: December 2022

AbstractThe treatment of keratoconus (KC) was revolutionized with the introduction of corneal cross‐linking (CXL). Wollensak, Spoerl and Seiler were among the pioneers and reported the first clinical study on CXL, in what became known as the standard ‘Dresden’ protocol. Throughout the years, CXL has steadily become an established procedure globally and is currently considered the gold standard treatment for progressing keratoconus. However, despite its groundbreaking advantages and widespread clinical use, CXL as it was originally performed in the Dresden standard protocol is not without insufficiencies.One of the main drawbacks of standard CXL is its prolonged duration and its relative inability to rehabilitate vision. The irradiation process of standard CXL can be burdensome and new, shorter, irradiation protocols have been proposed. And mostly, classical CXL has been shown to cause some flattening of the irregular corneal curvature, but the refractive and visual improvements associated with it are—when present—unpredictable and uncontrollable. Other issues are related to patient selection, namely our relative inability to predict why some patients have a better biomechanical response while others show little topographic improvement or continue to progress even after CXL. This issue is particularly salient in children, who present with more aggressive cases of KC and appear to have comparatively worse outcomes after CXL. Finally, despite being relatively safe, CXL is not necessarily exempt of potential complications. Some of the most common include stromal haze and complications related with the need to remove the corneal epithelium before the procedure.At its inception, CXL completely changed how we approach the treatment of KC patients and has proved to be a momentous tool in our therapeutic arsenal. Building on those advantages, the scientific and medical community has strived to tackle some of the unmet needs we still have. How to personalize the CXL treatment protocol to find the best, most effective, and most comfortable procedure for each patient. How to improve patient screening and selection to make sure that we are providing care to those patients that can most benefit from it. And how to achieve all these goals while maintaining CXL a safe procedure.We will show how our team has tackled these various issues, share our most recent findings in this field and explore which challenges still lie ahead.
Autophagy and retinal ganglion cell death in glaucoma: Friend or foe?
Authors: Russo Rossella 
Published: December 2022

AbstractGlaucoma, a leading cause of irreversible blindness worldwide, is an age‐related neurodegenerative disease characterized by progressive alterations of the optic nerve head and degeneration of retinal ganglion cells (RGCs). Although elevated intraocular pressure (IOP) has been identified as the main and the only modifiable risk factor, the pathogenesis of the disease is still unclear. Indeed, lowering IOP is often insufficient to prevent the damage progression leaving unmet the therapeutic need of IOP‐independent pharmacological targets.Autophagy, and the more selective mitophagy, are responsible for breaking down cellular components, preserving cellular homeostasis and preventing the accumulation of altered and aggregated proteins and damaged organelles.Several evidence have shown that modulation of autophagy is a recurrent and functional response of RGCs to IOP‐dependent or independent glaucoma‐related insults. However, in RGCs, autophagy has been found to take part to either neuroprotection as well as neuronal death, depending on the experimental setting (i.e. animal model, timing of the experiments, drugs/doses used to modulate the pathway).Here we describe the dynamic changes of autophagy flux and the modulation of mitophagy related proteins in a model of acute glaucoma induced in C57BL/6J mice by transient elevation of intraocular pressure (IOP). We also report and discuss experimental evidence supporting the pro‐survival role of autophagy and mitophagy induction in mice subjected to ocular hypertension suggesting the possibility to targeting autophagy to achieve retinal neuroprotection in glaucoma.
Neuroprotection and neuroregeneration of cornea and ocular surface
Authors: Salgado‐Borges Jose Manuel 
Published: December 2022

AbstractNowadays, it is important to select the most appropriate treatment regimen for individual patients with ocular surface pathology namely dry eye disease (DED) or Meibomian Gland Dysfunction (MGD), applying to evidence‐based medicine, in order to reduce or avoid visual impairment and to improve the quality‐of‐life related to these pathologies.We shall provide an etiological therapeutic strategy to DED with special approach to the type of dry eye and to improve that approach according to inflammation and neuroprotective factors. Also, patients with DED have high levels of inflammatory molecules in the tears and ocular surface.Eye drops are the most frequent treatment for most common early cases of DED. Coenzyme Q10, present in some eye drops, can be considered a candidate for promoting the healing of the cornea—not only due to its bioenergetic effect, but also has antiapoptotic, anti‐inflammatory and antioxidant effect, which can be directly related to its neuroprotective role.For moderate cases or those not satisfactory treated with eye drops, the IPL (Intense Pulsed Light) is one of the most recent and promising option. IPL has the potential to interfere with the inflammatory cycle in DED, by upregulating anti‐inflammatory cytokines, or downregulating proinflammatory cytokines. One way to better understand the effect of IPL in DED patients would be to study the signs and clinical symptoms of these patients relating them to the changes in the genes found in their conjunctival cells, evaluating changes in gene expression related to inflammation and neuroprotection response, after treatment with IPL.Finally, an option for severe cases of DED namely neuropathic corneal lesions and/or present in immunological affected patients is ENDORET® that promotes for example refractive corneal ulcers healing. ENDORET® is an eye drop developed in the field of regenerative medicine. Basically, it is a plasma enriched in growth factors, made from the patient's own blood to promote the repair of the tissues on the surface of the eye, which stimulates cell proliferation and optimizes the processes of healing and tissue regeneration.