In vitro model of reconstructed human corneal epithelium for the evaluation of ocular surface desiccation and protection with vitamin A enriched ophthalmic ointment.

The aim of this study was to evaluate the efficacy of a paraffin ointment enriched with vitamin A in the protection against severe desiccation using 2D and 3D corneal epithelial in vitro models. We used immortalized human corneal epithelial cell cultures to evaluate the efficacy of four compounds -a paraffin ointment enriched with vitamin A (vA-PFF) and its vehicle; an aqueous gel containing hydroxypropyl guar (HPG); and an aqueous gel containing sodium carboxymethylcellulose (CMC)- to preserve cell viability in an in vitro model of desiccation. WST-1 and Live/Dead assays were used to study cell viability.

Comprehensive Evaluation of the Genetic Basis of Keratoconus: New Perspectives for Clinical Translation.

Purpose: Keratoconus (KC) is a corneal disorder with complex etiology, apparently involving both genetic and environmental factors, characterized by progressive thinning and protrusion of the cornea. We aimed to identify novel genetic regions associated with KC susceptibility, elucidate relevant genes for disease development, and explore the translational implications for therapeutic intervention and risk assessment.

Methods: We conducted a genome-wide association study (GWAS) that integrated previously published data with newly generated genotyping data from an independent European cohort.

Efficacy and Safety of Plasma Rich in Growth Factor in Patients with Congenital Aniridia and Dry Eye Disease.

Unlabelled: Congenital aniridia is a rare bilateral ocular malformation characterized by the partial or complete absence of the iris and is frequently associated with various anomalies, including keratopathy, cataract, glaucoma, and foveal and optic nerve hypoplasia. Additionally, nearly 50% of individuals with congenital aniridia experience symptoms of ocular dryness. Traditional treatment encompasses artificial tears and autologous serum.

Immunocytochemical Analysis of Crocin against Oxidative Stress in Trigeminal Sensory Neurons Innervating the Cornea.

Corneal diseases are a major cause of vision loss, often associated with aging, trauma and disease. Damage to corneal sensory innervation leads to discomfort and pain. Environmental stressors, such as short-wavelength light, can induce oxidative stress that alters mitochondrial function and affects cell and tissue homeostasis, including corneal innervation.

Altered Clock Gene Expression in Female APP/PS1 Mice and Aquaporin-Dependent Amyloid Accumulation in the Retina.

Alzheimer's disease (AD), the most prevalent form of dementia, is a neurodegenerative disorder characterized by different pathological symptomatology, including disrupted circadian rhythm. The regulation of circadian rhythm depends on the light information that is projected from the retina to the suprachiasmatic nucleus in the hypothalamus. Studies of AD patients and AD transgenic mice have revealed AD retinal pathology, including amyloid-β (Aβ) accumulation that can directly interfere with the regulation of the circadian cycle.

Impact of Plasma Rich in Growth Factors (PRGF) Eye Drops on Ocular Redness and Symptomatology in Patients with Dry Eye Disease.

: Dry eye disease (DED) is a common and very symptomatic pathology that affects normal daily activity. The aim of the study was to evaluate the efficacy of plasma rich in growth factors (PRGF) added to one routine treatment protocol for DED (artificial tears substitutes, lid hygiene, and anti-inflammatory therapy). : Patients were divided into two groups of treatment: standard treatment group ( = 43 eyes) and PRGF group ( = 59).

Disturbed circadian rhythm and retinal degeneration in a mouse model of Alzheimer's disease.

The circadian clock is synchronized to the 24 h day by environmental light which is transmitted from the retina to the suprachiasmatic nucleus (SCN) primarily via the retinohypothalamic tract (RHT). Circadian rhythm abnormalities have been reported in neurodegenerative disorders such as Alzheimer's disease (AD). Whether these AD-related changes are a result of the altered clock gene expression, retina degeneration, including the dysfunction in RHT transmission, loss of retinal ganglion cells and its electrophysiological capabilities, or a combination of all of these pathological mechanisms, is not known.

Recovery of Corneal Innervation after Treatment in Dry Eye Disease: A Confocal Microscopy Study.

Purpose: To analyze the changes in corneal innervation by means of in vivo corneal confocal microscopy (IVCM) in patients diagnosed with Evaporative (EDE) and Aqueous Deficient Dry Eye (ADDE) and treated with a standard treatment for Dry Eye Disease (DED) in combination with Plasma Rich in Growth Factors (PRGF).

Methods: Eighty-three patients diagnosed with DED were enrolled in this study and included in the EDE or ADDE subtype. The primary variables analyzed were the length, density and number of nerve branches, and the secondary variables were those related to the quantity and stability of the tear film and the subjective response of the patients measured with psychometric questionnaires.

Improved Tool for Predicting Skin Irritation on Reconstructed Human Epidermis Models Based on Electrochemical Impedance Spectroscopy.

The rabbit skin irritation test has been the standard for evaluating the irritation potential of chemicals; however, alternative methods that do not use animal testing are actively encouraged. Reconstructed human epidermis (RhE) models mimic the biochemical and physiological properties of the human epidermis and can be used as an alternative method. On RhE methods, the metabolic activity of RhE models is used to predict skin irritation, with a reduction in metabolic activity indicating a reduced number of viable cells and linking cell death to skin irritation processes.

Synthetic Heparan Sulfate Mimetic Polymer Enhances Corneal Nerve Regeneration and Wound Healing after Experimental Laser Ablation Injury in Mice.

(1) Background: Abnormal corneal wound healing compromises visual acuity and can lead to neuropathic pain. Conventional treatments usually fail to restore the injured corneal tissue. In this study, we evaluated the effectiveness of a synthetic heparan sulfate mimetic polymer (HSmP) in a mouse model of corneal wound healing.

Exosomes Released by Corneal Stromal Cells Show Molecular Alterations in Keratoconus Patients and Induce Different Cellular Behavior.

Exosomes have been related to various disorders, but their study in relation to ocular pathologies has been limited. In this article, we analyze exosomes produced by corneal stromal cells from healthy individuals and from patients with keratoconus. The proteomic study allowed for the identification of 14 new proteins with altered expression, related to molecules previously associated with the pathology.

Cell Surface Glycosaminoglycans as Receptors for Adhesion of spp. to Corneal Cells.

The most common causal agents of fungal keratitis are yeasts of the genus. Adhesion constitutes the first stage of pathogenesis. Previous studies have shown that glycosaminoglycans from the corneal cell surface play an essential role in bacterial keratitis, although little is known about their role in fungal infections.

In-house performance assessment of 3D QobuR-Reconstructed Human Cornea-Like Epithelium (RhCE) for the evaluation of eye hazard.

To replace the Draize eye irritation test (OECD Test Guideline 404), several test methods based on reconstructed cornea-like epithelium (RhCE) have been developed and adopted in the OECD TG 492. The objective of this study was to stablish the experimental procedures and evaluate the performance assessment of QobuR-RhCE, an in-house RhCE model to be used for the evaluation of eye hazard. We define the essential structural, functional and procedural elements of the test method components to help assuring that the proposed test method is based on the same concepts as the validated reference methods.

Polymerizable Skin Hydrogel for Full Thickness Wound Healing.

The skin is the largest organ in the human body, comprising the main barrier against the environment. When the skin loses its integrity, it is critical to replace it to prevent water loss and the proliferation of opportunistic infections. For more than 40 years, tissue-engineered skin grafts have been based on the in vitro culture of keratinocytes over different scaffolds, requiring between 3 to 4 weeks of tissue culture before being used clinically.

Human Stem Cell Transplantation for Retinal Degenerative Diseases: Where Are We Now?

: Irreversible visual impairment is mainly caused by retinal degenerative diseases such as age-related macular degeneration and retinitis pigmentosa. Stem cell research has experienced rapid progress in recent years, and researchers and clinical ophthalmologists are trying to implement this promising technology to treat retinal degeneration. The objective of this systematic review is to analyze currently available data from clinical trials applying stem cells to treat human retinal diseases.

Small fiber neuropathy in the cornea of Covid-19 patients associated with the generation of ocular surface disease.

Purpose: To describe the association between Sars-CoV-2 infection and small fiber neuropathy in the cornea identified by in vivo corneal confocal microscopy.

Methods: Twenty-three patients who had overcome COVID-19 were recruited to this observational retrospective study. Forty-six uninfected volunteers were also recruited and studied as a control group.

Alterations in the Expression of the Genes Responsible for the Synthesis of Heparan Sulfate in Brains With Alzheimer Disease.

The saccharide chains of heparan sulfate appear to be involved in several aspects Alzheimer disease (AD) pathogenesis. Their structural complexity is due to the expression of different isoenzymes. We studied the differential transcription of heparan sulfate chain biosynthesis in AD brains, analyzing different brain regions in patients with different extents of AD pathology.

Development and Optimization of Freeze-Dried Eye Drops Derived From Plasma Rich in Growth Factors Technology.

Purpose: To investigate whether plasma rich in growth factors (PRGF) eye drops maintain their biological potential after a freeze drying process. The addition of a lyoprotectant like trehalose was also evaluated.

Methods: Blood from three healthy donors was collected to obtain eye drops by PRGF technology.

Could structural changes in the retinal layers be a new biomarker of mental disorders? A systematic review and thematic synthesis.

It has recently been suggested that alterations of the layers of the retina could be a biomarker of specific mental disorders since they originate in the same embryonic layer as the brain and both are interconnected through the optic nerve. The purpose of this article is to offer a systematic review of the literature and a thematic synthesis on the current state of the alterations of the retina layers identified by optical coherence tomography in patients with schizophrenia, bipolar disorder and major depression. For this purpose, we performed a bibliographic search, a systematic review of the studies and a thematic synthesis of the reported findings.

Functional and Morphologic Alterations in Mechanical, Polymodal, and Cold Sensory Nerve Fibers of the Cornea Following Photorefractive Keratectomy.

Purpose: To define the characteristics and time course of the morphologic and functional changes experienced by corneal sensory nerves after photorefractive keratectomy (PRK).

Methods: Unilateral corneal excimer laser photoablation was performed in 54 anesthetized 3- to 6-month-old mice; 11 naïve animals served as control. Mice were killed 0, 3, 7, 15, and 30 days after PRK.

Morphological and functional changes in TRPM8-expressing corneal cold thermoreceptor neurons during aging and their impact on tearing in mice.

Morphological and functional alterations of peripheral somatosensory neurons during the aging process lead to a decline of somatosensory perception. Here, we analyze the changes occurring with aging in trigeminal ganglion (TG), TRPM8-expressing cold thermoreceptor neurons innervating the mouse cornea, which participate in the regulation of basal tearing and blinking and have been implicated in the pathogenesis of dry eye disease (DED). TG cell bodies and axonal branches were examined in a mouse line (TRPM8 -EYFP) expressing a fluorescent reporter.

Heparanase Overexpresses in Keratoconic Cornea and Tears Depending on the Pathologic Grade.

Background: Keratoconus has classically been defined as a noninflammatory disorder, although recent studies show elevated levels of inflammatory markers suggesting that keratoconus could be, at least in part, an inflammatory condition. Heparanase upregulation has been described in multiple inflammatory disorders. In this article, we study the differential expression of heparanase in cornea and tears from keratoconus patients and healthy controls.

Adipose Derived Stem Cells for Corneal Wound Healing after Laser Induced Corneal Lesions in Mice.

The aim of our study was to assess the clinical effectiveness of topical adipose derived stem cell (ADSC) treatment in laser induced corneal wounds in mice by comparing epithelial repair, inflammation, and histological analysis between treatment arms. Corneal lesions were performed on both eyes of 40 mice by laser induced photorefractive keratectomy. All eyes were treated with topical azythromycin bid for three days.

Assessing the brain through the eye: New ways to explore hepatic encephalopathy.

Background & Aims: Minimal hepatic encephalopathy (mHE) has been shown to affect daily functioning, quality of life, driving and overall mortality. However, little is known about treating or diagnosing early impairments in mHE. We studied one of its precipitating factors, portal hypertension which is driving the inflammatory process behind mHE.

Different Use of Cell Surface Glycosaminoglycans As Adherence Receptors to Corneal Cells by Gram Positive and Gram Negative Pathogens.

The epithelium of the cornea is continuously exposed to pathogens, and adhesion to epithelial cells is regarded as an essential first step in bacterial pathogenesis. In this article, the involvement of glycosaminoglycans in the adhesion of various pathogenic bacteria to corneal epithelial cells is analyzed. All microorganisms use glycosaminoglycans as receptors, but arranged in different patterns depending on the Gram-type of the bacterium.