Disrupted Neural Regeneration in Dry Eye Secondary to Ankylosing Spondylitis - With a Theoretical Link between Piezo2 Channelopathy and Gateway Reflex, WDR Neurons, and Flare-Ups

This study aimed at analyzing the corneal neural regeneration in ankylosing spondylitis patients using in vivo corneal confocal microscopy in correlation with Langerhans cell density, morphology, and dry eye parameters. Approximately 24 ankylosing spondylitis subjects and 35 age- and gender-matched control subjects were enrolled. Data analysis showed that all corneal nerve-fiber descriptives were lower in the ankylosing spondylitis group, implicating disrupted neural regeneration. Peripheral Langerhans cell density showed a negative correlation with nerve fiber descriptions. A negative correlation between tear film break-up time and corneal nerve fiber total branch density was detected. The potential role of somatosensory terminal Piezo2 channelopathy in the pathogenesis of dry eye disease and ankylosing spondylitis is highlighted in our study, exposing the neuroimmunological link between these diseases. We hypothesized earlier that spinal neuroimmune-induced sensitization due to this somatosensory terminal primary damage could lead to Langerhans cell activation in the cornea, in association with downregulated Piezo1 channels on these cells. This activation could lead to a Th17/Treg imbalance in dry eye secondary to ankylosing spondylitis. Hence, the corneal Piezo2 channelopathy-induced impaired Piezo2-Piezo1 crosstalk could explain the disrupted neural regeneration. Moreover, the translation of our findings highlights the link between Piezo2 channelopathy-induced gateway to pathophysiology and the gateway reflex, not to mention the potential role of spinal wide dynamic range neurons in the evolution of neuropathic pain and the flare-ups in ankylosing spondylitis and dry eye disease

A kortikoszteroidtartalmú szemcseppek alkalmazása gyermekkori allergiás szembetegségek kezelésében = Application of corticosteroid eye drops for allergic eye diseases in children

Absztrakt: Napjainkban az allergiás megbetegedések száma folyamatosan emelkedik. Az atópiás betegeknél gyakran jelentkeznek szemet érintő allergiás megbetegedések (szezonális és perennialis allergiás kötőhártya-gyulladás, vernalis keratoconjunctivitis, atópiás keratoconjunctivitis, óriás papillás kötőhártya-gyulladás, kontaktblepharoconjunctivitis). Az allergiás szembetegségek kezelésében szemcsepp formájában használt gyógyszerek közé tartoznak az antihisztaminok, a hízósejtmembrán-stabilizálók, a kettős támadáspontú szerek, az érösszehúzók és a kortikoszteroidok. Egyes esetekben szisztémásan antihisztaminok is használhatók. A kezelés látszólag egyszerű, a helytelen terápia azonban – szélsőséges esetben – akár látásvesztéshez is vezethet. A szemtünetek enyhítésében a kortikoszteroidok kiváló gyógyszernek számítanak, de használatuk jelentős figyelmet igényel mind a kezelőorvos, mind a beteg részéről, hiszen súlyos mellékhatásaik vannak. Ezek közül a látást leginkább veszélyeztető elváltozások a szteroidindukált szürke hályog és a még súlyosabb szteroidindukált glaukóma. Felnőttek körében e két kórkép jellemzőit, előfordulási gyakoriságát és kockázati tényezőit részletesen tanulmányozták, ellenben gyermekek esetében igen kevés irodalmi adat áll rendelkezésünkre a szteroidszemcsepp mellékhatásaival kapcsolatosan. Az eddigi tanulmányok alapján gyermekeknél sokkal nagyobb arányban alakulnak ki mellékhatások a szteroidterápia mellett, mint felnőttek körében. Orv Hetil. 2019; 160(9): 329–337. | Abstract: The prevalence of allergic diseases has been increasing recently. Allergy has various symptoms. Allergic eye diseases (seasonal and perennial allergic conjunctivitis, vernal keratoconjunctivitis, atopic keratoconjunctivitis, giant papillary conjunctivitis, contact blepharoconjunctivitis) are common in atopic patients. Treatment options for allergic conjunctivitis include local and systemic antihistamines, mast cell stabilizers, dual-action agents, vasoconstrictors and corticosteroids. Treatment seems easy, but inappropriate therapy – in extreme cases – can lead to vision loss. Corticosteroid eyedrops provide effective relief of symptoms, however, their use is limited due to their severe side effects. Both steroid-induced cataract and steroid-induced glaucoma are dangerous for vision. The characteristics, frequency and risks of these side effects have been studied widely in adults, but there are very few studies focused on children. According to the present studies, the side effects of topically administered corticosteroids appear more often in children than in adults. Orv Hetil. 2019; 160(9): 329–337

Sejtszintű képalkotás a retina in vivo vizsgálatában: jelen és jövő = In vivo cellular imaging of the retina: present and future

Összefoglaló. A látószerv különböző betegségei, valamint egyes szisztémás megbetegedések részben vagy kifejezetten az ideghártya károsodásával járnak. A patológia segítségével ma már tudjuk, hogy ezek a betegségek a retina mely rétegének vagy rétegeinek elváltozásait okozzák: míg az időskori maculadegeneratio a külső retinában található fotoreceptorokat érinti kifejezetten a fovea centralis területén, addig a glaucoma a belső retina ganglionsejtjeinek pusztulásával, valamint e sejtek opticusrostjainak károsodásával jár a stratum ganglionaréban és a stratum neurofibrarumban. Az emberi retina sejtjei azonban egyelőre nem maradéktalanul karakterizáltak, az egyes sejttípusok számát csak becsülni tudjuk, így nem írhatók le az egyes sejtszintű elváltozások sem kellő pontossággal. A szövettani feldolgozás és vizsgálat megfelelő részletességgel tájékoztat a diagnózisról és az elváltozás súlyosságáról, értelemszerűen azonban ez a módszer in vivo nem használható a mindennapi klinikai gyakorlatban. A sejtszintű elváltozások ismerete az egyes kórképekben felvetette és szükségessé tette olyan in vivo, a klinikumban is alkalmazható vizsgálómódszerek kifejlesztését, amelyek lehetőséget nyújtanak a retina neurális és egyéb sejtjeinek celluláris és szubcelluláris szintű vizsgálatára, ideértve a vér alakos elemeit is, amelyek egészséges vagy neovascularis eredetű erekben áramlanak. A jelenleg is használt klinikai vizsgálatok mellett ezek a képalkotó módszerek segítségül szolgálhatnak a diagnózis megerősítésében vagy elvetésében, emellett az elváltozás súlyosságának megítélésében, valamint a progresszió vagy remisszió monitorozásában. Orv Hetil. 2021; 162(22): 851-860. Summary. Diseases of the visual system as well as many systemic illnesses are usually associated with retinal damage. With the help of pathology, we can clearly identify the affected layer(s): while age-related macular degeneration mostly damages the photoreceptors in the outer retina at the central fovea, glaucoma promotes ganglion cell death in the ganglion cell layer and damages respective neural fibers. However, the diverse cell types of the human retina have not been fully characterized yet, thus in most cases our knowledge on cellular pathologies is not precise enough. While histopathological preparation and examination of the retinal tissue provide more detailed information about the diagnosis and the severity of the condition, unfortunately, it cannot be used in vivo in everyday clinical practice. Our understanding of the cellular changes in different diseases has revealed a need for new everyday clinical examination methods that can be used in vivo to asses cellular and subcellular changes in neural and other cells of the retina, such as blood cells flowing in healthy vessels or in vessels of neovascular origin. In addition to the currently used clinical examination methods, these imaging methods could help confirm or dismiss diagnoses, assess the severity of a condition, and monitor disease progression or remission. Orv Hetil. 2021; 162(22): 851-860

Effect of liposomal formulation of ascorbic acid on corneal permeability

Ascorbic acid (AA) has a pivotal role in corneal wound healing via stimulating the biosynthesis of highly organized extracellular matrix components, but its rapid degradation and low corneal permeability limits its therapeutic effects. In this paper, we present the pharmacokinetic properties of a liposomal-based formulation of AA in terms of corneal permeation. Chemical stability, shelf-life, and drug release rate of lyophilized liposome (AA-LLipo) formulation was determined in comparison to free-form of AA solution using high-performance liquid chromatography (HPLC) and rapid equilibrium dialysis. In vitro transcorneal permeability was studied using a parallel artificial membrane permeability assay (PAMPA). Ex vivo permeation was examined on AA-LLipo-treated porcine cornea by determining the AA content on the ocular surface, in the cornea as well as in the aqueous humor using HPLC, and by Raman-mapping visualizing the AA-distribution. Our results showed that the liposomal formulation improved the chemical stability of AA, while drug release was observed with the same kinetic efficiency as from the free-form of AA solution. Both corneal-PAMPA and porcine corneal permeability studies showed that AA-LLipo markedly improved the corneal absorption kinetics of AA, thus, increasing the AA content in the cornea and aqueous humor. AA-LLipo formulation could potentially increase the bioavailability of AA in corneal tissues

Corneal Densitometry and In Vivo Confocal Microscopy in Patients with Monoclonal Gammopathy—Analysis of 130 Eyes of 65 Subjects

Background: Corneal imaging may support an early diagnosis of monoclonal gammopathy. The goal of our study was to analyze corneal stromal properties using Pentacam and in vivo confocal cornea microscopy (IVCM) in subjects with monoclonal gammopathy. Patients and methods: In our cross-sectional study, patients with monoclonal gammopathy (130 eyes of 65 patients (40.0% males; age 67.65 ± 9.74 years)) and randomly selected individuals of the same age group, without hematological disease (100 eyes of 50 control subjects (40.0% males; age 60.67 ± 15.06 years)) were included. Using Pentacam (Pentacam HR; Oculus GmbH, Wetzlar, Germany), corneal stromal light scattering values were obtained (1) centrally 0–2 mm zone; (2) 2–6 mm zone; (3) 6–10 mm zone; (4) 10–12 mm zone. Using IVCM with Heidelberg Retina Tomograph with Rostock Cornea Module (Heidelberg Engineering, Heidelberg, Germany), the density of hyperreflective keratocytes and the number of hyperreflective spikes per image were manually analyzed, in the stroma. Results: In the first, second and third annular zone, light scattering was significantly higher in subjects with monoclonal gammopathy, than in controls (p ≤ 0.04). The number of hyperreflective keratocytes and hyperreflective spikes per image was significantly higher in stroma of subjects with monoclonal gammopathy (p ≤ 0.012). Conclusions: Our study confirms that increased corneal light scattering in the central 10 mm annular zone and increased keratocyte hyperreflectivity may give rise to suspicion of monoclonal gammopathy. As corneal light scattering is not increased at the limbal 10–12 mm annular zone in monoclonal gammopathy subjects, our spatial analysis provides evidence against the limbal origin of corneal paraprotein deposition. Using IVCM, stromal hyperreflective spikes may represent specific signs of monoclonal gammopathy

Evaluation of Retinal Blood Flow in Patients with Monoclonal Gammopathy Using OCT Angiography

Background: Monoclonal gammopathy (MG) is characterized by monoclonal protein overproduction, potentially leading to the development of hyperviscosity syndrome. Objective: To assess retinal circulation using optical coherence tomography angiography (OCTA) parameters in patients with monoclonal gammopathy. Methods: OCTA measurements were performed using the Optovue AngioVue system by examining 44 eyes of 27 patients with MG and 62 eyes of 36 control subjects. Superficial and deep retinal capillary vessel density (VD SVP and DVP) in the whole 3 × 3 mm macular and parafoveal area, foveal avascular zone (FAZ) area, and central retinal thickness (CRT) were measured using the AngioAnalytics software. The OCTA parameters were evaluated in both groups using a multivariate regression model, after controlling for the effect of imaging quality (SQ). Results: There was no significant difference in age between the subjects with monoclonal gammopathy and the controls (63.59 ± 9.33 vs. 58.01 ± 11.46 years; p > 0.05). Taking into account the effect of image quality, the VD SVP was significantly lower in the MG group compared to the control group (44.54 ± 3.22% vs. 46.62 ± 2.84%; p < 0.05). No significant differences were found between the two groups regarding the other OCTA parameters (p > 0.05). Conclusions: A decreased superficial retinal capillary vessel density measured using OCTA in patients with MG suggests a slow blood flow, reduced capillary circulation, and consequent tissue hypoperfusion. An evaluation of retinal circulation using OCTA in cases of monoclonal gammopathy may be a sensitive method for the non-invasive detection and follow-up of early microcirculatory dysfunction caused by increased viscosity

The nonstop decay and the RNA silencing systems operate cooperatively in plants

Translation-dependent mRNA quality control systems protect the protein homeostasis of eukaryotic cells by eliminating aberrant transcripts and stimulating the decay of their protein products. Although these systems are intensively studied in animals, little is known about the translation-dependent quality control systems in plants. Here, we characterize the mechanism of nonstop decay (NSD) system in Nicotiana benthamiana model plant. We show that plant NSD efficiently degrades nonstop mRNAs, which can be generated by premature polyadenylation, and stop codon-less transcripts, which are produced by endonucleolytic cleavage. We demonstrate that in plants, like in animals, Pelota, Hbs1 and SKI2 proteins are required for NSD, supporting that NSD is an ancient and conserved eukaryotic quality control system. Relevantly, we found that NSD and RNA silencing systems cooperate in plants. Plant silencing predominantly represses target mRNAs through endonucleolytic cleavage in the coding region. Here we show that NSD is required for the elimination of 5' cleavage product of mi- or siRNA-guided silencing complex when the cleavage occurs in the coding region. We also show that NSD and nonsense-mediated decay (NMD) quality control systems operate independently in plants