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Journal of Clinical Medicine Jun 2024Human cytomegalovirus (hCMV) is the most common etiological agent of congenital infections seen in newborns. Among the most commonly observed complications in children... (Review)
Review
Human cytomegalovirus (hCMV) is the most common etiological agent of congenital infections seen in newborns. Among the most commonly observed complications in children with congenital human cytomegalovirus infection are those affecting the visual system. Ocular complications of congenital CMV (cCMV) are a topic rarely addressed in the literature, which prompted the authors to update the available knowledge with the latest data. English-language literature published between April 2000 and November 2023 (PubMed, NIH, Google Scholar) was analyzed for ocular complications of cCMV. The data obtained were categorized according to the ocular area involved and the incidence. A compilation of criteria for the symptomatic form of cCMV was also created. The cCMV complications described in the literature affect all parts of the visual system: the anterior segment, the posterior segment, the posterior visual pathways, and the visual cortex. The most commonly described ocular complication of cCMV is choroidal and retinal scarring. Ophthalmic complications of cCMV can cause severe visual disturbances. Ophthalmic diagnosis in newborns should include hCMV PCR testing, which has the highest sensitivity and specificity. In the symptomatic form of cCMV, treatment should be instituted according to recommendations. A consensus should be established for screening of primary hCMV infection in pregnant women, the way in which to define the symptomatic form of cCMV, and the appropriateness and standards of treatment for primary hCMV infection in pregnant women.
PubMed: 38929909
DOI: 10.3390/jcm13123379 -
Antioxidants (Basel, Switzerland) Jun 2024Oxidative stress is a key factor causing mitochondrial dysfunction and retinal ganglion cell (RGC) death in glaucomatous neurodegeneration. The cyclic adenosine...
Oxidative stress is a key factor causing mitochondrial dysfunction and retinal ganglion cell (RGC) death in glaucomatous neurodegeneration. The cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway is involved in mitochondrial protection, promoting RGC survival. Soluble adenylyl cyclase (sAC) is a key regulator of the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway, which is known to protect mitochondria and promote RGC survival. However, the precise molecular mechanisms connecting the sAC-mediated signaling pathway with mitochondrial protection in RGCs against oxidative stress are not well characterized. Here, we demonstrate that sAC plays a critical role in protecting RGC mitochondria from oxidative stress. Using mouse models of oxidative stress induced by ischemic injury and paraquat administration, we found that administration of bicarbonate, as an activator of sAC, protected RGCs, blocked AMP-activated protein kinase activation, inhibited glial activation, and improved visual function. Moreover, we found that this is the result of preserving mitochondrial dynamics (fusion and fission), promoting mitochondrial bioenergetics and biogenesis, and preventing metabolic stress and apoptotic cell death. Notably, the administration of bicarbonate ameliorated mitochondrial dysfunction in RGCs by enhancing mitochondrial biogenesis, preserving mitochondrial structure, and increasing ATP production in oxidatively stressed RGCs. These findings suggest that activating sAC enhances the mitochondrial structure and function in RGCs to counter oxidative stress, consequently promoting RGC protection. We propose that modulation of the sAC-mediated signaling pathway has therapeutic potential acting on RGC mitochondria for treating glaucoma and other retinal diseases.
PubMed: 38929182
DOI: 10.3390/antiox13060743 -
Diagnostics (Basel, Switzerland) Jun 2024Retrograde axonal neurodegeneration along the visual pathway-either direct or trans-synaptic-has already been demonstrated in multiple sclerosis (MS), as well as in... (Review)
Review
Retrograde axonal neurodegeneration along the visual pathway-either direct or trans-synaptic-has already been demonstrated in multiple sclerosis (MS), as well as in compressive, vascular, or posttraumatic lesions of the visual pathway. Optical coherence tomography (OCT) can noninvasively track macular and optic nerve changes occurring as a result of this phenomenon. Our paper aimed to review the existing literature regarding hemimacular atrophic changes in the ganglion cell layer identified using OCT examination in MS patients without prior history of optic neuritis. Homonymous hemimacular atrophy has been described in post-chiasmal MS lesions, even in patients with normal visual field results. Temporal and nasal macular OCT evaluation should be performed separately in all MS patients, in addition to an optic nerve OCT evaluation and a visual field exam.
PubMed: 38928670
DOI: 10.3390/diagnostics14121255 -
Diagnostics (Basel, Switzerland) Jun 2024Optical coherence tomography (OCT) is a non-invasive imaging technique based on the principle of low-coherence interferometry that captures detailed images of ocular...
Optical coherence tomography (OCT) is a non-invasive imaging technique based on the principle of low-coherence interferometry that captures detailed images of ocular structures. Multiple sclerosis (MS) is a neurodegenerative disease that can lead to damage of the optic nerve and retina, which can be depicted by OCT. The purpose of this pilot study is to determine whether macular OCT can be used as a biomarker in the detection of retrochiasmal lesions of the visual pathway in MS patients. We conducted a prospective study in which we included 52 MS patients and 27 healthy controls. All participants underwent brain MRI, visual field testing, and OCT evaluation of the thicknesses of the peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell layer (GCL), and macular inner plexiform layer (IPL). OCT measurements were adjusted for optic neuritis (ON). VF demonstrated poor capability to depict a retrochiasmal lesion identified by brain MRI (PPV 0.50). In conclusion, the OCT analysis of the macula appears to excel in identifying retrochiasmal MS lesions compared to VF changes. The alterations in the GCL and IPL demonstrate the most accurate detection of retrochiasmal visual pathway changes in MS patients.
PubMed: 38928637
DOI: 10.3390/diagnostics14121221 -
Brain Sciences Jun 2024Recent evidence shows that it is possible to identify the elements responsible for sensorineural hearing loss, such as pro-inflammatory cytokines and macrophages, by... (Review)
Review
Recent evidence shows that it is possible to identify the elements responsible for sensorineural hearing loss, such as pro-inflammatory cytokines and macrophages, by performing perilymph sampling. However, current studies have only focused on the diagnosis of such as otologic conditions. Hearing loss is a feature of certain neuroinflammatory disorders such as multiple sclerosis, and sensorineural hearing loss (SNHL) is widely detected in Alzheimer's disease. Although the environment of the inner ear is highly regulated, there are several communication pathways between the perilymph of the inner ear and cerebrospinal fluid (CSF). Thus, examination of the perilymph may help understand the mechanism behind the hearing loss observed in certain neuroinflammatory and neurodegenerative diseases. Herein, we review the constituents of CSF and perilymph, the anatomy of the inner ear and its connection with the brain. Then, we discuss the relevance of perilymph sampling in neurology. Currently, perilymph sampling is only performed during surgical procedures, but we hypothesize a simplified and low-invasive technique that could allow sampling in a clinical setting with the same ease as performing an intratympanic injection under direct visual check. The use of this modified technique could allow for perilymph sampling in people with hearing loss and neuroinflammatory/neurodegenerative disorders and clarify the relationship between these conditions; in fact, by measuring the concentration of neuroinflammatory and/or neurodegenerative biomarkers and those typically expressed in the inner ear in aging SNHL, it could be possible to understand if SNHL is caused by aging or neuroinflammation.
PubMed: 38928621
DOI: 10.3390/brainsci14060621 -
Bioengineering (Basel, Switzerland) Jun 2024The purpose of the current study was to elucidate the physiological roles of intraocularly present fatty acid-binding protein 4 (FABP4). Using four representative...
The purpose of the current study was to elucidate the physiological roles of intraocularly present fatty acid-binding protein 4 (FABP4). Using four representative intraocular tissue-derived cell types, including human non-pigmented ciliary epithelium (HNPCE) cells, retinoblastoma (RB) cells, adult retinal pigment epithelial19 (ARPE19) cells and human ocular choroidal fibroblast (HOCF) cells, the intraocular origins of FABP4 were determined by qPCR analysis, and the intracellular functions of FABP4 were investigated by seahorse cellular metabolic measurements and RNA sequencing analysis using a specific inhibitor for FABP4, BMS309403. Among these four different cell types, FABP4 was exclusively expressed in HOCF cells. In HOCF cells, both mitochondrial and glycolytic functions were significantly decreased to trace levels by BMS309403 in a dose-dependent manner. In the RNA sequencing analysis, 67 substantially up-regulated and 94 significantly down-regulated differentially expressed genes (DEGs) were identified in HOCF cells treated with BMS309403 and those not treated with BMS309403. The results of Gene Ontology enrichment analysis and ingenuity pathway analysis (IPA) revealed that the DEGs were most likely involved in G-alpha (i) signaling, cAMP-response element-binding protein (CREB) signaling in neurons, the S100 family signaling pathway, visual phototransduction and adrenergic receptor signaling. Furthermore, upstream analysis using IPA suggested that NKX2-1 (thyroid transcription factor1), HOXA10 (homeobox A10), GATA2 (gata2 protein), and CCAAT enhancer-binding protein A (CEBPA) were upstream regulators and that NKX homeobox-1 (NKX2-1), SFRP1 (Secreted frizzled-related protein 1) and TREM2 (triggering receptor expressed on myeloid cells 2) were causal network master regulators. The findings in this study suggest that intraocularly present FABP4 originates from the ocular choroid and may be a critical regulator for the cellular homeostasis of non-adipocyte HOCF cells.
PubMed: 38927820
DOI: 10.3390/bioengineering11060584 -
Biomedicines May 2024Fixed appliance (FA) therapy predisposes patients to white spot lesions (WSLs). The F-ACP complex (amorphous calcium phosphate nanoparticles enriched with carbonate and...
Fixed appliance (FA) therapy predisposes patients to white spot lesions (WSLs). The F-ACP complex (amorphous calcium phosphate nanoparticles enriched with carbonate and fluorine and coated with citrate) has been effective for in vitro enamel remineralization. The aim of this study was to evaluate the efficacy of the F-ACP complex in remineralizing WSLs after FA therapy. One hundred and six adolescents (aged 12-20 years) were randomized into study and control groups after FA therapy. Patients in the study group were advised to use dental mousse containing F-ACP applied within Essix retainers for six months. The presence of WSLs was recorded at baseline (T0), 3 months (T1), and 6 months (T2) according to the International Caries Detection and Assessment System (ICDAS). Visual Plaque Index (VPI) and Gingival Bleeding Index (GBI) were recorded. Among 106 study participants, 91 (52 and 39 in study and control groups, respectively) completed the study. The results showed that the ICDAS score was significantly lower ( < 0.001) in the study group than in the control group between T0 and T2. The application of mousse containing the F-ACP complex inside Essix retainers for six months is effective in remineralizing white spot lesions in patients after FA therapy without side effects.
PubMed: 38927409
DOI: 10.3390/biomedicines12061202 -
Behavioral Sciences (Basel, Switzerland) May 2024This study examined 430 Chinese college students' engagement in arts activities and the psychological benefits derived from such activities. The research differentiated...
This study examined 430 Chinese college students' engagement in arts activities and the psychological benefits derived from such activities. The research differentiated between various types of arts participation and ways of involvement and examined four potential positive psychological outcomes. The findings revealed correlations between (1) creative participation in the performing arts, 'flow', and aesthetic emotions; (2) consumptive participation in the visual arts and aesthetic emotions; and (3) creative participation in the literary arts and ego identity. Holistic arts participation demonstrated a significantly positive relationship with flourishing. A path analysis showed that flow experience and aesthetic emotions served as mediators in the mechanism through which holistic arts participation affected flourishing, with a chained mediation effect from flow experience to ego identity. This study confirms that arts participation is an effective pathway for individual flourishing and that more diverse and profound engagement in the arts can lead to sustained and widespread happiness.
PubMed: 38920780
DOI: 10.3390/bs14060448 -
Journal of Neuroinflammation Jun 2024The microglia-mediated neuroinflammation have been shown to play a crucial role in the ocular pathological angiogenesis process, but specific immunotherapies for...
The microglia-mediated neuroinflammation have been shown to play a crucial role in the ocular pathological angiogenesis process, but specific immunotherapies for neovascular ocular diseases are still lacking. This study proposed that targeting GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) might be a novel immunotherapy for these angiogenesis diseases. We found a significant upregulation of CGAS and STING genes in the RNA-seq data derived from retinal tissues of the patients with proliferative diabetic retinopathy. In experimental models of ocular angiogenesis including laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR), the cGAS-STING pathway was activated as angiogenesis progressed. Either genetic deletion or pharmacological inhibition of STING resulted in a remarkable suppression of neovascularization in both models. Furthermore, cGAS-STING signaling was specifically activated in myeloid cells, triggering the subsequent RIP1-RIP3-MLKL pathway activation and leading to necroptosis-mediated inflammation. Notably, targeted inhibition of the cGAS-STING pathway with C-176 or SN-011 could significantly suppress pathological angiogenesis in CNV and OIR. Additionally, the combination of C-176 or SN-011 with anti-VEGF therapy led to least angiogenesis, markedly enhancing the anti-angiogenic effectiveness. Together, our findings provide compelling evidence for the importance of the cGAS-STING-necroptosis axis in pathological angiogenesis, highlighting its potential as a promising immunotherapeutic target for treating neovascular ocular diseases.
Topics: Nucleotidyltransferases; Membrane Proteins; Animals; Humans; Mice; Neuroinflammatory Diseases; Mice, Inbred C57BL; Choroidal Neovascularization; Signal Transduction; Mice, Knockout; Diabetic Retinopathy
PubMed: 38918759
DOI: 10.1186/s12974-024-03155-y -
Advances in Experimental Medicine and... 2024Temporal information processing in the range of a few hundred milliseconds to seconds involves the cerebellum and basal ganglia. In this chapter, we present recent... (Review)
Review
Temporal information processing in the range of a few hundred milliseconds to seconds involves the cerebellum and basal ganglia. In this chapter, we present recent studies on nonhuman primates. In the studies presented in the first half of the chapter, monkeys were trained to make eye movements when a certain amount of time had elapsed since the onset of the visual cue (time production task). The animals had to report time lapses ranging from several hundred milliseconds to a few seconds based on the color of the fixation point. In this task, the saccade latency varied with the time length to be measured and showed stochastic variability from one trial to the other. Trial-to-trial variability under the same conditions correlated well with pupil diameter and the preparatory activity in the deep cerebellar nuclei and the motor thalamus. Inactivation of these brain regions delayed saccades when asked to report subsecond intervals. These results suggest that the internal state, which changes with each trial, may cause fluctuations in cerebellar neuronal activity, thereby producing variations in self-timing. When measuring different time intervals, the preparatory activity in the cerebellum always begins approximately 500 ms before movements, regardless of the length of the time interval being measured. However, the preparatory activity in the striatum persists throughout the mandatory delay period, which can be up to 2 s, with different rate of increasing activity. Furthermore, in the striatum, the visual response and low-frequency oscillatory activity immediately before time measurement were altered by the length of the intended time interval. These results indicate that the state of the network, including the striatum, changes with the intended timing, which lead to different time courses of preparatory activity. Thus, the basal ganglia appear to be responsible for measuring time in the range of several hundred milliseconds to seconds, whereas the cerebellum is responsible for regulating self-timing variability in the subsecond range. The second half of this chapter presents studies related to periodic timing. During eye movements synchronized with alternating targets at regular intervals, different neurons in the cerebellar nuclei exhibit activity related to movement timing, predicted stimulus timing, and the temporal error of synchronization. Among these, the activity associated with target appearance is particularly enhanced during synchronized movements and may represent an internal model of the temporal structure of stimulus sequence. We also considered neural mechanism underlying the perception of periodic timing in the absence of movement. During perception of rhythm, we predict the timing of the next stimulus and focus our attention on that moment. In the missing oddball paradigm, the subjects had to detect the omission of a regularly repeated stimulus. When employed in humans, the results show that the fastest temporal limit for predicting each stimulus timing is about 0.25 s (4 Hz). In monkeys performing this task, neurons in the cerebellar nuclei, striatum, and motor thalamus exhibit periodic activity, with different time courses depending on the brain region. Since electrical stimulation or inactivation of recording sites changes the reaction time to stimulus omission, these neuronal activities must be involved in periodic temporal processing. Future research is needed to elucidate the mechanism of rhythm perception, which appears to be processed by both cortico-cerebellar and cortico-basal ganglia pathways.
Topics: Animals; Cerebellum; Basal Ganglia; Time Perception; Saccades; Time Factors; Humans
PubMed: 38918348
DOI: 10.1007/978-3-031-60183-5_6