Nerve Fibers Research Articles

Optical Coherence Tomography Angiography Analysis of Peripapillary Choroidal Microvascular Density in normal-tension Glaucoma and Primary open-angle Glaucoma.

Glaucoma patients had a reduction in the inner annulus peripapillary choroidal microvascular density (PCMD) that became worse as the glaucoma severity progressed, which might provide new evidence supporting the vascular theory. To compare PCMD among normal-tension glaucoma (NTG), primary open-angle glaucoma (POAG), and healthy controls using optical coherence tomography (OCT) angiography (OCTA). The study included 40 POAG, 25 NTG, and 33 healthy controls. All subjects underwent OCT and OCTA testing. Inner annulus and outer annulus PCMD, as well as peripapillary vessel density (VD), was calculated. One-way analysis of variance was used to compare the vascular parameters of the three groups. Pearson correlation analysis or Spearman correlation test was used to evaluate the correlation between PCMD and glaucomatous severity factors. The spatial positional relationship between PCMD and corresponding peripapillary retinal nerve fiber layer (RNFL) thickness and visual field (VF) mean deviation (MD) was also assessed. The average and four quadrants of the inner annulus PCMD and peripapillary VD in the two glaucomatous groups were significantly lower than in normal eyes (P<0.05). Strong correlations were found between inner annulus PCMD and VF MD, peripapillary VD, and RNFL in POAG patients. Similarly, the inner annulus PCMD in NTG patients was strongly correlated with peripapillary VD and RNFL (all r>0.5). Strong positional correlations were found between inner superior quadrantal PCMD and RNFL thickness in both POAG and NTG patients (r=0.566, r=0.731, respectively). Likewise, inner inferior quadrantal PCMD exhibited a strong correlation with RNFL thickness in POAG patients (r=0.608). Strong positional correlations were also found between inner superior PCMD and VF MD in both POAG and NTG patients (r=0.589, r=0.622, respectively). Inner inferior PCMD exhibited a moderate correlation with VF MD in both POAG and NTG patients (r=0.487, r=0.440, respectively). The study found that the inner annulus PCMD decreased to varying degrees in NTG and POAG patients. The inner annulus PCMD was closely related to the structural and visual function parameters of glaucoma in both NTG and POAG. Furthermore, inner PCMD demonstrated a spatial correlation with corresponding RNFL thickness and VF MD.

Peripapillary choroidal vascularity of paediatric myopic eyes with peripapillary hyperreflective ovoid mass-like structures.

To assess the peripapillary choroidal vasculature in paediatric myopic patients with and without peripapillary hyperreflective ovoid mass-like structures (PHOMS). This prospective study includes 60 eyes of 60 myopic (spherical equivalent [SE] <-1.00 dioptre [D]) patients with (n = 30) and without (n = 30) PHOMS (PHOMS [+] and PHOMS [-] groups, respectively), and 30 eyes of 30 age- and sex-matched emmetropic children (control group). Peripapillary choroidal parameters, including total choroidal (TCA), luminal (LA), and stromal areas (SA) and choroidal vascularity index (CVI) calculated from vertical and horizontal single-line enhanced depth imaging-optical coherence tomography scans centred on optic nerve head. Peripapillary retinal nerve fibre layer thicknesses were not different between the groups (p > 0.05). In the PHOMS (+) group, TCA, LA and SA were lower, and CVI was higher in all quadrants compared to the control (p < 0.05). However, only the mean TCA and LA in the inferior and nasal quadrants and the mean SA in the nasal quadrant were lower in PHOMS (+) than in PHOMS (-) (p < 0.05). In the PHOMS (-) group, higher CVI was observed in all quadrants except temporal compared to the control group. Although the mean CVI of the PHOMS (+) group was also higher than in the PHOMS (-) group, this difference was not statistically significant. This study indicates that choroidal parameters differ in paediatric myopic patients with PHOMS. Further studies with larger sample sizes are needed to understand the details of choroidal parameters in eyes with PHOMS.

Peripheral Nerve Injury After Deoxycholic Acid (ATX-101) Injection in an Experimental Rat Model.

Deoxycholic acid (ATX-101) is a drug administered by subcutaneous injection for local fat reduction. However, ATX-101 treatment has been reported to cause marginal mandibular nerve injury with noticeable functional deficits when targeting submental fat. As a cytolytic agent with some selectivity for adipocytes, ATX-101 may damage the lipid-rich myelin surrounding peripheral nerves. This study seeks to characterize the nerve injection injury from ATX-101 in an experimental rat model. Using a rat sciatic nerve injection model, intrafascicular and extrafascicular injections of deoxycholic acid (ATX-101) were compared to lidocaine (positive control) and saline (negative control). Nerves were harvested at a 2-week endpoint for histomorphometric analysis. Cross-sectional area of nerve injury was significantly increased by ATX-101 injection at 75±15% with intrafascicular ATX-101 (p<0.001), 41±21% with extrafascicular ATX-101 (p<0.01), and 38±20% with positive control lidocaine (p<0.01) compared to 7±13% with negative control saline. Demyelinating injury was a significant mechanism of injury in the affected nerve fibers compared to uninjured nerve fibers (p<0.04), but there was no difference in axon-to-myelin area ratio between the lidocaine and ATX-101 cohorts. After two weeks, Wallerian degeneration was evident with only small regenerating nerve fibers present in the ATX-101-injured groups compared to saline (2.54±0.26um vs 5.03±0.44um, p<0.001) in average width. Deoxycholic acid (ATX-101) is capable of extensive nerve injury in rats. The mechanism of action for ATX-101 does not preferentially target myelin more than other common neurotoxic agents. Appropriate knowledge of surgical anatomy and injection technique is necessary for any practitioners providing ATX-101 injections.

Transcriptomic and histological characterization of telocytes in the human dorsal root ganglion.

Telocytes are interstitial cells with long processes that cover distances in tissues and likely coordinate interacts with other cell types. Though present in central and peripheral neuronal tissues, their role remains unclear. Dorsal root ganglia (DRG) house pseudounipolar afferent neurons responsible for signals such as temperature, proprioception and nociception. This study aimed to investigate the presence and function of telocytes in human DRG by investigating their transcriptional profile, location and ultrastructure. Sequencing data revealed CD34 and PDGFRA expressing cells comprise roughly 1.5-3% of DRG cells. Combined expression of CD34 and PDGFRA is a putative marker gene set for telocytes. Further analysis identified nine subclusters with enriched cluster-specific genes. KEGG and GO pathway analysis suggested vascular, immune and connective tissue associated putative telocyte subtypes. Over 3000 potential receptor-ligand interactions between sensory neurons and these CD34 and PDGFRA expressing putative telocytes were identified using a ligand-receptors interactome platform. Immunohisto-chemistry showed CD34+ telocytes in the endoneural space of DRGs, next to neuron-satellite complexes, in perivascular spaces and in the endoneural space between nerve fibre bundles, consistent with pathway analysis. Transmission electron microscopy (TEM) confirmed their location identifying characteristic elongated nucleus, long and thin telopods containing vesicles, surrounded by a basal lamina. This is the first study that provides gene expression analysis of telocytes in complex human tissue such as the DRG, highlighting functional differences based on tissue location with no significant ultrastructural variation.

Macular exudate in idiopathic intracranial hypertension affects outer retina and visual acuity

BackgroundOptical coherence tomography (OCT) is suggested as a potential tool for retinal biomarkers in idiopathic intracranial hypertension (IIH). We explored how macular exudate (ME) affects retinal structure in IIH and...

Could the thick of retinal nerve fiber layer be a potential measure of axonal loss in hearing loss?

Could the thick of retinal nerve fiber layer be a potential measure of axonal loss in hearing loss?

N-Check: nerve check to document chemotherapy-induced peripheral neuropathy (CIPN) in incurable cancer

Chemotherapy-induced polyneuropathy (CIPN) encompasses aspectrum of symptoms ranging from hypoesthesia with impaired gait, stance and fine motor skills to painful dysesthesia and allodynia and significantly impairs the quality of life of those affected. In the present pilot study, quantitative sensory testing (QST) was used to investigate CIPN as acommon adverse effect of cytostatic drugs in patients with incurable cancer. The QST is astandardized examination procedure that is not yet routinely used in cancer patients. It is used to examine thermal and mechanical perception and pain thresholds to record the subjectively experienced pain phenotype. In the N‑Check pilot project, the QST was used before and after tumor-specific, potentially CIPN-inducing treatment and the data collected was compared in apre-post analysis. In addition, the specific effects of CIPN on the health-related quality of life of patients treated primarily with apalliative intention were recorded using the Functional Assessment for Cancer Therapy-General (FACT-G) questionnaire. Overall, the patients showed significant heat hypoalgesia after chemotherapy as asign of damage to small nerve fibers. In addition, there were signs of deterioration of the quality of life. The feasibility of QST in patients with incurable cancer and palliative, neurotoxic chemotherapy was demonstrated in this pilot study.

Correction to “Automated immunohistochemistry of intra‐epidermal nerve fibres in skin biopsies: A proof‐of‐concept study”

Correction to “Automated immunohistochemistry of intra‐epidermal nerve fibres in skin biopsies: A proof‐of‐concept study”

Bioelectronic Medicines-A Novel Approach of Therapeutics in Current Epoch.

Bioelectronic medicines aim to diagnose and treat a wide range of illnesses and ailments, including cancer, rheumatoid arthritis, inflammatory bowel disease, obesity, diabetes, asthma, paralysis, blindness, bleeding, ischemia, organ transplantation, cardiovascular disease, and neurodegenerative diseases. The focus of bioelectronic medicine is on electrical signaling of the nervous system. Understanding the nervous system's regulatory roles and developing technologies that record, activate, or inhibit neural signaling to influence particular biological pathways. Bioelectronic medicine is an emerging therapeutic option with the interconnection between molecular medicine, neuroscience, and bioengineering. The creation of nerve stimulating devices that communicate with both the central and peripheral nervous systems has the potential to completely transform how we treat disorders. Although early clinical applications have been largely effective across entire nerves, the ultimate goal is to create implantable, miniature closed-loop systems that can precisely identify and modulate individual nerve fibers to treat a wide range of disorders. The data bases such as PubMed, and Clinicaltrial.gov.in were searched for scientific research, review and clinical trials on bioelectronic medicine. The field of bioelectronic medicine is trending at present. In recent years, researchers have extended the field's applications, undertaken promising clinical trials, and begun delivering therapies to patients, thus creating the groundwork for significant future advancements. Countries and organizations must collaborate across industries and regions to establish an atmosphere and guidelines that foster the advancement of the field and the fulfillment of its prospective advantages.

Measurement of the Tilt Angle of the Optic Disc Using Spectral-Domain Optical Coherence Tomography and Related Factors in Myopia.

This study presents a novel, three-dimensional method for measuring the tilt angle of the tilted optic disc (TOD) using spectral-domain optical coherence tomography (SD-OCT) and investigates the correlation between ocular-related parameters and TOD. We included the right eyes of 243 healthy young individuals, categorized by axial length. We measured the ovality index (OI) and dihedral angle (DA) using SD-OCT infrared ray fundus photographs and high-resolution cross-sectional images of the optic disc, respectively. The relationships between OI, DA, and ocular-related parameters were analyzed. Eyes in the longer axial length group exhibited a lower OI and a higher DA, along with thinner nasal and inferonasal circumpapillary retinal nerve fiber layer (cpRNFL) and thicker temporal and superotemporal cpRNFL. There was a significant relationship between DA and cpRNFL thickness. The new method utilizing DA to measure the tilt angle of TOD demonstrated high repeatability. We propose a novel, three-dimensional, and quantitative method for evaluating the tilt degree of TOD. A higher degree of myopia indicated a greater tilt angle of the TOD, and a greater TOD suggested additional changes in cpRNFL thickness. These findings should be considered when interpreting increased susceptibility and early assessment of glaucoma in myopia. DA could serve as a superior indicator for describing TOD morphology during eyeball elongation and evaluating its impact on related parameters of the optic disc and peripapillary structures in the myopic population.

The Effect of Mesenchymal Stem Cell Administration on the Expression of Nuclear Factor Kappa Beta, Neural Growth Factor Expression, and Prostaglandin E2 Concentration as Determinants of Pain in a Mouse Model of Endometriosis

Endometriosis is a significant reproductive health issue with pain being the primaru symptom. The complex pain in endometriosis involves the activation of macrophages, inflammatory activators such as NF-kB, neural growth factors (NGF), cytokines, adhesive molecules (ICAM-1), and mediators (PGE2) which they are stimulate sensory nerve fibers and produce nociceptive signals. This study is aim for investigate the effect of Mesenchymal Stem Cell (MSC) administration on the expression of NF-kB, NGF, and PGE2 concentration in a mouse model of endometriosis. Thirty-three mices were randomly divided into 3 groups consist non-endometriosis (P0), endometriosis without treatment (P1), and endometriosis with MSC administration (P2). The results showed MSC administration significantly reduced the expression of NF-kB by found scoring 2 groups (P1: 6.96 ± 0.13 and P2: 4.446 ± 0.228) and NGF (P1: 7.118 ± 0.629 and P2: 4.927 ± 1.187) also PGE2 (P1:1005.862 ± 176.656 and P2: 891.218 ± 54.031. In onclusion, this study demonstrates that MSC administration can able reduce the expression of NF-kB and NGF, but not to PGE2. The suggestion we can said is the MSC have potential therapeutic value in managing endometriosis-asssosciated pain by modulating inflammatory and neurotrophic factors. HIGHLIGHTS Pain in endometriosis, which is driven by inflammatory factors like NF-kB, NGF, cytokines, and PGE2, stimulating sensory nerve fibers and producing nociceptive signals. Investigate the effects of mesenchymal stem cell (MSC) administration on the expression of NF-kB, NGF, and PGE2 in a mouse model of endometriosis. Mesenchymal stem cell (MSC) administration was shown to reduce the expression of key inflammatory and neurotrophic factors—NF-kB and NGF—in a mouse model of endometriosis. Limited effect on reducing PGE2 concentration. These findings suggest that MSCs may have therapeutic potential for managing pain associated with endometriosis by modulating inflammatory and neurotrophic pathways. GRAPHICAL ABSTRACT

Progressive Thickening of Retinal Nerve Fiber and Ganglion Cell Complex Layers Following SDM Laser Vision Protection Therapy in Open-Angle Glaucoma.

This work aims to determine the effect on nerve fiber layer (NFL) and ganglion cell complex (GCC) thickness trends in eyes with open-angle glaucoma (OAG) treated with Vision Protection Therapy™ (VPT). A retrospective analysis of spectral-domain optical coherence tomography (OCT) measured NFL and GCC thickness trends was performed, excluding eyes with poor-quality scans and principal diagnoses other than OAG. This study compares eyes with OAG managed conventionally with IOP control alone (controls) to eyes managed with the addition of VPT (VPT eyes). The direction (+ or -) and magnitude (microns/year) of the OCT trends were the study endpoints. Seventy-eight control eyes of 40 patients and 61 VPT-treated eyes of 39 patients were included in the study. Positive NFL trends were noted in 5% of control eyes vs. 71% of VPT eyes (p < 0.0001). Positive GCC trends were noted in 8% of control eyes vs. 43% of VPT eyes (p < 0.0001). Mean NFL trends (µm/year) were - 0.692 for controls vs. 0.347 for VPT (p < 0.0001). Mean GCC trends (µm/year) were - 0.554 for controls vs. - 0.148 for VPT (p = 0.0175). The addition of VPT to the conventional management of OAG resulted in highly significant improvements in NFL and GCC trends, indicating a reversal of key indicators of glaucoma severity and progression.

Retinal and Corneal OCT Results of Patients Hospitalized and Treated in the Acute Phase of COVID-19.

Objective: This study aimed to assess changes in the morphology of the retina and cornea in patients treated and hospitalized during the acute active phase of SARS-CoV-2 infection. Methods: A total of 24 patients with symptomatic early COVID-19 disease and 38 healthy participants from a control group were enrolled in our study. Among them, 20 received oxygen therapy at flow rates ranging from 1-10 L, while four received high-flow intranasal oxygen therapy (HFNOT). Some patients were treated with other types of therapy, such as Remdesivir, COVID-19 convalescent plasma therapy, or Tocilizumab. In the study, we focused on the analysis of optical coherence tomography (OCT) images of the cornea and retina including corneal thickness, central retinal thickness, retinal nerve fiber layer (RNFL), and optic disc parameters. The measurements were acquired using Spectral-domain OCT REVO FC 130. Results: The analysis did not show significant changes between the examined ophthalmological parameters before and after therapy. Furthermore, there were no detected significant differences between the tested parameters of the retina and cornea in COVID-19-positive patients compared to the control group. Conclusions: No ophthalmological manifestations of COVID-19 disease were observed during the study. Taking into account the results of other publications, the lack of an unambiguous position on this topic requires further research.

A study of PGP 9.5 immunohistochemical labeling on formalin-fixed paraffin embedded tissues for epidermal nerve fiber density testing

ABSTRACT There have been several methods established for immunohistochemical labeling of the PGP 9.5 antigen in human tissue for the assessment of epidermal nerve fiber density, none of which uses neutral-buffered formalin as the preferred fixative for paraffin-embedded tissue. The literature maintains that formalin-fixed paraffin embedded tissues are unable to be used for this purpose and that other fixatives must be used due to the cross-linkages caused by formalin fixation. This study was undertaken to develop a standardized method for the use of formalin-fixed paraffin embedded tissues for immunohistochemical labeling and assessment of epidermal nerve fiber density. Formalin-fixed paraffin embedded tissues from the punch biopsies of patients suspected to have small fiber neuropathy were prepared for immunohistochemical labeling using heat-induced epitope retrieval for one hour at 92°C. The tissues were then stained with a polyclonal rabbit anti-human PGP 9.5 primary antibody. The resulting stains were then evaluated by a licensed pathologist who counted the number of epidermal nerve fibers stained and recorded the epidermal length in millimeters. Human foreskin was used as the tissue control in these studies. Satisfactory immunohistochemical labeling of epidermal nerve fibers was achieved from formalin-fixed paraffin embedded tissues through the use of heat-induced epitope retrieval. The authors of this paper have concluded that formalin-fixed paraffin embedded tissues may be used to achieve satisfactory immunohistochemical labeling for the assessment of epidermal nerve fiber density.

Autoantigens of Small Nerve Fibers and Human Coronavirus Antigens: Is There a Possibility for Molecular Mimicry?

In post-COVID-19 syndrome, clinical presentation of the nerve fiber dysfunction plays an important role. The possibility of autoantigen cross-mimicry of human coronaviruses and the peripheral nervous system needs to be investigated. The bioinformatic analysis was applied to search for possible common protein sequences located in the immunoreactive epitopes. Among the autoantigens of the human nervous system, fibroblast growth factor receptor protein 3, myelin protein P0, myelin protein P2, sodium channel protein type 9, alpha protein subunit, plexin-D1 protein and ubiquitin-carboxyl-terminal hydrolase protein of the L1 isoenzyme were selected. The original "Alignmentaj" analytical program was created. The UniProt database, Protein Data Bank, and AlphaFold databases were used. The analysis of protein sequence similarities of spike glycoproteins in human coronaviruses revealed common pentapeptides of the MERS-CoV-2 virus with the fibroblast growth factor receptor 3 and myelin protein P2. Among seasonal coronaviruses, common peptide sequences were identified in HCoV-HKU-1 virus with sodium channel protein type 9 subunit alpha and Plexin-D1, HCoV-OC43 with Plexin-D1, as well as HCoV-NL63 with Plexin-D1 and Ubiquitin carboxyl-terminal hydrolase isozyme L1. Some shared peptides belong to immunoreactive epitopes. The most important targets for the molecular similarities are the sodium channel subunits and fibroblast growth factor receptor 3, both for seasonal and highly pathogenic coronaviruses. The data obtained make it possible to identify new potential targets for the development of autoimmune reactions that may occur against the background of the infections with highly pathogenic as well as seasonal coronaviruses.

Lamina Cribrosa Microstructure in Nonhuman Primates With Naturally Occurring Peripapillary Retinal Nerve Fiber Layer Thinning.

The lamina cribrosa (LC) is hypothesized to be the site of initial axonal damage in glaucoma with the circumpapillary retinal nerve fiber layer thickness (RNFL-T) widely used as a standard metric for quantifying the glaucomatous damage. The purpose of this study was to determine in vivo, 3-dimensional (3D) differences in the microstructure of the LC in eyes of nonhuman primates (NHPs) with naturally occurring glaucoma. Spectral-domain optical coherence tomography (OCT) scans (Leica, Chicago, IL, USA) of the optic nerve head were acquired from a colony of 50 adult rhesus monkeys suspected of having high prevalence of glaucoma. The RNFL-T was analyzed globally and in quadrants using a semi-automated segmentation software. From a set of 100 eyes, 18 eyes with the thinnest global RNFL-T were selected as the study group and 18 eyes with RNFL-T values around the 50th percentile were used as controls. A previously described automated segmentation algorithm was used for LC microstructure analysis. Parameters included beam thickness, pore diameter and their ratio (beam-to-pore ratio [BPR]), pore area and shape parameters, beam and pore volume, and connective tissue volume fraction (CTVF; beam volume/total volume). The LC microstructure was analyzed globally and in the following volumetric sectors: quadrants, central and peripheral lamina, and three depth slabs (anterior, middle, and posterior). Although no significant difference was detected between groups for age, weight, or disc size, the study group had significantly thinner RNFL than the control group (P < 0.01). The study group had significantly smaller global and sectoral pore diameter and larger BPR compared with the control group. Across eyes, the global RNFL-T was associated positively with pore diameter globally. BPR and CTVF were significantly and negatively associated with the corresponding RNFL-T in the superior quadrant. Global and sectoral microstructural differences were detected when comparing thin and normal RNFL-T eyes. Whether these LC differences are the cause of RNFL damage or the result of remodeling of the LC requires further investigation. Our findings indicate structural alterations in the LC of NHP exhibiting natural thinning of the RNFL, a common characteristic of glaucomatous damage.

Retinal nerve fiber layer defects and chronic kidney disease: the Kailuan Eye Study.

To investigate whether retinal nerve fiber layer defects (RNFLDs) is a potential risk factor for chronic kidney disease (CKD) in Chinese adults. The Kailuan Eye Study was a population-based study that included 14 440 participants. All participants underwent detailed assessments, RNFLDs were diagnosed using color fundus photographs. Overall, 12 507 participants [8533 males (68.23%)] had complete systemic examination data and at least one evaluable fundus photograph. RNFLDs were found in 621 participants [5.0%; 95% confidence interval (CI): 4.6%-5.34%], and 70 cases of multiple RNFLDs were found (11.27%). After adjusting multiple factors, RNFLDs was significantly associated with CKD severity, the ORs of CKD stage 3, stage 4 and stage 5 were 1.698, 4.167, and 9.512, respectively. Multiple RNFLDs were also associated with CKD severity after adjusting multiple factors, the ORs of CKD stage 3 and stage 5 were 4.465 and 11.833 respectively. Furthermore, 2294 participants had CKD (18.34%, 95%CI: 17.68%-18.99%). After adjusting for other factors, CKD presence was significantly correlated with the presence of RNFLDs. The strongest risk factors for RNFLDs are CKD and hypertension. Conversely, RNFLDs can be an ocular feature in patients with CKD. Fundoscopy can help detect systemic diseases, and assessment for RNFLDs should be considered in CKD patients.

Retinal ischemia-reperfusion injury and pretreatment with Lycium barbarum glycopeptide.

To investigate the antioxidant protective effect of Lycium barbarum glycopeptide (LbGP) pretreatment on retinal ischemia-reperfusion (I/R) injury (RIRI) in rats. RIRI was induced in Sprague Dawley rats through anterior chamber perfusion, and pretreatment involved administering LbGP via gavage for 7d. After 24h of reperfusion, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine (CREA) levels, retinal structure, expression of Caspase-3 and Caspase-8, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) in the retina were measured. The pretreatment with LbGP effectively protected the retina and retinal tissue from edema and inflammation in the ganglion cell layer (GCL) and nerve fiber layer (NFL) of rats subjected to RIRI, as shown by light microscopy and optical coherence tomography (OCT). Serum AST was higher in the model group than in the blank group (P=0.042), but no difference was found in ALT, AST, and CREA across the LbGP groups and model group. Caspase-3 expression was higher in the model group than in the blank group (P=0.006), but no difference was found among LbGP groups and the model group. Caspase-8 expression was higher in the model group than in the blank group (P=0.000), and lower in the 400 mg/kg LbGP group than in the model group (P=0.016). SOD activity was lower in the model group than in the blank group (P=0.001), and the decrease was slower in the 400 mg/kg LbGP group than in the model group (P=0.003). MDA content was higher in the model group than in the blank group (P=0.001), and lower in the 400 mg/kg LbGP group than in the model group (P=0.016). The pretreatment with LbGP did not result in any observed liver or renal toxicity in the model. LbGP pretreatment exhibits dose-dependent anti-inflammatory, and antioxidative effects by reducing Caspase-8 expression, preventing declines of SOD activity, and decreasing MDA content in the RIRI rat model.

Corneal nerve changes by anti-glaucoma medications examined by in vivo confocal microscopy.

To evaluate the effects of antiglaucoma eye drops on corneal nerves by in vivo confocal microscopy (IVCM). This study comprised 79 patients diagnosed with glaucoma and 16 healthy control individuals. Among the glaucoma patients, 54 were treated with medication, while 25 remained untreated. Central corneal images were evaluated by IVCM, and then ACCMetrics was used to calculate the following parameters: corneal nerve fiber density (CNFD), branch density (CNBD), fiber length (CNFL), total branch density (CTBD), fiber area (CNFA), fiber width (CNFW), and fractal dimension (CNFrD). The correlation between IVCM parameters and drugs was evaluated using non-parametric measurements of Spearman's rank correlation coefficient. The CNFD was reduced in glaucoma groups compared to healthy subjects (P<0.01). Patients using anti-glaucoma medications exhibited poorer confocal parameters compared to untreated patients. As the number of medications and usage count increased, CNFD, CNBD, CNFL, CTBD, CNFA, and CNFrD experienced a decline, while CNFW increased (all P<0.01). For the brinzolamide-therapy group, there was a significant decrease in CNFD and CNFL compared to the other monotherapy groups (P<0.001). In the absence of medication, CNFD in males was lower than that in females (P<0.05). Among patients under medication therapy, CNFD remained consistent between males and females. Antiglaucoma eye drops affect the microstructure of corneal nerves. IVCM and ACCMetrics are useful tools that could be used to evaluate the corneal nerve changes.

Characterization of Novel SARM1 Inhibitors for the Treatment of Chemotherapy-Induced Peripheral Neuropathy.

Sterile α and Toll/IL-1 receptor motif-containing 1 (SARM1) is a central regulator of programmed axon death and a crucial nicotinamide adenine dinucleotide (NAD+) hydrolase (NADase) in mammalian tissues, hydrolyzing NAD+ and playing an important role in cellular NAD+ recycling. Abnormal SARM1 expression is linked to axon degeneration, which causes disability and disease progression in many neurodegenerative disorders of the peripheral and central nervous systems. In this study, we use PC6 assay of hydrolase activity, DRG axon regeneration and CIPN model to screen for potent SARM1 Inhibitors. Two novel SARM1 inhibitors (compound 174 and 331P1) are charcterized for its high potency for SARM1 NADase. In a chemotherapy-induced peripheral neuropathy (CIPN) myopathy model, compound 331P1 treatment prevented the decline in neurofilament light chain (NfL) levels caused by axonal injury in a dose-dependent manner, associated with elevated intraepidermal nerve fiber (IENF) intensity in mouse foot paw tissue, suggesting its functionality in reversing axon degeneration. The newly designed SARM1 inhibitor 331P1 is a promising candidate due to its excellent in vivo efficacy, favorable CYP inhibition properties, and attractive safety profiles. The 331P1 compound possesses the potential to be developed as a novel neuroprotective therapy that can prevent or halt the neurodegenerative process in CIPN.