Search Results (409)

We previously reported ocular phenotypes of 1-year-old 129S1/SvlmJ lysyl oxidase-like 1 null (Loxl1^−/−) mice. Here we sought to characterize age-dependent changes in C57BL/6J Loxl1^−/− mice in a longitudinal fashion. Retinal ganglion cell (RGC) function was assessed by electroretinography (ERG), and optic nerves were evaluated by histological analysis. Ocular biometric measurements were obtained by optical coherence tomography (OCT). We detected reduced RGC function, revealed by decreased amplitude and increased latency of ERG positive scotopic threshold responses (pSTRs) in Loxl1^−/− mice compared to age-matched wt mice. In addition, there is significant inter-eye asymmetry of RGC function, as well as age-related RGC function loss observed only in Loxl1^−/− mice. Histologically, we observed enlarged optic nerve areas in Loxl1^−/− mice compared to wt mice. Significant ocular biometric differences between two groups were detected, most notably, age-related axial elongation of the globe, accompanied by deepening of anterior chamber depth (ACD). Though eyes elongate with age in both groups, this is more pronounced in Loxl1^−/− mice, and the elongation of the globe correlated with decreased RGC function. The correlation of age-related reduction in RGC function with globe axial elongation may have implications for the association of axial myopia with glaucoma and aging in humans. Full article

This review examines how diabetes affects the ganglion cells of the retina, including the axons that make up the optic nerve. Links between established changes in the morphology of retinal ganglion cells (RGCs) and vision loss, as well as other functions, such as the pupillary light reflex, are considered. RGC morphology and function are significantly altered in both animal models and humans with diabetes. Diabetes affects all parts of the RGC, including the dendrites, the cell body, the axons making up the nerve fiber layer, and the optic nerve. Subtypes of RGCs appear to be affected differently by diabetes, and the morphology and electrophysiological output are more significantly affected in ON-RGCs than in OFF cells, which may explain part of the mechanism underlying the widely documented diabetes-induced reduction in contrast sensitivity. Furthermore, the morphology of the specialized light-sensitive melanopsin-containing RGCs also appears to be affected by diabetes, which may explain deficits in circadian rhythm and the pupillary light reflex. Potential therapeutic approaches aimed at protecting RGCs in diabetes are also discussed. Overall, strong evidence supports the conclusion that diabetes impacts the form and function of RGCs and their axons within the optic nerve, resulting in deficient regulation of circadian rhythms and the pupillary light reflex, in addition to vision. Full article

Background: Glaucoma is a progressive optic neuropathy marked by retinal ganglion cells (RGCs), apoptosis, vascular insufficiency, oxidative stress, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. While intraocular pressure (IOP) reduction remains the primary intervention, many patients continue to lose vision despite adequate pressure control. Emerging neuroprotective agents—citicoline, coenzyme Q10 (CoQ10), pyruvate, nicotinamide, pyrroloquinoline quinone (PQQ), homotaurine, berberine, and gamma-aminobutyric acid (GABA)—target complementary pathogenic pathways in experimental and clinical settings. Methods: This literature review synthesizes current evidence on glaucoma neuroprotection, specifically drawing on the most relevant and recent studies identified via PubMed. Results: Citicoline enhances phospholipid synthesis, stabilizes mitochondrial membranes, modulates neurotransmitters, and improves electrophysiological and visual field outcomes. CoQ10 preserves mitochondrial bioenergetics, scavenges reactive oxygen species, and mitigates glutamate-induced excitotoxicity. Pyruvate supports energy metabolism, scavenges reactive oxygen species, and restores metabolic transporter expression. Nicotinamide and its precursor nicotinamide riboside boost NAD⁺ levels, protect against early mitochondrial dysfunction, and enhance photopic negative response amplitudes. PQQ reduces systemic inflammation and enhances mitochondrial metabolites, while homotaurine modulates GABAergic signaling and inhibits β-amyloid aggregation. Berberine attenuates excitotoxicity, inflammation, and apoptosis via the P2X7 and GABA-PKC-α pathways. Preclinical models demonstrate synergy when agents are combined to address multiple targets. Clinical trials of fixed-dose combinations—such as citicoline + CoQ10 ± vitamin B3, citicoline + homotaurine ± vitamin E or PQQ, and nicotinamide + pyruvate—show additive improvements in RGCs’ electrophysiology, visual function, contrast sensitivity, and quality of life without altering IOP. Conclusions: A multi-targeted approach is suitable for glaucoma’s complex neurobiology and may slow progression more effectively than monotherapies. Ongoing randomized controlled trials are essential to establish optimal compound ratios, dosages, long-term safety, and structural outcomes. However, current evidence remains limited by small sample sizes, heterogeneous study designs, and a lack of long-term real-world data. Integrating combination neuroprotection into standard care holds promise for preserving vision and reducing the global burden of irreversible glaucoma-related blindness. Full article

Glaucoma is traditionally classified as an ocular disease characterized by progressive retinal ganglion cell (RGC) loss and optic nerve damage. However, emerging evidence suggests that its pathophysiology may extend beyond the eye, involving trans-synaptic neurodegeneration along the visual pathway and structural changes within central brain regions, including the lateral geniculate nucleus and visual cortex. In this narrative review, we have used the phrase ‘brain involvement’ to underscore central changes that accompany or follow retinal ganglion cell loss; we have not intended to redefine glaucoma as a primary cerebral disorder. Neuroimaging studies and neurocognitive assessments in adult glaucoma patients, primarily older individuals with primary open-angle glaucoma reveal that glaucoma patients may exhibit alterations in brain connectivity and cortical thinning, aligning it more closely with neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. This evolving neurocentric perspective raises important questions regarding shared mechanisms—such as mitochondrial dysfunction, chronic inflammation, and impaired axonal transport—that may link glaucomatous optic neuropathy to central nervous system (CNS) pathology. These insights open promising therapeutic avenues, including the repurposing of neuroprotective and neuroregenerative agents, targeting not only intraocular pressure (IOP) but also broader CNS pathways. Furthermore, neuroimaging biomarkers and brain-targeted interventions may play a future role in diagnosis, prognosis, and individualized treatment. This review synthesizes current evidence supporting glaucoma as a CNS disease, explores the mechanistic overlap with neurodegeneration, and discusses the potential clinical implications of glaucoma within a neuro-ophthalmologic paradigm. Full article

Background: Considering the lack of studies regarding the localized evaluation of the macular inner retina in multiple sclerosis patients without optic neuritis (MSnoON eyes), we investigated the structure and function of retinal ganglion cells (RGCs) located in different macular areas. Methods: In 24 MSnoON patients (mean age: 45.22 ± 5.57 years; 14 females and 10 males; mean MS disease duration: 11.07 ± 5.88 years) and in 30 age-similar (mean age: 45.09 ± 5.08 years) control subjects, complete ophthalmological examination, optical coherence tomography (OCT) and multifocal photopic negative response (mfPhNR) were performed. The ganglion cell layer thickness (GCL+-T) via OCT and the response amplitude density (RAD) through mfPhNR were measured from localized macular regions, including rings and Early Treatment of Diabetic Retinopathy Study (ETDRS) sectors. Results: When comparing MSnoON data from all tested areas with respect to the controls, macular GCL+-T and mfPhNR RAD mean values were found to be significantly (ANOVA, p < 0.01) reduced. In the MSonON group, considering both rings and sectors, the GCL+-T values were significantly and linearly correlated (Pearson’s test, p < 0.01) to the mfPhNR RAD values. Conclusions: In MS, even in the absence of optic neuritis, potential primary morpho-functional involvement of the inner macular elements can occur. This impairment widely involves all macular areas and sectors. Full article

Glaucoma is recognized as a chronic optic neuropathy marked by progressive optic nerve degeneration, loss of retinal ganglion cells (RGCs, the neurons responsible for transmitting visual information from the eye to the brain), disruptions in optic disc blood supply, and changes in glial cell activation. It ranks as the second most prevalent cause of irreversible visual impairment worldwide and is a resultant of increased intraocular pressure (IOP). Addressing this condition proves complex due to the inherent hindrances posed by ocular barriers, which curtail the entry of drugs into the eye. Diverse carriers such as inorganic nanoparticles, polymeric nanocarriers, hydrogels, and contact lens-based systems with distinct physical and chemical attributes are being studied for drug delivery. They have shown enhanced ocular drug bioavailability through higher penetration across ocular tissues, prolonged retention in the precorneal space, sustained drug release, and targeted delivery to specific tissues. These ingenious delivery systems can be deployed through various administration routes—intravitreal or periocular injections or systemic administration—enabling the drugs to reach affected areas, aiding in the regeneration of compromised optical nerves. This review presents a comprehensive exploration of contemporary strides in ocular delivery formulations pertaining to glaucoma. This encompasses an examination of various nanocarrier typologies, delivery routes, in vitro and in vivo effectiveness, clinical applicability, and a forward-looking perspective into potential future developments. Full article

Background/Objectives: The aim of this study was to evaluate the relationship between foveal avascular zone (FAZ) enlargement, retinal ganglion cell (RGC) dysfunction, and structural retinal measurements in glaucoma suspects (GS), using pattern electroretinogram (PERG) and optical coherence tomography angiography (OCTA) parameters. Methods: Thirty-one eyes (20 subjects) of GS status underwent comprehensive ophthalmologic evaluation including steady-state PERG, optical coherence tomography (OCT), and OCTA. FAZ area was measured using ImageJ software (version 1.54p), and PERG parameters (Magnitude, MagnitudeD, and MagnitudeD/Magnitude ratio) were analyzed. Partial correlation analyses were performed to assess associations between FAZ area, PERG parameters, and structural metrics including retinal nerve fiber layer (RNFL), ganglion cell layer–inner plexiform layer (GCL + IPL), and macular thickness. Results: After controlling for age, sex, central corneal thickness (CCT), intraocular pressure (IOP), and spherical equivalent, partial correlation analysis showed that FAZ area was significantly associated with both lower Magnitude (r < −0.503, p < 0.05) and MagnitudeD (r < −0.507, p < 0.05) values. PERG parameters were significantly correlated with superior and average RNFL thickness, as well as superior and superior temporal GCL + IPL thickness. FAZ area was significantly associated with multiple GCL + IPL and macular thickness sectors, but not with RNFL thickness. Conclusions: FAZ enlargement is significantly associated with RGC dysfunction and inner retinal layer thinning in GS. Full article

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed the management of type 2 diabetes mellitus and obesity. However, their sustained effect on delaying gastric emptying raises new challenges in gastrointestinal endoscopy performed under sedation. This narrative review aims to summarize current evidence on the impact of GLP-1 RAs on gastric motility and to propose clinical strategies to mitigate associated procedural risks. Methods: A narrative review was conducted integrating findings from scintigraphy, capsule endoscopy, gastric ultrasound, and existing clinical guidelines. Emphasis was placed on studies reporting residual gastric content (RGC), anesthetic safety outcomes, and procedural feasibility in patients undergoing endoscopy while treated with GLP-1 RAs. Results: GLP-1 RAs significantly increase the prevalence of clinically relevant RGC, despite prolonged fasting, with potential implications for airway protection and sedation safety. Although the risk of pulmonary aspiration remains low (≤0.15%), procedural delays, modifications, or cancellations can occur in up to 30% of cases without adapted protocols. Several professional societies (AGA, ASGE, AASLD) advocate for individualized management based on procedure type, symptomatology, treatment phase, and point-of-care gastric ultrasound (POCUS), in contrast to the systematic discontinuation recommended by the ASA. Conclusions: Effective management requires personalized fasting protocols, risk-based stratification, tailored anesthetic approaches, and interprofessional coordination. We propose a clinical decision algorithm and highlight the need for training in gastrointestinal pharmacology, POCUS, and airway management for endoscopists. Future priorities include prospective validation of clinical algorithms, safety outcome studies, and the development of intersocietal consensus guidelines. Full article

Objective: To investigate the neuroprotective effects of a Rho-associated kinase (ROCK) inhibitor on retinal ganglion cells (RGCs) in vitro and in vivo. Methods: For in vivo studies, a unilateral optic nerve crush mouse model was established. Then, 100 mM Y-27632 (a ROCK inhibitor) or saline was applied to the experimental eyes once a day for 14 days. The effects of the ROCK inhibitor were evaluated by counting the surviving RGCs in the enucleated flat retina tissues and measuring the inner retinal thickness using optical coherence tomography (OCT), the amplitude of the electroretinogram (ERG), and the change in intraocular pressure (IOP). For the in vitro study, RGCs were isolated from five-day-old mice using a modified immunopanning method with magnetic beads. The isolated RGCs were incubated for 72 h with various concentrations of Y-27632, after which TUNEL assays were performed to determine the number of surviving RGCs. Results: Y-27632 has neuroprotective effects, as it significantly increased the number of surviving RGCs by approximately 6.3%. OCT and ERG data also revealed that Y-27632 induced neuroprotective effects in vivo; furthermore, Y-27632 reduced IOP by approximately 18.3%. The in vitro study revealed the dose-dependent neuroprotective effects of Y-27632, with the highest dose of Y-27632 (1000 nM) increasing the RGC survival rate after 72 h of incubation compared with that of the control. Conclusions: The ROCK inhibitor Y-27632 may exert some neuroprotective effects on RGCs when it is used as an eye drop through an IOP-independent mechanism. Full article

Azole resistance in dermatophytes, particularly Trichophyton indotineae, has become a growing global concern. Current antifungal susceptibility testing protocols (EUCAST, CLSI) have limitations in reproducibility and sensitivity. This study aimed to evaluate how medium composition, incubation temperature, and spore concentration influence itraconazole susceptibility testing across various dermatophyte species. Thirty-eight clinical isolates representing Trichophyton, Microsporum, and Epidermophyton species were tested using a microplate laser nephelometry system (MLN). IC₅₀ values for itraconazole were determined in three different media (Sabouraud glucose (SG), RPMI-based (RG), and RG supplemented with casein (RGC)) at 28 °C and 34 °C. Effects of spore concentration on growth dynamics and lag phase were also analyzed. SG medium provided clear phenotypic separation between resistant and sensitive isolates. In contrast, RG and RGC showed overlapping IC₅₀ values. Lower spore concentrations revealed underlying growth differences, which were masked at higher inoculum levels. Temperature and media composition significantly affected IC₅₀ outcomes. Genotypic analysis confirmed resistance-associated Erg11B point mutations and genomic amplifications in T. indotineae, particularly in combination with Erg1 mutations, forming distinct subpopulations. SG medium combined with reduced spore concentrations offered improved differentiation of resistant versus sensitive strains. These findings support the development of more accurate susceptibility testing protocols and highlight the need to establish species-specific ECOFF values for dermatophytes. Full article

This review investigates the role of building windows in supporting occupant well-being through access to natural views and daylight. This review synthesizes recent interdisciplinary research from environmental psychology, building science, and human physiology to examine how windows impact cognitive performance, psychological restoration, and circadian health. Drawing on 304 peer-reviewed studies from 2000 to 2024, the review identifies two core pathways: visual effects—related to daylight availability, glare control, and view quality—and non-visual effects—linked to circadian entrainment and neuroendocrine regulation via ipRGCs. These effects interact yet compete, necessitating a multi-objective optimization approach. This paper evaluates commonly used metrics for visual comfort, circadian-effective lighting, and view quality and discusses their integration in design frameworks. The review also highlights the potential of adaptive facade technologies and artificial window systems to balance human-centered lighting goals with energy efficiency. A research roadmap is proposed to support future integrative design strategies that optimize both visual and non-visual outcomes in diverse architectural contexts. Full article

Non-arteritic anterior ischemic optic neuropathy (NAION) leads to retinal ganglion cell (RGC) loss and visual impairment, with no effective treatment. This study investigated the neuroprotective effect of 670 nm photobiomodulation (PBM) in a rat NAION model (rNAION). Wistar rats received 670 nm light exposure (10-min, 3000 lux) twice daily for 3 days after rAION injury, followed by 4 days of light treatment once a day. This study evaluated the neuroprotective effects of 670 nm light in an rNAION model. Rats received 670 nm light therapy (10 min/day, 3000 lux) for seven days post-injury. Treatment improved visual function (a 3.36-fold increase in FVEP amplitude), enhanced RGC survival (1.55-fold), and reduced apoptosis (a 15.86-fold reduction in TUNEL-positive cells). Inflammatory cytokines and ED1+ macrophage infiltration were significantly decreased. Oxidative stress was attenuated, with increased ATP, Nrf2, and PGC-1α levels and improved mitochondrial dynamics. These findings support 670 nm light as a potential therapy for NAION. Full article

Background/Objectives: The early detection of retinal ganglion cell (RGC) dysfunction is critical for timely intervention in glaucoma suspects (GSs). The combined structure–function index (CSFI), which uses visual field and optical coherence tomography (OCT) data to estimate RGC counts, may be of limited utility in GSs. This study evaluates whether steady-state pattern electroretinogram (ssPERG)-derived estimates better predict early structural changes in GSs. Methods: Fifty eyes from 25 glaucoma suspects underwent ssPERG and spectral-domain OCT. Estimated RGC counts (eRGCC) were calculated using three parameters: ssPERG-Magnitude (eRGCC_Mag), ssPERG-MagnitudeD (eRGCC_MagD), and CSFI (eRGCC_CSFI). Linear regression and multivariable models were used to assess each model’s ability to predict the average retinal nerve fiber layer thickness (AvRNFLT), average ganglion cell layer–inner plexiform layer thickness (AvGCL-IPLT), and rim area. Results: eRGCC_Mag and eRGCC_MagD were significantly correlated with eRGCC_CSFI. Both PERG-derived models outperformed eRGCC_CSFI in predicting AvRNFLT and AvGCL-IPLT, with eRGCC_MagD showing the strongest association with AvGCL-IPLT. Conversely, the rim area was best predicted by eRGCC_Mag and eRGCC_CSFI. These findings support a linear relationship between ssPERG parameters and early RGC structural changes, while the logarithmic nature of visual field loss may limit eRGCC_CSFI’s predictive accuracy in GSs. Conclusions: ssPERG-derived estimates, particularly eRGCC_MagD, better predict early structural changes in GSs than eRGCC_CSFI. eRGCC_MagD’s superior performance in predicting GCL-IPLT highlights its potential utility as an early biomarker of glaucomatous damage. ssPERG-based models offer a simpler and more sensitive tool for early glaucoma risk stratification, and may provide a clinical benchmark for tracking recoverable RGC dysfunction and treatment response. Full article

Glial cells, once considered mere support for neurons, have emerged as key players in brain function across vertebrates. The historical study of glia dates to the 19th century with the identification of ependymal cells and astrocytes, followed by the discovery of oligodendrocytes and microglia. While neurocentric perspectives overlooked glial functions, recent research highlights their essential roles in neurodevelopment, synapse regulation, brain homeostasis, and neuroimmune responses. In teleost fish, a group comprising over 32,000 species, glial cells exhibit unique properties compared to their mammalian counterparts. Thus, the aim of this review is synthesizing the current literature on fish glial cells, emphasizing their evolutionary significance, diversity, and potential as models for understanding vertebrate neurobiology. Microglia originate from both yolk sac cells and hematopoietic stem cells, forming distinct populations with specialized functions in the adult brain. Neural stem cells, including radial glial cells (RGCs) and neuroepithelial cells, remain active throughout life, supporting continuous neuro- and gliogenesis, a phenomenon far more extensive than in mammals. Ependymocytes line brain ventricles and show structural variability, with some resembling quiescent progenitor cells. Astrocytes are largely absent in most fish species. However, zebrafish exhibit astrocyte-like glial cells which show some structural and functional features in common with mammalian astrocytes. Oligodendrocytes share conserved mechanisms with mammals in myelination and axon insulation. Full article

Background: An acute angle-closure attack (AAC) is an ocular emergency that results from a rapid increase in intraocular pressure (IOP). Sustained IOP elevation induces severe degeneration of retinal ganglion cells (RGCs) without treatment. Overactivated microglia, key participants in innate immune responses, have critical roles in the pathogenesis of IOP-induced RGC death, although precise mechanisms remain unclear. In the present study, we used a rat ex vivo acute glaucoma model to investigate the role of microglial signaling in RGC death and examined whether pharmacological depletion of microglia using a CSF-1R inhibitor, PLX5622, exerts neuroprotection against pressure-induced retinal injury. Methods: Ex vivo rat retinas were exposed to hydrostatic pressure (10 mmHg or 75 mmHg) for 24 h. Pressure-dependent changes in retinal microglia and RGCs were detected by immunofluorescence. Morphological changes in the retina and RGC apoptosis were examined using light microscopy and TUNEL staining, respectively. The expression of NLRP3, active caspase-1, pro IL-1β, and IL-1β were examined using Western blotting. Effects of PLX5622, an agent that depletes microglia, were examined in morphology, apoptosis, and protein expression assays, while TAK-242, a TLR4 inhibitor, was examined against protein expression. Results: Pressure loading at 75 mmHg markedly increased activated microglia and apoptotic RGCs in the isolated retinas. Western blotting revealed increases in expression of NLRP3, active caspase-1, pro IL-1β, and IL-1β at 75 mmHg compared to 10 mmHg. Inhibition of pressure-induced increases in NLRP3 by TAK-242 indicates that pressure elevation induces RGC death via activation of the TLR4–NLRP3 inflammasome cascade. PLX5622 depleted microglia at 75 mmHg and significantly decreased expression of NLRP3, active caspase-1, pro IL-1β, and IL-1β at 75 mmHg, resulting in preservation of RGCs. Conclusions: These results indicate that pressure elevation induces proliferation of inflammatory microglia and promotes IL-1β production via activation of the TLR4–NLRP3 inflammasome cascade, resulting in RGC death. Pharmacological depletion of microglia with PLX5622 could be a potential neuroprotective approach to preserve RGCs from inflammatory cytokines in AAC eyes. Full article