Melitidin alleviates escitalopram-induced sub-chronic cardiotoxicity via regulating mitochondrial fission-fusion machinery and redox signaling: A biochemical, echocardiographic, and histological study.

Generation and characterization of the hiPSC line CSSi023-A (16154) from a patient with ADOA caused by an OPA1 variant.

Mitochondria transplantation preserves retinal ganglion cells and promotes CNS axonal regeneration.

DNM1L-related disorders are rare mitochondrial diseases characterized by defective fission dynamics, often presenting with severe neurological manifestations. Current diagnostic and prognostic challenges stem from incomplete knowledge of domain-specific genotype-phenotype correlations and limited clinical data. We report a novel GTPase effector domain (GED) variant (p.Val687del) and conduct a systematic analysis of 80 reported DNM1L cases with variants in the GTPase, Middle, or GED domains. Clinical, genetic, and survival data were extracted and analyzed to evaluate associations between mutation localization and clinical outcomes. Statistical comparisons of phenotypic severity, survival, and hotspot prevalence were performed. Functional validation of the novel variant was performed through invitro overexpression, Western blot, immunofluorescence, and transmission electron microscopy. A novel GED deletion (p.Val687del) associated with peripheral neuropathy was identified, expanding the mutational spectrum. Invitro functional studies confirmed that this variant impairs DRP1 mitochondrial localization and induces severe ultrastructural damage, including fragmentation, swelling, and vacuolation. The preserved protein expression level excludes haploinsufficiency, consistent with a dominant-negative mechanism. Within the total cohort of 81 patients (including our case), de novo variants were predominant (74.1%), with R403C representing a major mutational hotspot (28.4%). Middle domain mutations conferred the most severe prognosis, manifesting high frequencies of developmental delay (90.7%), epilepsy (83.7%), abnormal muscle tone (67.4%), abnormal EEG findings (74.4%), and cerebral atrophy (73.2%). In contrast, GTPase domain mutations primarily affected sensory pathways, with optic atrophy (57.6%) and peripheral neuropathy (27.3%) as hallmark features. Carriers of the R403C variant exhibited a 3.9-year delay in disease onset compared to non-carriers. This study establishes that mutation location in DNM1L dictates clinical severity, with Middle domain variants defining a severe encephalopathic subtype, while GTPase domain mutations predominantly target sensory pathways, leading to optic atrophy and peripheral neuropathy. These findings provide a framework for precision prognostication and targeted therapeutic strategies in DNM1L-related disorders.

Objective: To investigate the molecular mechanism of toll-like receptor adaptor protein SARM1 in glaucomatous optic neuropathy. Methods: The experimental study was conducted from February 2024 to October 2025. A chronic ocular hypertension glaucoma model was established by injecting micro-magnetic beads into the anterior chamber of 8- to 10-week-old male Wistar rats. At 3 days, 1 week, and 2 weeks post-modeling, retinal and optic nerve tissues from 6 eyes of 6 rats were collected as the chronic ocular hypertension glaucoma model group, and 6 eyes from 6 wild-type rats that received an equal volume of saline via anterior chamber injection served as the control group. Intraocular pressure was measured using a TonoLab tonometer. Retinal whole-mounts were prepared and POU domain class 4 transcription factor 1 (POU4F1 or Brn3A) immunofluorescence staining was used to detect retinal ganglion cell loss. Western blotting was performed to detect the expression levels of SARM1 and SNPH in the rat retina and optic nerve. Immunofluorescence staining was used to examine their distribution in these tissues. Furthermore, CRISPR/Cas9 technology was used to knock down the expression of SARM1 and SNPH in mouse 661W retinal ganglion cells, respectively. Cells were collected 48 hours after transfection, and Western blotting was performed to detect the expression levels of SARM1 and SNPH. Normally distributed continuous data are presented as mean±SEM. Comparisons between two groups were performed using the Student's t-test, while comparisons among multiple groups were assessed by the one-way analysis of variance followed by the Tukey's multiple comparisons test. Results: Western blot analysis revealed that in the glaucoma model group, the relative expression level of SARM1 protein in the optic nerve at one week post-modeling (1.22±0.06) was significantly higher than that in the control group (1.03±0.01; P=0.027, q=4.38). In contrast, the expression level of SARM1 in the retina at three days post-modeling (0.79±0.02) was significantly lower than that in the control group (1.04±0.03; P<0.001, q=6.86). Concurrently, the expression level of SNPH at three days post-modeling (0.74±0.01) was lower than that in the control group (1.03±0.04; P=0.040, q=0.58), and its expression at one week post-modeling (1.19±0.10; P=0.002, q=4.36) was significantly higher than that at three days (0.74±0.01). Consistent with the Western blot results, immunofluorescence staining results showed that in the optic nerve of the glaucoma model group, the expression of SARM1 was significantly higher than that in the control group at one week post-modeling, while the expression of SNPH was lower than that in the control group at three days post-modeling. Both proteins partially co-localized with the neuronal marker β3-tubulin. Immunofluorescence staining also revealed co-localization of these two proteins within axons. Additionally, SARM1 co-localized with the mitochondrial marker protein TOM20. Western blot results from 661W cells showed that the knockdown of SARM1 expression (0.54±0.04) significantly reduced SNPH expression (0.54±0.05; P=0.003, q=7.98), whereas the knockdown of SNPH expression (0.39±0.06) did not markedly affect SARM1 levels (0.75±0.05; P=0.010, q=6.39). Conclusion: The elevated expression of SARM1 protein in the axons of the rat glaucoma model can promote retinal ganglion cell axonal pathology by localizing to axonal mitochondria and regulating SNPH expression.

Neuro-ophthalmic disorders feature complex etiology. Certain ocular manifestations may hint at severe neurological diseases. Current clinical practice faces no shortage of diagnostic examinations. The core challenge consists in inadequate recognition, integration and interpretation of multifaceted information during initial consultation and non-specialist visits, potentially resulting in misdiagnosis, missed diagnosis, delayed referral and excessive examinations. Artificial intelligence has demonstrated promising performance in optic disc lesion detection, image interpretation of optic neuropathy, visual field analysis, as well as eye movement and pupillary function evaluation. Nevertheless, AI is not intended to replace specialists to deliver definitive diagnoses. Instead, it helps boost early detection of high-risk signs, facilitates analysis of complicated test results, and aids clinical decision-making, patient referral and follow-up management. This article elaborates on the application prospects, existing dilemmas and translational strategies of artificial intelligence in neuro-ophthalmology, aiming to offer references for relevant research and clinical practice.

Evaluation of automated machine learning platforms against an expert-designed deep learning model for optic disc abnormality detection

2-oxyglutarate dehydrogenase (OGDH) encodes an E1 component of α-ketoglutarate dehydrogenase complex that plays a pivotal role in the Krebs cycle. Biallelic variants in OGDH have been reported to cause an early-onset neurodevelopmental and mitochondrial disorder. However, monoallelic OGDH variants have not been associated with human disease. Here, we identified de novo c.1909C>T (p.Arg637Trp) and heterozygous c.162T>G (p.Ser54Arg) variants in OGDH in unrelated individuals exhibiting late-onset neurological phenotypes, characterized by cerebellar ataxia, peripheral neuropathy and optic atrophy. In silico protein structure predictions suggest that the p.Arg637Trp mutation might influence protein function. To determine the functional effects of the OGDH variants invivo, we generated Drosophila models harboring UAS-dOgdh (p.Arg639Trp) and UAS-dOgdh (p.Thr58Arg) mutations, homologous to the human variants. While the mutant OGDH expression did not lead to defects in development, it did lead to age-dependent locomotion defects. Further, we found that p.Arg639Trp mutant leads to defective OGDH activity, while p.Thr58Arg causes abnormal proteolytic cleavage and impaired mitochondrial import. These findings suggest that the variants act as dominant-negative and toxic gain-of-function mutations, respectively. Our data provide evidence that monoallelic OGDH variants are involved in late-onset neurological disease in humans.

We report a rare family of optic atrophy diseases associated with mitochondrial DNA G8363A transfer ribonucleic acid (RNA) cleavage mutations. This family does not exhibit the characteristic symptoms of myoclonic epilepsy or cutaneous lipomas, but instead presents with bilateral optic atrophy. The clinical presentation in this family is highly atypical compared to previous reports.

To determine whether physalin A (PA) safeguards the outer blood-retinal barrier under diabetic stress by engaging nuclear factor erythroid 2-related factor 2 (Nrf2) to restore redox balance and restrain ferroptosis in human retinal pigment epithelial (hRPE) cells and C57BLKS/J Iar -+Leprdb/+Leprdb mice. In high-glucose challenged hRPE cells, PA dose-dependently preserved viability, maintained claudin-1/occludin/zonula occludens-1 abundance and membrane localization, and reversed ferroptosis hallmarks (restored solute carrier family 7 member 11 [SLC7A11], SLC3A2, and glutathione peroxidase 4; reduced ferrous iron [Fe2+] overload and lipid peroxidation). PA restored glutathione levels, reduced malondialdehyde (MDA), and enhanced the antioxidant defense pathway mediated by Nrf2, including upregulation of heme oxygenase 1, NAD(P)H quinone dehydrogenase 1, and superoxide dismutase 2. Silencing Nrf2 abolished the effects of PA on barrier integrity and ferroptosis suppression, with rebounds in reactive oxygen species, MDA, Fe2+, and tight junction loss. In db/db mice treated systemically for 20 weeks, PA reduced Evans Blue leakage, increased retinal thickness, restored RPE tight junction proteins, and normalized mitochondrial architecture by transmission electron microscopy. PA rebalanced mitochondrial dynamics (dynamin 1-like, optic atrophy 1, fission 1, mitofusin 1, FUN14 domain containing 1), increased retinal mitochondrial DNA copy number, and partially stabilized glycemia and weight. PA restores redox tone, restrains ferroptosis, and preserves junctional integrity to protect the diabetic retina, with Nrf2 being indispensable for these benefits. These findings position PA as a promising adjunctive candidate for early diabetic retinopathy and support Nrf2-centered strategies to reinforce the outer blood-retinal barrier. Antioxid. Redox Signal. 45, 5-27.

Impact of compound heterozygous SDHA variants on mitochondrial function in pediatric with neurological disease.

Cross-linked actin networks (CLANs) and their role in the trabecular meshwork.

Quantitative Analysis of Choroidal Thickness and Blood Flow in Thyroid-Associated Ophthalmopathy Using Ultra-Widefield Swept-Source OCT Angiography.

Mitochondrial diseases have traditionally been viewed as energy deficiencies, but current evidence positions mitochondria as central regulators of multiple cell death pathways. This review systematically analyzes the molecular mechanisms of apoptosis and ferroptosis in the context of both primary mitochondrial diseases—caused by mutations in mtDNA or nuclear DNA directly affecting oxidative phosphorylation—and secondary mitochondrial dysfunction associated with broader pathological conditions. Apoptosis is an energy-dependent process characterized by mitochondrial outer membrane permeabilization, cytochrome c release, and caspase cascade activation, whereas ferroptosis involves iron-dependent lipid peroxidation, glutathione depletion, and inactivation of glutathione peroxidase 4 (GPX4), leading to accumulation of oxidized phospholipids predominantly in endoplasmic reticulum and plasma membranes; mitochondrial ultrastructural changes—including volume reduction and cristae loss—represent characteristic morphological features of ferroptosis rather than its primary site of initiation. Key findings reveal that reactive oxygen species overproduction, disruption of reducing equivalent metabolism, iron dyshomeostasis, and calcium overload simultaneously prime cells for both death pathways. Cytochrome c, p53, and BCL-2 family proteins serve as integration hubs, with cardiolipin peroxidation and phospholipid composition influencing pathway switching. Tissue specificity is pronounced in primary mitochondrial diseases: retinal ganglion cells in Leber’s hereditary optic neuropathy, cardiomyocytes in mtDNA-associated cardiomyopathies, and hepatocytes in mtDNA depletion syndromes exhibit distinct dominant death pathways. It should be noted, however, that for many conditions discussed, the evidence for ferroptosis involvement relies on indirect markers—such as lipid peroxidation products, decreased GPX4, and iron deposition—rather than on pharmacological rescue with ferrostatin-1 or liproxstatin-1 and rigorous exclusion of alternative death modalities; this limitation is discussed critically throughout the review. Diagnostic criteria combining morphological, biochemical, and pharmacological tools enable differentiation of death pathways. The review concludes that combined inhibition—using mitochondria-targeted antioxidants, GPX4 modulators, iron chelators, and mPTP blockers—together with personalized diagnostic algorithms offers the most promising therapeutic strategy. Understanding the apoptosis–ferroptosis crosstalk is essential for developing targeted interventions in mitochondrial diseases.

Patient perspectives on gaps in care for vision loss due to Leber hereditary optic neuropathy: A qualitative study

Integrated molecular and clinical profiling of primary mitochondrial oxidative phosphorylation disorders in an Indian cohort: Insights from genetics, neuroimaging, and machine learning.

Glaucoma is a chronic and progressive optic neuropathy, necessitating lifelong monitoring for affected individuals. Traditional surveillance of the disease relies on evaluation of intraocular pressure (IOP), optic nerve anatomy, and visual function at the physician's office, which only provides limited snapshots of a disease characterized by dynamic physiological variation. Developments in portable ophthalmological technologies and digital health platforms have enabled home monitoring of glaucoma. This review synthesizes current evidence on the home monitoring of glaucoma, with a focus on self-tonometry and home-based visual field testing. Handheld tonometers such as iCare HOME and iCare HOME2 allow repeated, anesthesia-free self-measurement of IOP in a real-world setting. These devices have demonstrated good agreement with Goldmann applanation tonometry, the gold standard. Home tonometry captures diurnal variations of IOP, thus providing relevant insights for diagnosis and therapeutic decision-making. Home-based visual field testing (eg, tablet-based platforms, virtual reality-based testing) enables frequent, unsupervised functional assessment with repeatability and sensitivity comparable to standard automated perimetry. Increased testing frequency may facilitate earlier detection of rapid progression, particularly in the early stages of disease. Collectively, evidence suggests the feasibility and clinical relevance of these home monitoring modalities. However, patient compliance with testing schedules and cost-effectiveness remain as challenges.

Glaucoma is a progressive, irreversible optic neuropathy that leads to the loss of retinal ganglion cells, vision loss, and blindness. Elevated intraocular pressure (IOP) is the only modifiable risk factor, and topical hypotensive eye drops remain the mainstay of treatment, reducing disease progression by up to 60%. However, patient adherence to therapy remains a significant challenge since this disease is usually asymptomatic in its early stages. Patient preferences and individual characteristics play a key role in adherence. This study aimed to obtain further knowledge about patient preferences regarding glaucoma treatment to better understand factors influencing adherence. A cross-sectional, multicenter survey was conducted in Spain between March and December 2024 among patients with glaucoma receiving topical treatment for more than 6 months. A questionnaire was designed to collect patients' information about their beliefs, preferences, and adherence-related factors. Of 200 participants, 169 valid responses were analyzed. Most patients were aged 51-74years, 60.2% were women, and 71.2% had been on treatment for more than 12months. Although 93.5% recognized the importance of preservatives, only 36.0% reported having received information about them from their ophthalmologist. Preferences between multidose bottles (MDBs, 42.2%) and single-dose units (SDUs, 37.0%) were similar, although younger women (18-30years) showed a preference for SDUs (p < 0.05). Perceived ease of handling was strongly influenced by prior experience. Most patients considered SDUs as more hygienic, whereas MDBs were perceived as more environmentally friendly; nearly 79% valued ecological impact. Self-reported adherence to therapy was moderate, with 57.6% of participants denying missed doses. Nonadherent patients were more likely to favor reminder systems (74.5%, p = 0.029). Treatment efficacy was ranked as the most important factor, followed by side effects, ease of use, cost, and environmental impact. This study highlights substantial variability in patient preferences and underscores the importance of personalized, patient-centered glaucoma care. Enhanced education on preservatives, improved communication, and sustainable packaging could improve adherence and satisfaction. Larger multicenter studies are needed to confirm these findings and inform long-term adherence strategies.

Type 2 diabetes mellitus (T2DM) and obesity are commonly treated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs). However, there have been growing concerns over the possibility that these medications may result in ocular adverse events, such as nonarteritic anterior ischemic optic neuropathy (NAION). Standard clinical care can overlook these potentially fatal adverse effects. The purpose of this review was to compile the most recent data on ocular side effects associated with GLP-1 RA therapy, assess their clinical relevance, and highlight necessary preventative and monitoring measures. A thorough search of the literature was conducted using Medline/PubMed/PMC, Google Scholar, Scopus, Web of Science, and ScienceDirect. Relevant literature, including observational studies, randomized trials, case reports, and pharmacovigilance data, was selected for its discussion of GLP-1 RAs and associated eye-related adverse events. Semaglutide, a GLP-1 RA, has been associated in a number of studies and safety assessments with an increased risk of NAION and the progression of diabetic retinopathy, especially in patients with underlying eye disorders. Findings, however, were mixed because no statistically significant link was found in a number of cohort studies and meta-analyses. The necessity for additional research was supported by data from adverse event reporting systems that showed disproportionality signals. Clinicians should be mindful of the potential ocular hazards associated with GLP-1 RAs, even though these medications remain useful in treating T2DM and obesity. Closer ophthalmologic monitoring may be beneficial for patients with known diabetic eye problems. Further prospective research with well-defined ocular outcomes is required to elucidate these correlations and guarantee the secure administration of GLP-1 RAs.

Glaucoma is a chronic, progressive optic neuropathy and a leading cause of irreversible blindness worldwide. Structural damage to the retinal nerve fiber layer (RNFL) precedes visual field loss, making RNFL assessment a crucial parameter for early diagnosis. Spectral-domain optical coherence tomography (SD-OCT) enables objective and quantitative evaluation of RNFL thickness, facilitating early detection and monitoring of glaucomatous damage. The aim is to compare retinal nerve fiber layer thickness between glaucomatous and nonglaucomatous patients. This cross-sectional comparative study was conducted in the Department of Ophthalmology at Aarupadai Veedu Medical College and Hospital, Puducherry, from July 2024 to December 2025. A total of 140 participants aged ≥ 40 years were enrolled using consecutive sampling and divided equally into glaucoma (Group A, n = 70) and control groups (Group B, n = 70). Comprehensive ophthalmic evaluation was performed, including intraocular pressure (IOP), gonioscopy, central corneal thickness (CCT), visual fields, and optic disc assessment. RNFL thickness (average and quadrant-wise) was measured using SD-OCT. Independent sample t-test was used to analyze between the two groups using SPSS version 26.0, with significance set at P < 0.05. The mean age was comparable between groups (P = 0.259). Glaucoma patients had significantly higher IOP and cup-to-disc ratio and significantly thinner CCT compared to controls (P < 0.05). RNFL thickness in the superior, inferior, nasal, and temporal quadrants, and average RNFL, was significantly reduced in the glaucoma group compared to controls (P < 0.01). Significant RNFL thinning was observed in glaucomatous patients compared to nonglaucomatous individuals. RNFL measurement using SD-OCT is a reliable and sensitive tool for early detection and evaluation of glaucomatous optic neuropathy.