Eye and Brain最新文献

Background: Glaucoma is a neurodegenerative disorder characterized with optic nerve injury and the loss of retinal ganglion cells (RGCs). Ferroptosis has been proved to be associated with the degradation of RGCs. The aim of this study is to elucidate the relationship between ferroptosis and glaucoma pathogenesis, and unveil the underlying mechanism.

Methods: Methyl thiazolyl tetrazolium (MTT) assay was used to evaluate the proliferation of RGCs. The accumulation of cellular iron was measured by Iron assay kit, and the level of reactive oxygen species (ROS) was detected by fluorescence probe. The mitochondrial morphology and autophagosomes were analysed by using transmission electron microscopy (TEM). The contents of glutathione (GSH) and malondialdehyde (MDA) were tested by a GSH assay kit and an MDA detection kit, respectively. The expression of autophagy-related proteins was detected by Western blotting.

Results: A serious cell damage, aberrant iron homeostasis, and oxidative stress was shown in RGC-5 after oxygen-glucose deprivation/reoxygenation (OGD/R) treatment and gamma-Glutamyl transpeptidase 1 (GGT1) knockdown, but these effects were significantly alleviated by overexpression of GGT1 or ferroptosis inhibitors. The TEM and immunofluorescent results indicated that mitochondria impairment and autophagosome accumulation in OGD/R-treated cells was improved after GGT1 overexpression, while the phenomenon in GGT1-silenced cells was aggravated. Furthermore, we found that GGT1 can interact with glutamate cysteine ligase catalytic subunit (GCLC) to inhibit autophagy and ferroptosis in RGC-5 cells.

Conclusion: GGT1 represses autophagy in RGC-5 cells by targeting GCLC, which further restrains the development of ferroptosis in cells.

Whereas excitation and inhibition of neurons are well understood, it is clear that neuromodulatory influences on neurons and their synapses play a major role in shaping neural activity in the brain. Memory and learning, emotional and other complex behaviors, as well as cognitive disorders have all been related to neuromodulatory mechanisms. A number of neuroactive substances including monoamines such as dopamine and neuropeptides have been shown to act as neuromodulators, but other substances thought to play very different roles in the body and brain act as neuromodulators, such as retinoic acid. We still understand little about how neuromodulatory substances exert their effects, and the present review focuses on how two such substances, dopamine and retinoic acid, exert their effects. The emphasis is on the underlying neuromodulatory mechanisms down to the molecular level that allow the second order bipolar cells and the output neurons of the retina, the ganglion cells, to respond to different environmental (ie lighting) conditions. The modulation described affects a simple circuit in the outer retina, involves several neuroactive substances and is surprisingly complex and not fully understood.

Cerebrospinal fluid disorders have a wide-ranging impact on vision, headache, cognition and a person's quality of life. Due to advances in technology and accessibility, intracranial pressure measurement and monitoring, usually managed by neurosurgeons, are being employed more widely in clinical practice. These developments are of direct importance for Ophthalmologists and Neurologists because the ability to readily measure intracranial pressure can aide management decisions. The aim of this review is to present the emerging evidence for intracranial pressure measurement methods and interpretation that is relevant to Neuro-ophthalmologists.

Parkinson's disease (PD) affects approximately 10 million individuals worldwide. Visual impairments are a common feature of PD. Patients report difficulties with visual scanning, impaired depth perception and spatial navigation, and blurry and double vision. Examination of PD patients reveals abnormal fixational saccades, strabismus, impaired convergence, and abnormal visually-guided saccades. This review aims to describe objective features of abnormal eye movements in PD and to discuss the structures and pathways through which these abnormalities may manifest.

Purpose: The retina has potential as a biomarker of brain health and Alzheimer's disease (AD) because it is the only part of the central nervous system which can be easily imaged and has advantages over brain imaging technologies. Few studies have compared retinal and brain measurements in a middle-aged sample. The objective of our study was to investigate whether retinal neuronal measurements were associated with structural brain measurements in a middle-aged population-based cohort.

Participants and methods: Participants were members of the Dunedin Multidisciplinary Health and Development Study (n=1037; a longitudinal cohort followed from birth and at ages 3, 5, 7, 9, 11, 13, 15, 18, 21, 26, 32, 38, and most recently at age 45, when 94% of the living Study members participated). Retinal nerve fibre layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) thickness were measured by optical coherence tomography (OCT). Brain age gap estimate (brainAGE), cortical surface area, cortical thickness, subcortical grey matter volumes, white matter hyperintensities, were measured by magnetic resonance imaging (MRI).

Results: Participants with both MRI and OCT data were included in the analysis (RNFL n=828, female n=413 [49.9%], male n=415 [50.1%]; GC-IPL n=825, female n=413 [50.1%], male n=412 [49.9%]). Thinner retinal neuronal layers were associated with older brain age, smaller cortical surface area, thinner average cortex, smaller subcortical grey matter volumes, and increased volume of white matter hyperintensities.

Conclusion: These findings provide evidence that the retinal neuronal layers reflect differences in midlife structural brain integrity consistent with increased risk for later AD, supporting the proposition that the retina may be an early biomarker of brain health.

Ocular myasthenia gravis (OMG) is a neuromuscular disease characterized by autoantibody production against post-synaptic proteins in the neuromuscular junction. The pathophysiological auto-immune mechanisms of myasthenia are diverse, and this is governed primarily by the type of autoantibody production. The diagnosis of OMG relies mainly on clinical assessment, the use of serological antibody assays for acetylcholine receptors (AchR), muscle-specific tyrosine kinase (MusK), and low-density lipoprotein 4 (LPR4). Other autoantibodies against post-synaptic proteins, such as cortactin and agrin, have been detected; however, their diagnostic value and pathogenic effect are not yet clearly defined. Clinical tests such as the ice test and electrophysiologic tests, particularly single-fiber electromyography, have a valuable role in diagnosis. The treatment of OMG is primarily through cholinesterase inhibitors (pyridostigmine), and steroids are frequently required in cases of ophthalmoplegia. Other immunosuppressive therapies include antimetabolites (azathioprine, mycophenolate mofetil, methotrexate) and biological agents such as B-cell depleting agents (Rituximab) and complement inhibitors (eculizumab). Evidence is scarce on the effect of immunosuppressive therapy on altering the natural course of OMG. Clinicians must be vigilant of a myasthenic syndrome in patients using immune-check inhibitors. Reliable and consistent biomarkers are required to assess disease severity and response to therapy to optimize the management of OMG. The purpose of this review is to summarize the current trends and the latest developments in diagnosing and treating OMG.

Horner's syndrome (HS) is caused by a damage to the oculosympathetic pathway. HS may be congenital, but it is usually acquired and may reveal a life-threatening condition. According to the anatomic location of the underlying pathologic process, HS is classified as central, pre- or postganglionic, when the lesion affects the first, second or third-order neuron, respectively. Pharmacological testing, if available, can be used to differentiate HS from « pseudo-HS » in patients with mild symptoms. Given the financial burden that imaging of the entire oculosympathetic pathway represents, a targeted imaging approach is advised. Although in the majority of cases, clinical examination may predict etiology, in other cases pharmacological testing can help in the localization process. We searched PubMed data base for papers published before December 2022 that concerned Horner's syndrome, its neuro-ophthalmological manifestations and diagnosis. In this article, we describe the main neuro-ophthalmological manifestations of the three types of HS, the most common etiologies, and a targeted diagnostic strategy in each type.

Pineal germinomas can be very complex in terms of presentation, diagnosis, and management. This review attempts to simplify this complexity in an organized manner, addressing the anatomic relationships that provide the basis for the uniqueness of pineal germinoma. Ocular findings and signs and symptoms of elevated intracranial pressure are the keys to suspecting the diagnosis and obtaining the necessary imaging and cerebrospinal fluid studies. Other symptoms can suggest spread beyond the pineal region. Surgery may only be needed to obtain tissue for a definitive diagnosis, as germinoma is highly responsive to chemotherapy and focused radiation therapy. Hydrocephalus, usually related to tumor obstruction of the cerebral aqueduct, may also need to be addressed. Outcome for pineal germinoma is usually excellent, but relapse can occur and may require additional intervention. These issues are detailed in this review.

Purpose: To identify ophthalmic findings in Alzheimer's type dementia (ATD) compared to normal subjects.

Patients and methods: This comparative descriptive study included participants from the institution's cognitive fitness center. Complete ophthalmic examinations were performed. Optical coherence tomography (OCT) and OCT angiography (OCTA) were used to analyze retinal thickness and vascular density. The Ocular Surface Disease Index (OSDI) score and tear breakup time (TBUT) were used to assess dry eye. The blink rate was counted by a well-trained observer. Cognitive function was evaluated using the Thai Mental State Examination (TMSE) score. Correlation analysis was performed to compare OCT, OCTA parameters, and TMSE.

Results: We included 24 ATD patients and 39 normal participants as a control group by age and sex-matched. The prevalence of dry eye using the Asia Dry Eye Society criteria was 15% and 13% in normal and ATD patients, respectively. The differences in OSDI scores, TBUT, and blink rate between the two groups were not statistically significant. The parafoveal and perifoveal macular thickness of the ATD group were significantly lower than that of the control group (p<0.01). All parameters of the vessel density of the ATD group were significantly lower than in the control group, including the whole macular vessel density (p<0.01), optic disc vessel density at the nerve head level (p<0.01), and optic disc vessel density at the radial peripapillary capillary level (p<0.05). After age adjustment, there were no statistically significant differences in all the OCT and OCTA parameters. There was a positive correlation between retinal thickness and vessel density in the macular and optic disc region and TMSE scores.

Conclusion: Perifoveal and parafoveal retinal thickness might be more sensitive than peripapillary RNFL thickness to detect neurodegenerative changes in patients with ATD. Macular thickness and vessel density reduction were also positively correlated with cognitive decline.

Glaucoma is one of the main causes of irreversible blindness in the world. The most common form, primary open-angle glaucoma, is an optic neuropathy that is characterized by a progressive loss of retinal ganglion cells and their axons, leading to structural changes in the optic nerve head and associated visual field defects. Elevated intraocular pressure remains the most important modifiable risk factor for primary open-angle glaucoma. However, a significant proportion of patients develop glaucomatous damage in the absence of increased intraocular pressure, a condition known as normal-tension glaucoma (NTG). The pathophysiology underlying NTG remains unclear. Several studies have revealed that vascular and cerebrospinal fluid (CSF) factors may play significant roles in the development of NTG. Vascular failure caused by functional or structural abnormalities, and compartmentation of the optic nerve subarachnoid space with disturbed CSF dynamics have been shown to be associated with NTG. In the present article, based on the concept of the glymphatic system and observations in patients with NTG, we hypothesize that failure of fluid transport via the glymphatic pathway in the optic nerve may be involved in the pathogenesis of some if not many cases of NTG. According to this hypothesis, vascular and CSF factors may share reduced glymphatic transport and perivascular waste clearance in the optic nerve as a final common pathway leading to the development of NTG. In addition, we speculate that some cases of NTG may reflect glymphatic dysfunction in natural brain aging and central nervous system diseases, such as Alzheimer's disease. Clearly, further studies are needed to gain additional insight into the relative contribution of these factors and conditions to reduced glymphatic transport in the optic nerve.