Optic Nerve Function Research Articles

Safety of and chorioretinal circulation during repeated low-level red-light therapy for myopic children.

To evaluate the safety of repeated low-level red-light (RLRL) therapy in children, and the dynamic evolution of choroidal and retinal blood flow. This is a single-centre, randomised, single-blind, parallel-group clinical trial. Seventy myopic children were randomly assigned to either the intervention group [receiving RLRL therapy plus single-vision spectacle (SVS)] or the control group (wearing SVS). Participants underwent comprehensive ophthalmic examinations following their first irradiation, 9 months continuous RLRL therapy and stop of treatment. Quantitative analyses of choroidal and retinal microcirculation were analysed via optical coherence tomography angiography. Over 9 months of treatment, while the RLRL treatment demonstrated significantly less increases in refractive error and axial length compared with the SVS treatment (ps < 0.05), no abnormalities in fundus structure or visual function (mfERG, VEP and microperimetry) were detected (ps > 0.05). A single red-light exposure did not exert a significant influence on choroidal thickness (ps > 0.05). Upon continuous treatment, the RLRL group achieved peak values in these circulations at 9 months (ps < 0.05). Following cessation of exposure, all circulations exhibited a declining trend, reaching similar levels in both groups (ps > 0.05). As the frequency of red-light exposures intensified, there was a consistent surge in these circulations (ps < 0.05). Nine months of continuous RLRL exposure does not cause toxic side effects on retinal or optic nerve functions, and there is a time-dependent cumulative response in choroidal and retinal circulation.

Visual Outcomes of Children With Craniosynostosis.

Craniosynostosis can impact the visual development of a child. Historically, children with craniosynostosis, particularly when associated with a syndrome, had a significant risk of vision loss. The authors aimed to study the incidence of ophthalmic pathology in a modern, multidisciplinary craniosynostosis practice. Children aged 7 to 13 years attending face-to-face ophthalmic craniofacial clinics between February 2020 and June 2021 were included in a retrospective case note review. Visual acuity, ocular alignment, optic nerve function, and retinal nerve fiber layer (RNFL) condition using optical coherence tomography (OCT) were recorded. Forty-three children (30 girls) were assessed at a median age of 10.3 years (7.8-13.1). Eleven children had unicoronal synostosis, 15 had single-suture synostosis not involving the coronal, 14 had multisuture synostosis involving the coronal, and 3 had multisuture synostosis not involving the coronal. Thirty-two out of 43 had craniofacial surgery. Sixty-seven percent required glasses. Forty-nine percent had strabismus, 11/43 (26%) had squint surgery, and 2/43 (5%) had tarsorrhaphy for corneal protection. Four out of 43 (9%) had papilloedema detected; however, at the final review, 15/68 (22%) eyes showed RNFL changes on OCT imaging, none of whom had optic atrophy. Two children did not meet UK driving standards due to refractive amblyopia; no children were registered as sight impaired. In this cohort, optic atrophy and visual loss due to exposure keratopathy were not seen. A high incidence of strabismus, glasses wear, and amblyopia is persistent. Binocular visual impairment was rare in this cohort: 95% met UK driving standards. Visual outcomes appear to be improving coinciding with improved craniofacial care alongside multidisciplinary team working.

Neuromyelitis optica in a paediatric patient: a case report

Neuromyelitis optica is a multifocal demyelinating disease of the central nervous system that predominantly affects the spinal cord and optic nerves, with variable clinical features including motor weakness in limbs, bowel and bladder affection and loss of vision. The disease is characterized by poor or no recovery. Magnetic resonance imaging (MRI) of spine with contrast shows hyperintense lesions involving contiguous segments with a normal MRI brain. CSF studies shows anti aquaporin 4 antibodies. Visual evoked potential of eyes shows marked reduction of optic nerve function. We report a case of eight year old girl who presented with diminished vision in eyes (right &gt;left) and weakness in all four limbs. Clinical features and investigations were suggestive of NMO. She was treated with inj. methylprednisolone for 5 days followed by oral prednisolone in tapering dose for 6 weeks. The child improved of hemiparetic gait and power in the left side. Vision in the left eye did not deteriorate further. Repeat MRI showed the resolution of previous spinal lesions. Follow up of the child over seven years has multiple admissions due to relapses. In the third admission child was given again 5 days of inj. methylprednisolone followed by azathioprine for two months. On the seventh admission due to relapse, inj. rituximab 500 mg and inj. methylprednisolone 500 mg was given and repeated every 6 months. In the last follow up in June 2024, the child is clinically stable with improvement in gait and no further deterioration of vision and no bowel or bladder affection.

Nicotinamide: Bright Potential in Glaucoma Management.

Glaucoma is a major cause of incurable ocular morbidity and poses significant challenges in its management due to the limited treatment options and potential adverse effects. Nicotinamide, a naturally occurring diet-rich nutrient, has emerged as a promising therapeutic agent for glaucoma, offering neuroprotective effects and the potential modulation of intraocular pressure (IOP) regulation pathways. This comprehensive review sought to analyze the current literature on nicotinamide in glaucoma management, exploring its mechanisms of action, efficacy, and safety profile. A systematic search of the PubMed database was conducted to identify relevant records on the therapeutic actions of nicotinamide in ocular hypertension and glaucoma. Publications evaluating nicotinamide's effects on retinal ganglion cells (RGCs), optic nerve function, IOP regulation, and neuroinflammatory pathways were included. The literature review revealed the preclinical evidence supporting nicotinamide's neuroprotective effects on RGCs, the preservation of optic nerve integrity, and the modulation of glaucoma-associated neuroinflammation. Additionally, nicotinamide may exert IOP-lowering effects through its influence on ocular blood flow and aqueous humor dynamics. Nicotinamide holds promise as a novel therapeutic approach in glaucoma management, offering potential neuroprotective and IOP-lowering effects. The authors recommend more research to determine the nicotinamide efficacy, safe dosing parameters, and any long-term safety concerns in glaucoma patients.

Prophylactic Intravitreal Methotrexate Infusion during Vitrectomy to Prevent Proliferative Vitreoretinopathy in Cases of Rhegmatogenous Retinal Detachment

Abstract Aim To assess the efficacy and safety of intravitreal methotrexate (MTX) infusion (IMI) during pars plana vitrectomy (PPV) in patients with rhegmatogenous retinal detachment (RRD) to prevent proliferative vitreoretinopathy (PVR) in patients with established PVR grade C and patients at high risk for PVR development. Settings and Design A prospective comparative interventional study conducted from September 2020 till November 2021 at Ain Shams University Hospitals, Egypt. Materials and Methods Forty-seven eyes of patients with RRD undergoing PPV were divided into case group receiving IMI during the surgery and control group. Each group was subdivided into a subgroup with high-risk patients to develop PVR and a subgroup with established PVR grade C preoperatively. Outcome measures at the end of three months postoperatively were retinal attachment rate, incidence of PVR, reoperation rate to flatten the retina and the changes in retina and/or optic nerve function assessed by full field electroretinogram (ff-ERG) and flash visually evoked potential (VEP) Results Seven cases (15%) and four cases (9%) developed PVR after one month and three months respectively. Five cases (10 %) required reoperation to re-flatten the retina, 43 cases (91 %) had complete flattening of the retina after three months. No statistically significant differences were reported between the studied groups regarding the studied outcome measures, and no serious adverse events were reported secondary to IMI. Conclusion IMI use was found to be safe in intraocular use, but it did not affect the anatomical success rate. Key words: Proliferative Vitreoretinopathy, Recurrent Retinal Detachment, Electrophysiology. Key Messages: More studies need to be conducted to further evaluate if MTX has a role in the prevention of PVR after vitrectomy.

Novel miRNA targets and characterisation of optic nerve function in a mouse model of hypoperfusion

Novel miRNA targets and characterisation of optic nerve function in a mouse model of hypoperfusion

Pupil cycle time and its significance in patients with diabetic retinopathy

Context: Prolonged pupil cycle time (PCT) is a complication of type II diabetes and becomes more protracted as the disease progresses. PCT can be used as a quick and accurate clinical test to determine how much autonomic neuropathy is influencing a diabetic patient’s pupil. Aims: The aim of the study was to compare the PCT of type II diabetes patients with that of the healthy control group and analyze the impact of several factors, including age, sex, duration of diabetes, and grade of diabetic retinopathy on PCT. Settings and Design: The study was conducted from August 2022 to August 2023. One hundred people were arbitrarily selected, 50 of whom had diabetes and 50 healthy controls. Subjects and Methods: To start rhythmic cycles of contraction and relaxation, a narrow, horizontally aligned beam of fixed proportions was focused on the inferior area of the pupil. The cycle period was then monitored in milliseconds using a handheld stopwatch. The mean PCT of diabetics was compared with nondiabetics and its correlation with different variables such as age, sex, diabetes duration, and grade of retinopathy was done. Results: Fifty diabetic patients (28 females and 22 males) aged 42–74 years and 50 controls (32 females and 18 males) aged 44–70 were included in the study. The mean PCT of the diabetics was 1130 ± 186 ms, whereas it was 940 ± 132 ms in the controls; thus, the mean PCT was longer in the diabetics. It was also found that the mean PCT increased with increasing grades of retinopathy. A positive correlation was also noted between mean PCT and duration of diabetes. Conclusions: PCT is a fast, simple, and reliable clinical test of optic nerve function. Being objective and quantifiable for each eye separately is a huge benefit. The PCT measurements might be used in the clinical evaluation of an autonomic nervous system. It is a simple, inexpensive yet quick, and effective tool to assess pupillary autonomic neuropathy in the diabetics.

High-performance IGZO/In2O3 NW/IGZO phototransistor with heterojunctions architecture for image processing and neuromorphic computing

The development of high-performance neuromorphic phototransistors is of paramount importance for image perception and depth memory learning. Here, based on metal-oxide heterojunction architecture, artificial synaptic phototransistors with synaptic plasticity have been achieved, demonstrating an artificial synapse that integrates central and optic nerve functions. Thanks to the sensitive light-detection properties, the optical power consumption of such photonic artificial synapses can be as low as 22 pico-joules, which is extremely competitive compared with other pure metal oxide photoelectric synapses ever reported. What is more, owing to its good short-term (STP) and tunable amplitude-frequency characteristics, the as-constructed device can function as a biomimetic high-pass filter for picture edge detection. Dual-mode synaptic modulation has been performed, combining photonic pulse with gate voltage stimulus. After photoelectric-synergistic modulation, the high synaptic weights enable the device to simulate complex neural learning rules for neuromorphic applications, including gesture recognition, image perception in the visual system, and classically conditioned reflexes. These results suggest that the current oxide-based heterojunction architecture displays potential application in future multifunction neuromorphic devices and systems.

Investigation of optic nerve function in Behçet's patients with optic disc hyperfluorescence in fundus fluorescein angiography.

The aim was to investigate the changes in optic nerve function that may help in the diagnosis of subclinical optic nerve involvement in patients with Behçet's disease (BD) and isolated optic disc (OD) hyperfluorescence in fluorescein angiography (FA). Three groups were formed; BD patients with isolated OD hyperfluorescence in FA, BD patients without ocular involvement (normal FA) and control group. A total of 88 eyes of 45 patients were included. The groups were compared in terms of OCT-RNFL, contrast sensitivity and VEP latency. When the OCT-RNFL values were compared, there was a significant difference between the control group and Behçet's patients with normal FA. Contrast sensitivity values differed significantly among the groups, and the lowest mean contrast sensitivity was observed in the group with OD hyperfluorescence (p < 0.05). As far as we know, this is the first publication that investigates optic nerve function in BD patients with isolated OD hyperfluorescence in FA. Assessment with FA of asymptomatic BD patients with visual complaints and low contrast sensitivity may be helpful at early detection of inflammatory optic neuropathy by close follow-up in patients with OD hyperfluorescence.

PUPIL CYCLE TIME AND PERIPAPILLARY PERFUSION IN ANGLE CLOSURE GLAUCOMA

Introduction and Objective: One of important roles in the pathogenesis of glaucoma is vascular condition. To enhance glaucoma management, the clinical assessment of ocular perfusion is required. The pupillary light reflex's afferent or efferent pathways may become impaired as a result of pupil cycle time (PCT) elongation. PCT is a simple objective method to measure the function of optic nerve, including glaucoma. The purpose of this study is to evaluate the connection between pupil PCT and peripapillary perfusion. Methods: A cross-sectional study from Kariadi Hospital included 26 eyes with angle closure glaucoma and 26 eyes of healthy patients. Complete ophthalmologic examinations, PCT measurements, and OCT peripapillary angiography were performed on each patient. Patients with history of drugs use that can affect pupillary reflexes such as barbiturates, methyldopa, anaesthetics, and antidepressant, and patients with history of glaucoma attack are excluded. The comparisons between the two groups were examined, with a p&lt;0.05 indicating statistical significance. Results: The mean PCT of normal subjects was 943,4ms (882,4ms – 993,4ms) and angle closure glaucoma subject was 1789,5ms (1060ms – 4600ms). There were statistically significant difference of PCT value in angle closure glaucoma compared to normal subjects (P&lt;0,05). Peripapillary flow index and peripapillary vessel density in closed angle glaucomatous eyes were lower than normal eyes (P&lt;0.05). There is a significant relationship between PCT with peripapillary flow index and peripapillary vessel density. (P&lt;0,05). Conclusion: In angle closure glaucoma, prolonged PCT associated with decreased peripapillary perfusion as shown by decreases in peripapillary flow index and peripapillary vascular density.

PUPIL CYCLE TIME AND PERIPAPILLARY PERFUSION IN ANGLE CLOSURE GLAUCOMA

Introduction &amp; ObjectivesOne of important roles in the pathogenesis of glaucoma is vascular condition. To enhance glaucomamanagement, the clinical assessment of ocular perfusion is required. The pupillary light reflex'safferent or efferent pathways may become impaired as a result of pupil cycle time (PCT) elongation.PCT is a simple objective method to measure the function of optic nerve, including glaucoma. Thepurpose of this study is to evaluate the connection between pupil PCT and peripapillary perfusion.&#x0D; MethodsA cross-sectional study from Kariadi Hospital included 26 eyes with angle closure glaucoma and 26eyes of healthy patients. Complete ophthalmologic examinations, PCT measurements, and OCTperipapillary angiography were performed on each patient. Patients with history of drugs use thatcan affect pupillary reflexes such as barbiturates, methyldopa, anaesthetics, and antidepressant, andpatients with history of glaucoma attack are excluded. The comparisons between the two groupswere examined, with a p&lt;0.05 indicating statistical significance.&#x0D; ResultsThe mean PCT of normal subjects was 943,4ms (882,4ms – 993,4ms) and angle closure glaucomasubject was 1789,5ms (1060ms – 4600ms). There were statistically significant difference of PCTvalue in angle closure glaucoma compared to normal subjects (P&lt;0,05). Peripapillary flow index andperipapillary vessel density in closed angle glaucomatous eyes were lower than normal eyes(P&lt;0.05). There is a significant relationship between PCT with peripapillary flow index andperipapillary vessel density. (P&lt;0,05).&#x0D; ConclusionIn angle closure glaucoma, prolonged PCT associated with decreased peripapillary perfusion asshown by decreases in peripapillary flow index and peripapillary vascular density.

THE CORRELATION BETWEEN NEUTROPHYL-LYMPHOCYTE RATIO AND OPTIC NERVE FUNCTION IN METABOLIC SYNDROME PATIENTS

Background: The neutrophil lymphocyte ratio (NLR) is a new biomarker in predicting various cardiovascular disorders and was expected to be a biomarker for Nonarteritic Anterior Ischemic Optic Neuropathy (NAION) in metabolic syndrome (MetS) patients. Objective: This study aims to determine the correlation between NLR and optic nerve function in MetS patients. Methods: A cross sectional study involving 42 patients divided into 3 groups, consist of control group(14 patients, 28 eyes), MetS without NAION group(14 patients, 28 eyes) and MetS with NAION group(14 patients, 19 eyes). The study was conducted at Saiful Anwar General Hospital on January-March 2019. Optic nerve function evaluation includes visual acuity (VA) from Snellen chart, Retinal Nerve Fiber Layer(RNFL) from OCT, contrast sensitivity from Pelli Robson test, and visual field defect from Humphrey's perimetry. NLR was calculated and compared among groups using anova test. Then the correlation between NLR and optic nerve function was investigated using Pearson and Spearman test. Results: The NLR was significantly different among groups (p= 0.009), mean of control, MetS without NAION, and MetS with NAION groups 1.70, 1.86, and 2.40 respectively. There were signifficant negative correlation between NLR and visual field defect (p= 0.001,r= -0.487), contrast sensitivity (p= 0.015,r= -0.372), and VA (p= 0.041,r= -0.316), whereas positive correlation between NLR and RNFL statistically insignificant (p= 0.171, r = 0.215). Conclusion: There were signifficant negative correlation between NLR and visual field defect, contrast sensitivity, VA, whereas positive correlation between NLR and RNFL statistically insignificant. NLR is expected to be a potential biomarker for screening NAION in MetS patients.

Quantification of Goldmann Visual Fields During Resolution of Traumatic Optic Neuropathy

Purpose: We describe the clinical findings in a Japanese patient with unilateral traumatic optic neuropathy (TON) who underwent steroid pulse therapy followed by optic canal decompression surgery. The optic nerve function was assessed longitudinally and quantitatively by Goldmann visual fields (GVFs). This was accomplished by measuring the area of each isopter and scotoma, and the findings were compared with the visual acuities recorded during the course of the resolution of the TON.Case Presentation: A 70‐year‐old man suffered from TON in his left eye after falling from a 3 m cliff. On examination at the Saitama Medical University Hospital, his decimal best corrected visual acuity (BCVA) in his left eye was 0.2. Computed tomography revealed a fracture of the lateral wall of the left orbit, but no obvious optic canal fracture was observed. Steroid pulse therapy was started, and optic nerve decompression surgery was performed. After steroid administration, there was a slight improvement in the visual acuity, and a response in the I/3e isopter was present (area 17.76 deg2). However, the V/4e area decreased from 539.35 to 359.36 deg2. Three days after the optic canal decompression surgery, the decimal visual acuity improved to 0.6, and the V/4e area and I/3e area increased to 1122.52 and 46.88 deg2, respectively. Postoperatively, there was a marked improvement in the size of the GVFs that corresponded to the improved visual acuity. The visual acuity of the left eye was 0.8 after 6 months, and the GVF was still not completely normal.Conclusions: Our findings showed the course of recovery of the visual acuity and visual field in an eye with TON. The quantification of GVF was helpful in assessing the course of recovery after the treatments. The new quantitative index of the GVFs may be helpful in evaluating the effectiveness of treatments for optic nerve disorders.

Compressive Optic Neuropathy (CON) Secondary to Inflammatory Polyp Mimicking Lymphoma: A Rare Manifestation

Introduction: Compressive optic neuropathy (CON) is the impairment of optic nerve function by space-occupying lesions that mechanically compress the optic nerve or optic tract. CON can arise from either intrinsic or extrinsic compression, and determining the underlying cause is important to approach the correct management. The objective of this case report is to present a rare case of CON secondary to an inflammatory polyp that mimicking lymphoma. Case Presentation: A 68-year-old male patient came to the neuro-ophthalmology clinic with a chief complaint of blurry vision in his left eye since three months ago that was getting worse until he lost his vision accompanied by drooping of the upper left eyelid. He also felt pain in his left eye, nausea, vomiting, and headache. Visual acuity of the right eye was 5/5 and the left eye had no light perception. Ocular motility of the left eye was restricted in all gaze. The pupil was 6 mm with no light reflex, and edema in the optic nerve head in the left eye was found from the posterior segment. The patient's MRI showed soft tissue thickening on the left orbital apex – left optic canal – left anterior cavernous sinus and enlargement of left medial rectus muscle with encasement of the left optic nerve, and from post-contrast showed contrast enhancement that suggested a lymphoma. He was diagnosed with CON secondary to lymphoma and was given Methylprednisolone 32 mg three times a day orally. Conclusions: Several differential diagnoses resemble the findings of CON secondary to inflammatory polyp. Some diagnostic examination must be done to exclude the other diagnosis to give a proper treatment for the patient.

ScAAV2-Mediated Expression of Thioredoxin 2 and C3 Transferase Prevents Retinal Ganglion Cell Death and Lowers Intraocular Pressure in a Mouse Model of Glaucoma.

Elevated intraocular pressure (IOP) in glaucoma causes retinal ganglion cell (RGC) loss and damage to the optic nerve. Although IOP is controlled pharmacologically, no treatment is available to restore retinal and optic nerve function. In this paper, we aimed to develop a novel gene therapy for glaucoma using an AAV2-based thioredoxin 2 (Trx2)-exoenzyme C3 transferase (C3) fusion protein expression vector (scAAV2-Trx2-C3). We evaluated the therapeutic effects of this vector in vitro and in vivo using dexamethasone (DEX)-induced glaucoma models. We found that scAAV2-Trx2-C3-treated HeLa cells had significantly reduced GTP-bound active RhoA and increased phosphor-cofilin Ser3 protein expression levels. scAAV2-Trx2-C3 was also shown to inhibit oxidative stress, fibronectin expression, and alpha-SMA expression in DEX-treated HeLa cells. NeuN immunostaining and TUNEL assay in mouse retinal tissues was performed to evaluate its neuroprotective effect upon RGCs, whereas changes in mouse IOP were monitored via rebound tonometer. The present study showed that scAAV2-Trx2-C3 can protect RGCs from degeneration and reduce IOP in a DEX-induced mouse model of glaucoma, while immunohistochemistry revealed that the expression of fibronectin and alpha-SMA was decreased after the transduction of scAAV2-Trx2-C3 in murine eye tissues. Our results suggest that AAV2-Trx2-C3 modulates the outflow resistance of the trabecular meshwork, protects retinal and other ocular tissues from oxidative damage, and may lead to the development of a gene therapeutic for glaucoma.

A new model of axon degeneration in the mouse optic nerve using repeat intraocular pressure challenge

We characterize a new experimental model for inducing retinal ganglion cell (RGC) dysfunction and degeneration in mice. C57BL/6J mice were subjected to two acute periods of intraocular pressure (IOP) elevation (50 mmHg for 30 min) by cannulation of the anterior chamber. We used full-field electroretinography and visual evoked potentials (VEPs) to measure subsequent changes in retina and optic nerve function, and histochemical techniques to assess RGC survival and optic nerve structure. In 12 month old mice, a single IOP challenge caused loss and subsequent recovery of RGC function over the following 28 days with minimal cell death and no observed axonal damage. A second identical IOP challenge resulted in persistent RGC dysfunction and significant (36%) loss of RGC somas. This was accompanied by a 16.7% delay in the latency and a 27.6% decrease in the amplitude of the VEP. Severe axonal damage was seen histologically with enlargement of axons, myelin disruption, reduced axon density, and the presence of glial scarring. In contrast, younger 3 month old mice when exposed to a single or repeat IOP challenge showed quicker RGC functional recovery after a single challenge and full functional recovery after a repeat challenge with no detectable optic nerve dysfunction. These data demonstrate a highly reproducible and minimally invasive method for inducing RGC degeneration and axonal damage in mice. Resilience of the optic nerve to damage is highly dependent on animal age. The time-defined nature of functional versus structural loss seen in this model stands to facilitate investigation of neuroglial responses in the retina after IOP injury and the associated evaluation of neuroprotective treatment strategies. Further, the model may be used to investigate the impact of aging and the cellular switch between neurorecovery and neurodegeneration.

Assessment of retinal and choroidal vessel density and nerve fibre layer thickness changes after orbitotomy in patients with severe non-active thyroid orbitopathy: a prospective study.

To evaluate the optical coherence tomography angiogram changes in non-active severe thyroid-related ophthalmopathy patients after cosmetic bone decompression. Eighteen patients (25 eyes) with severe not active not compressive (NANC) TED who were candidates for decompression surgery for cosmetic reasons were included in this study, and a 3 × 3mm macular scan was used to measure vessel density and RNFL thickness. Whole macular vessel density in its superficial, deep and choriocapillaris layers was evaluated. The following data were extracted for each of layers: superior and inferior hemispheres, fovea, parafoveal vessel density, its superior and inferior hemispheres, and temporal, superior, nasal and inferior quadrant. The mean RPC increased postoperatively, which was statistically significant in small vessels of peripapillary area (p-value = 0.045). The mean RNFL thickness decreased after surgery and it was statistically significant in the peripapillary (p-value = 0.032) and Inferior-Hemifield area (p-value = 0.036). The choriocapillaris changes were significant in Superior-Hemifield (p-value = 0.031) and Fovea (p-value = 0.03). Thyroid-associated orbitopathy patients have a tendency to decrease vascular density and correlated with disease activity more than stage of orbitopathy. There was not a strong and even discrepant result in linkage of RNFL thickness and other optic nerve function tests and TED patient status and it is needed to do studies with more epidemiologic power and same methodology of study to be more comparable.

Acriflavine, a HIF-1 inhibitor, preserves vision in an experimental autoimmune encephalomyelitis model of optic neuritis.

Optic neuritis (ON) is often an early sign of multiple sclerosis (MS), and recent studies show a link between HIF-1 pathway activation and inflammation. This study aimed to determine if inhibition of the HIF-1 pathway using the HIF-1a antagonist acriflavine (ACF) can reduce clinical progression and rescue the ocular phenotype in an experimental autoimmune encephalomyelitis (EAE) ON model. EAE-related ON was induced in 60 female C57BL/6J mice by immunization with MOG33-55, and 20 EAE mice received daily systemic injections of ACF at 5 mg/kg. Changes in the visual function and structure of ACF-treated EAE mice were compared to those of placebo-injected EAE mice and naïve control mice. ACF treatment improved motor-sensory impairment along with preserving visual acuity and optic nerve function. Analysis of retinal ganglion cell complex alsoshowed preserved thickness correlating with increased survival of retinal ganglion cells and their axons. Optic nerve cell infiltration and magnitude of demyelination were decreased in ACF-treated EAE mice. Subsequent in vitro studies revealed improvements not only attributed to the inhibition of HIF-1 butalso to previously unappreciated interaction with the eIF2a/ATF4 axis in the unfolded protein response pathway. This study suggests that ACF treatment is effective in an animal model of MS via its pleiotropic effects on the inhibition of HIF-1 and UPR signaling, and it may be a viable approach to promote rehabilitation in MS.

Bionic optic nerve based on perovskite (CsPbBr 3) quantum-dots

The bionic optic nerve can mimic human visual physiology and is a future treatment for visual disorders. Photosynaptic devices could respond to light stimuli and mimic normal optic nerve function. By modifying (Poly(3,4-ethylenedioxythio-phene):poly (styrenesulfonate)) active layers with all-inorganic perovskite quantum dots, with an aqueous solution as the dielectric layer in this paper, we developed a photosynaptic device based on an organic electrochemical transistor (OECT). The optical switching response time of OECT was 3.7 s. To improve the optical response of the device, a 365 nm, 300 mW·cm -2 UV light source was used. Basic synaptic behaviors such as postsynaptic currents (0.225 mA) at a light pulse duration of 4 s and double pulse facilitation at a light pulse duration of 1 s and pulse interval of 1 s were simulated. By changing the way light stimulates, for example, by adjusting the intensity of the light pulses from 180 to 540 mW·cm -2, the duration from 1 to 20 s, and the number of light pulses from 1 to 20, the postsynaptic currents were increased by 0.350 mA, 0.420 mA, and 0.466 mA, respectively. As such, we realized the effective shift from short-term synaptic plasticity (100 s recovery of initial value) to long-term synaptic plasticity (84.3% of 250 s decay maximum). This optical synapse has a high potential for simulating the human optic nerve.

Loss of optic nerve oligodendrocytes during maturation alters retinal organization

The myelin sheath facilitates signal conduction along axons in white matter tracts, and when disrupted, can result in significant functional deficits. Demyelination, observed in diseases like multiple sclerosis and optic neuritis, are associated with neural degeneration, however the extent of this damage on upstream circuitry is not well understood. Here we use the MBP-iCP9 mouse model to induce selective oligodendrocyte ablation in the optic nerve at P14 via a chemical inducer of dimerization (CID), resulting in partial demyelination of retinal ganglion cell (RGC) axons with minimal inflammation after two weeks. Oligodendrocyte loss reduced axon diameter and altered compound action potential waveforms, blocking conduction in the slowest-conducting axon populations. Demyelination resulted in disruptions to the normal composition of the retina, including reduced density of RBPMS+, Brn3a+, and OFF-transient RGCs, thinning of the IPL, and reduced density of displaced amacrine cells. The INL and ONL were unaffected by oligodendrocyte loss, suggesting that demyelination-induced deficits in this model are specific to the IPL and GCL. These results show that a partial demyelination of a subpopulation of RGC axons disrupts optic nerve function and affects the organization of the retinal network. This study highlights the significance of myelination in maintaining upstream neural connectivity and provides support for targeting neuronal degeneration in treatments of demyelinating diseases.