IC100, a humanized therapeutic monoclonal anti-ASC antibody alleviates oxygen-induced retinopathy in mice.

Background: Retinopathy of prematurity (ROP), which often presents with bronchopulmonary dysplasia (BPD), is among the most common morbidities affecting extremely premature infants and is a leading cause of severe vision impairment in children worldwide. Activations of the inflammasome cascade and microglia have been implicated in playing a role in the development of both ROP and BPD. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is pivotal in inflammasome assembly.

Mitochondrially Targeted Gene Therapy Rescues Visual Loss in a Mouse Model of Leber's Hereditary Optic Neuropathy.

Leber's hereditary optic neuropathy (LHON) is a common mitochondrial genetic disease, causing irreversible blindness in young individuals. Current treatments are inadequate, and there is no definitive cure. This study evaluates the effectiveness of delivering wildtype human NADH ubiquinone oxidoreductase subunit 4 ) gene using mito-targeted AAV(MTSAAV) to rescue LHOH mice.

The Inflammasome-Dependent Dysfunction and Death of Retinal Ganglion Cells after Repetitive Intraocular Pressure Spikes.

The dysfunction and selective loss of retinal ganglion cells (RGCs) is a known cause of vision loss in glaucoma and other neuropathies, where ocular hypertension (OHT) is the major risk factor. We investigated the impact of transient non-ischemic OHT spikes (spOHT) on RGC function and viability in vivo to identify cellular pathways linking low-grade repetitive mechanical stress to RGC pathology. We found that repetitive spOHT had an unexpectedly high impact on intraocular homeostasis and RGC viability, while exposure to steady OHT (stOHT) of a similar intensity and duration failed to induce pathology.

Leber Hereditary Optic Neuropathy Gene Therapy: Longitudinal Relationships Among Visual Function and Anatomical Measures.

Purpose: To assess longitudinal relationships among visual function and anatomical measures of gene therapy in G11778A Leber hereditary optic neuropathy (LHON).

Design: Phase 1 clinical trial.

Methods: This was a single-institution study of patients with G11778A LHON.

High-Throughput Binocular Pattern Electroretinograms in the Mouse.

The pattern electroretinogram (PERG) reflects the electrical activity of retinal ganglion cells (RGC) and has become the most used technology to assess RGC function in experimental models of glaucoma and optic neuropathies. We describe a novel method for obtaining user-friendly, robust PERG simultaneously from each eye using asynchronous binocular stimulation and one-channel acquisition of signals recorded from a subcutaneous needle in the snout.

Pattern Electroretinogram in Ocular Hypertension, Glaucoma Suspect and Early Manifest Glaucoma Eyes: A Systematic Review and Meta-analysis.

Topic: To provide standardized confidence limits of the transient pattern electroretinogram (tPERG) P50 and N95 and steady state pattern electroretinogram (ssPERG) amplitudes in normal controls as compared to ocular hypertension (OHT), glaucoma suspect (GS), or early manifest glaucoma (EMG) eyes.

Clinical Relevance: The identification of standardized confidence limits in the context of pattern electroretinogram (PERG) might overcome the high intrinsic variability of the measure, and it might lead to a more intuitive understanding of the results as well as to an easier comparison of data from multiple tests, sites, and operators.

Methods: The study protocol was prospectively registered on the International Prospective Register of Systematic Reviews (ID: CRD42022370032).

Comparison of different gene-therapy methods to treat Leber hereditary optic neuropathy in a mouse model.

Introduction: Therapies for Leber hereditary optic neuropathy (LHON), in common with all disorders caused by mutated mitochondrial DNA, are inadequate. We have developed two gene therapy strategies for the disease: mitochondrial-targeted and allotopic expressed and compared them in a mouse model of LHON.

Methods: A LHON mouse model was generated by intravitreal injection of a mitochondrialtargeted Adeno-associated virus (AAV) carrying mutant human NADH dehydrogenase 4 gene () to induce retinal ganglion cell (RGC) degeneration and axon loss, the hallmark of the human disease.

Using Noninvasive Electrophysiology to Determine Time Windows of Neuroprotection in Optic Neuropathies.

The goal of neuroprotection in optic neuropathies is to prevent loss of retinal ganglion cells (RGCs) and spare their function. The ideal time window for initiating neuroprotective treatments should be the preclinical period at which RGCs start losing their functional integrity before dying. Noninvasive electrophysiological tests such as the Pattern Electroretinogram (PERG) can assess the ability of RGCs to generate electrical signals under a protracted degenerative process in both clinical conditions and experimental models, which may have both diagnostic and prognostic values and provide the rationale for early treatment.

Gene therapy restores mitochondrial function and protects retinal ganglion cells in optic neuropathy induced by a mito-targeted mutant ND1 gene.

Therapies for genetic disorders caused by mutated mitochondrial DNA are an unmet need, in large part due barriers in delivering DNA to the organelle and the absence of relevant animal models. We injected into mouse eyes a mitochondrially targeted Adeno-Associated-Virus (MTS-AAV) to deliver the mutant human NADH ubiquinone oxidoreductase subunit I (hND1/m.3460 G > A) responsible for Leber's hereditary optic neuropathy, the most common primary mitochondrial genetic disease.

The Relationship Between Stage of Leber's Hereditary Optic Neuropathy and Pattern Electroretinogram Latency.

Purpose: The purpose of this study was to compare the baseline steady-state pattern electroretinogram (SS-PERG) of patients with G11778A Leber hereditary optic neuropathy (LHON) with different stages of visual acuity (VA) loss before allotopic gene therapy (GT).

Methods: Patients (n = 28) were enrolled into groups (GT I: chronic bilateral VA ≤35 Early Treatment Diabetic Retinopathy Study [ETDRS]; GT II: acute bilateral VA ≤35 ETDRS; GT III: acute unilateral, VA ≤35 ETDRS, and better eye VA ≥70 ETDRS) and tested with SS-PERG together with 210 age-matched normal controls (NCs). SS-PERG amplitude (nV) and latency (ms) of each eye were averaged for groups GT I, GT II, and NC.

Leber Hereditary Optic Neuropathy Gene Therapy: Adverse Events and Visual Acuity Results of All Patient Groups.

Purpose: To assess safety of gene therapy in G11778A Leber hereditary optic neuropathy (LHON).

Design: Phase 1 clinical trial.

Methods: Setting: single institution.

Retinal microvascular and neuronal function in patients with multiple sclerosis: 2-year follow-up.

Objective: To determine the longitudinal changes in retinal microstructure, microvasculature, microcirculation, and axonal and neuronal functions in patients with relapsing-remitting multiple sclerosis (RRMS) over the time course of about two years.

Methods: A total of 30 patients (60 eyes) with RRMS were followed for a period of 27 ± 6 months and evaluated with a battery of clinical tests including low contrast letter acuity (LCLA), intraretinal layer thicknesses by optical coherence tomography (OCT), ganglion cell function by steady-state pattern electroretinography (PERG), axonal function by polarization-sensitive OCT, volumetric vessel density (VVD) by OCT angiography, and retinal tissue perfusion (RTP) by retinal function imager.

Results: Axonal function measured as retinal nerve fiber layer birefringence in the temporal quadrant and vessel density in the deep vascular plexus were significantly decreased at 2-year follow-up (P < 0.

1α,25-dihydroxyvitamin D protects retinal ganglion cells in glaucomatous mice.

Background: Glaucoma is an optic neuropathy characterized by loss of function and death of retinal ganglion cells (RGCs), leading to irreversible vision loss. Neuroinflammation is recognized as one of the causes of glaucoma, and currently no treatment is addressing this mechanism. We aimed to investigate the anti-inflammatory and neuroprotective effects of 1,25(OH)D (1α,25-dihydroxyvitamin D, calcitriol), in a genetic model of age-related glaucomatous neurodegeneration (DBA/2J mice).

Diabetes Exacerbates the Intraocular Pressure-Independent Retinal Ganglion Cells Degeneration in the DBA/2J Model of Glaucoma.

Purpose: Glaucoma is a multifactorial disease, causing retinal ganglion cells (RGCs) and optic nerve degeneration. The role of diabetes as a risk factor for glaucoma has been postulated but still not unequivocally demonstrated. The purpose of this study is to clarify the effect of diabetes in the early progression of glaucomatous RGC dysfunction preceding intraocular pressure (IOP) elevation, using the DBA/2J mouse (D2) model of glaucoma.

Modeling Retinal Ganglion Cell Dysfunction in Optic Neuropathies.

As in glaucoma and other optic neuropathies cellular dysfunction often precedes cell death, the assessment of retinal ganglion cell (RGC) function represents a key outcome measure for neuroprotective strategies aimed at targeting distressed but still viable cells. RGC dysfunction can be assessed with the pattern electroretinogram (PERG), a sensitive measure of electrical activity of RGCs that is recorded non-invasively in human subjects and mouse models. Here, we offer a conceptual framework based on an intuitive state-transition model used for disease management in patients to identify progressive, potentially reversible stages of RGC dysfunction leading to cell death in mouse models of glaucoma and other optic neuropathies.

Retinal and cortical visual acuity in a common inbred albino mouse.

While albino mice are widely used in research which includes the use of visually guided behavioral tests, information on their visual capability is scarce. We compared the spatial resolution (acuity) of albino mice (BALB/c) with that of pigmented mice (C57BL/6J). We used a high-throughput pattern electroretinogram (PERG) and pattern visual evoked potential (PVEP) method for objective assessment of retinal and cortical acuity, as well as optomotor head-tracking response/ reflex (OMR).

Compartmental Differences in Macular Retinal Ganglion Cell Function.

Purpose: The purpose of this study was to investigate local differences of macular retinal ganglion cell (RGC) function by means of the steady-state pattern electroretinogram (SS-PERG).

Methods: SS-PERGs were recorded in healthy subjects (n = 43) in response to gratings (1.6 c/deg, 15.

P2X7 receptor antagonism preserves retinal ganglion cells in glaucomatous mice.

To investigate the role of P2X7 receptor to preserve retinal ganglion cells (RGCs) structure and function in a genetic mouse model (DBA/2J mouse) of age-related glaucomatous neurodegeneration. Chronic treatment with P2X7 receptor antagonist eye drops was carried out in order to assess RGCs function and density by pattern electroretinogram (PERG) and RBPMS immunostaining, respectively. Further, microglia activation was assessed in flat-mounted retina by using Iba-1 immunostaining.

Nicotinamide-Rich Diet in DBA/2J Mice Preserves Retinal Ganglion Cell Metabolic Function as Assessed by PERG Adaptation to Flicker.

Flickering light increases metabolic demand in the inner retina. Flicker may exacerbate defective mitochondrial function in glaucoma, which will be reflected in the pattern electroretinogram (PERG), a sensitive test of retinal ganglion cell (RGC) function. We tested whether flicker altered the PERG of DBA/2J (D2) glaucomatous mice and whether vitamin B3-rich diet contributed to the flicker effect.

Non-invasive Assessment of Central Retinal Artery Pressure: Age and Posture-dependent Changes.

: Assessment of Ocular Perfusion Pressure (OPP) requires estimation of the Mean Central Retinal Artery Pressure (MCRAP) [OPP = MCRAP-IOP]. In a seated position, MCRAP is currently estimated as 2/3 of the Mean Arterial Pressure (MAP) to account for the hydrostatic reduction of MAP at eye level. We tested a surrogate method for direct MCRAP assessment by measuring MAP with Arm-Up and cuff at eye level (AUMAP) at different postures and ages.