Pharmacological Activation and Transgenic Overexpression of SIRT1 Attenuate Traumatic Optic Neuropathy Induced by Blunt Head Impact.

Purpose: Resveratrol (RSV) is a nutraceutical compound known for its therapeutic potential in neurodegenerative and metabolic diseases. RSV promotes survival signals in retinal ganglion cells (RGCs) through activation of SIRT1, an NAD+-dependent deacetylase. RSV and SIRT1 reduce RGC loss induced by direct optic nerve injury, but effects in indirect models of traumatic optic neuropathy remain unknown and are examined in this study.

Comparison of Brn3a and RBPMS Labeling to Assess Retinal Ganglion Cell Loss During Aging and in a Model of Optic Neuropathy.

Purpose: Retinal ganglion cell (RGC) loss provides the basis for diagnosis and stage determination of many optic neuropathies, and quantification of RGC survival is a critical outcome measure in models of optic neuropathy. This study examines the accuracy of manual RGC counting using two selective markers, Brn3a and RBPMS.

Methods: Retinal flat mounts from 1- to 18-month-old C57BL/6 mice, and from mice after microbead (MB)-induced intraocular pressure (IOP) elevation, are immunostained with Brn3a and/or RBPMS antibodies.

A multi-cohort genome-wide association study in African ancestry individuals reveals risk loci for primary open-angle glaucoma.

Primary open-angle glaucoma (POAG), the leading cause of irreversible blindness worldwide, disproportionately affects individuals of African ancestry. We conducted a genome-wide association study (GWAS) for POAG in 11,275 individuals of African ancestry (6,003 cases; 5,272 controls). We detected 46 risk loci associated with POAG at genome-wide significance.

AAV2 vector optimization for retinal ganglion cell-targeted delivery of therapeutic genes.

Recombinant adeno-associated virus (AAV)-2 has significant potential as a delivery vehicle of therapeutic genes to retinal ganglion cells (RGCs), which are key interventional targets in optic neuropathies. Here we show that when injected intravitreally, AAV2 engineered with a reporter gene driven by cytomegalovirus (CMV) enhancer and chicken β-actin (CBA) promoters, displays ubiquitous and high RGC expression, similar to its synthetic derivative AAV8BP2. A novel AAV2 vector combining the promoter of the human RGC-selective γ-synuclein (hSNCG) gene and woodchuck hepatitis post-transcriptional regulatory element (WPRE) inserted upstream and downstream of a reporter gene, respectively, induces widespread transduction and strong transgene expression in RGCs.

The Retinal Ganglion Cell Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration Consortium.

Purpose: The Retinal Ganglion Cell (RGC) Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration (RReSTORe) consortium was founded in 2021 to help address the numerous scientific and clinical obstacles that impede development of vision-restorative treatments for patients with optic neuropathies. The goals of the RReSTORe consortium are: (1) to define and prioritize the most critical challenges and questions related to RGC regeneration; (2) to brainstorm innovative tools and experimental approaches to meet these challenges; and (3) to foster opportunities for collaborative scientific research among diverse investigators.

Design And Participants: The RReSTORe consortium currently includes > 220 members spanning all career stages worldwide and is directed by an organizing committee comprised of 15 leading scientists and physician-scientists of diverse backgrounds.

Emerging Gene Therapy Technologies for Retinal Ganglion Cell Neuroprotection.

Optic neuropathies encompass a breadth of diseases that ultimately result in dysfunction and/or loss of retinal ganglion cells (RGCs). Although visual impairment from optic neuropathies is common, there is a lack of effective clinical treatments. Addressing a critical need for novel interventions, preclinical studies have been generating a growing body of evidence that identify promising new drug-based and cell-based therapies.

Risk factors for structural and functional progression of primary open-angle glaucoma in an African ancestry cohort.

Background/aims: To investigate the rates of structural and functional progression of primary open-angle glaucoma in an African ancestry cohort and identify risk factors for progression.

Methods: This retrospective study included 1424 eyes from glaucoma cases in the Primary Open-Angle African American Glaucoma Genetics cohort, with ≥2 visits for retinal nerve fibre layer (RNFL) thickness and mean deviation (MD) measurements over ≥6-month follow-up. The rates of structural progression (change in RNFL thickness/year) and functional progression (change in MD/year) were calculated from linear mixed effects models, accounting for intereye correlation and longitudinal correlation.

Cell-Specific Expression of Human SIRT1 by Gene Therapy Reduces Retinal Ganglion Cell Loss Induced by Elevated Intraocular Pressure.

SIRT1 prevents retinal ganglion cell (RGC) loss in several acute and subacute optic neuropathy models following pharmacologic activation or genetic overexpression. We hypothesized that adeno-associated virus (AAV)-mediated overexpression of SIRT1 in RGCs in a chronic ocular hypertension model can reduce RGC loss, thereby preserving visual function by sustained therapeutic effect. A control vector AAV-eGFP and therapeutic vector AAV-SIRT1 were constructed and optimized for transduction efficiency.

Recruitment strategies and lessons learned from a large genetic study of African Americans.

Genetic studies must enroll large numbers of participants to obtain adequate statistical power. Data are needed on how researchers can best use limited financial and practical resources to achieve these targets, especially in under-represented populations. This paper provides a retrospective analysis of the recruitment strategies for a large glaucoma genetics study in African Americans.

Frequency and Etiologies of Visual Disturbance After Cataract Surgery Identified in Neuro-Ophthalmology Clinics.

Background: To identify the frequency and etiologies of visual disturbances after cataract surgery in patients referred to Neuro-ophthalmology.

Methods: This study is a retrospective chart review. Records of patients 18 years and older referred to neuro-ophthalmology clinics for new-onset visual disturbances within 6 months of cataract surgery were reviewed.

Repeat Brn3a immunolabeling rescues faded staining and improves detection of retinal ganglion cells.

Immunofluorescence is used in numerous research areas including eye research to detect specific antigens in cells and tissues. One limitation is that fluorescent signal can fade, causing detection problems if data recording was not completed in a timely manner or if additional data acquisition is required. The ability to repeat immunostaining for the same antigen after initial fluorescence has faded may require time-consuming and potentially damaging steps to remove primary antibodies.

Resolution of COVID-19 induced anosmia following treatment with ST266.

Background: Persistent anosmia following COVID-19 disease affects a significant subset of patients. Symptoms of this olfactory dysfunction negatively impact patient quality of life, and effective treatments are lacking; therefore, novel therapies that restore the ability to smell have tremendous clinical potential.

Case Report: A 46-year-old female enrolled in a phase I clinical trial to assess the safety of targeted intranasal administration of a novel acellular secretome therapy (ST266) in patients diagnosed as glaucoma suspects.

The Importance of Health Literacy in Addressing Eye Health and Eye Care Disparities.

Disparities in eye health and eye care frequently result from a lack of understanding of ocular diseases and limited use of ophthalmic health services by various populations. The purpose of this article is to describe the principle of health literacy and its central role in enhancing health, and how its absence can result in poorer health outcomes. The article evaluates the current status of health literacy in visual health and disparities that exist among populations.

Selective Upregulation of SIRT1 Expression in Retinal Ganglion Cells by AAV-Mediated Gene Delivery Increases Neuronal Cell Survival and Alleviates Axon Demyelination Associated with Optic Neuritis.

Optic neuritis (ON), the most common ocular manifestation of multiple sclerosis, is an autoimmune inflammatory demyelinating disease also characterized by degeneration of retinal ganglion cells (RGCs) and their axons, which commonly leads to visual impairment despite attempted treatments. Although ON disease etiology is not known, changes in the redox system and exacerbated optic nerve inflammation play a major role in the pathogenesis of the disease. Silent information regulator 1 (sirtuin-1/SIRT1) is a ubiquitously expressed NAD-dependent deacetylase, which functions to reduce/prevent both oxidative stress and inflammation in various tissues.

-Associated Neurodegeneration: A Case Report Highlights Possible Mechanisms of Normal Tension Glaucoma.

is one of a number of genes implicated in the pathogenesis of adult-onset primary open angle glaucoma (POAG). Here we describe in detail the phenotype of a patient with pathogenic variation in who presented with a protracted history of central vision loss. On exam visual acuities were at 20/100 level, had a tritan color defect and showed central arcuate visual field defects on visual field testing.

Socioeconomic and Geographic Disparities in Idiopathic Intracranial Hypertension.

Objective: To identify relationships between idiopathic intracranial hypertension (IIH) and socioeconomic determinants of health, such as low-income status and proximity to healthy food.

Methods: This retrospective case-control study of adult female neuro-ophthalmology patients from one institution identified 223 women with and 4,783 women without IIH. Street addresses were geocoded and merged with US census data to obtain census tract-level information on income and food access.

Rescue of retinal ganglion cells in optic nerve injury using cell-selective AAV mediated delivery of SIRT1.

SIRT1 prevents retinal ganglion cell (RGC) loss in models of optic neuropathy following pharmacologic activation or genetic overexpression. The exact mechanism of loss is not known, prior evidence suggests this is through oxidative stress to either neighboring cells or RGC specifically. We investigated the neuroprotective potential of RGC-selective SIRT1 gene therapy in the optic nerve crush (ONC) model.

RGC and Vision Loss From Traumatic Optic Neuropathy Induced by Repetitive Closed Head Trauma Is Dependent on Timing and Force of Impact.

Purpose: Traumatic optic neuropathy (TON) is often caused by blunt head trauma and has no currently effective treatment. Common animal models of TON induced by surgical crush injury are plagued by variability and do not mimic typical mechanisms of TON injury. Traumatic head impact models have recently shown evidence of TON, but the degree of head impact necessary to consistently induce TON is not well characterized, and it is examined here.

The sensitivity and specificity of retinal and choroidal folds to distinguish between mild papilloedema and pseudopapilledema.

Purpose: To determine if the presence or absence of retinal and choroidal folds on SD-OCT imaging can distinguish between mild papilloedema and pseudopapilledema.

Design: Cross-sectional cohort study METHODS: Subjects with optic disc elevation (Frisen grades 1 and 2 only) were eligible to be enrolled prospectively. Pseudopapilledema was defined as a lack of change in optic disc appearance between two visits <6 months apart, and papilloedema was defined as change in optic disc appearance between two visits <6 months apart determined by review of fundus photographs by a masked neuro-ophthalmologist.

Role of Ocular Ultrasonography to Distinguish Papilledema From Pseudopapilledema.

Background: We prospectively evaluated the sensitivity and specificity of ocular ultrasonography (OUS) to distinguish papilledema from pseudopapilledema.

Methods: Forty-nine study participants, with optic disc elevation, underwent neuro-ophthalmic evaluation, OUS, fundus photography, and optical coherence tomography (OCT) of the optic nerve head at the initial and follow-up visits (≤6 months apart). Participants were classified as having papilledema if there was a change in optic nerve appearance on fundus photographs, as determined by a masked observer, between initial and follow-up visits ≤6 months apart.