IL-6 amplifies corneal transplant alloimmunity by inducing dysfunctional IFN-γ- secreting Treg through the VEGFA-VEGFR1 axis.

Background: Corneal allografts generally exhibit high acceptance due to the immune-privileged ocular microenvironment. Regulatory T cells (Treg) promote graft tolerance; however, in a vascularized milieu, they may acquire a pro-inflammatory phenotype. We investigated how dysfunctional Treg contribute to graft rejection through the VEGFA-VEGFR1 axis.

Optimizing tissue clearing methods for improved imaging of whole-mount retinas and optic nerves.

Background: Gene and cell therapies hold promise for restoring vision in hereditary and advanced optic neuropathies. Accurate evaluation of these therapies requires advanced imaging methods that can visualize transplanted cells within intact retinal tissue.

New Method: We present a whole-mount tissue-clearing workflow optimized for the mouse retina and optic nerve to improve visualization of donor neuron integration following cell transplantation.

Deep Learning with Disc Photos or OCT Scans in Glaucoma Detection.

Objective: To determine whether a deep learning (DL) model using retinal nerve fiber layer thickness (RNFLT) maps from OCT scans can detect glaucoma, defined by functional visual field (VF) impairment, more accurately than a DL model using disc photos (DPs). A secondary objective was to assess the diagnostic performance of these DL models across demographic groups (race, sex, and ethnicity).

Design: Retrospective cohort study at a tertiary glaucoma center utilizing OCT and DP datasets collected between 2011 and 2022.

The Mechanism of PMC (2,2,5,7,8-Pentamethyl-6-chromanol), a Sterically Hindered Phenol Antioxidant, in Rescuing Oxidized Low-Density-Lipoprotein-Induced Cytotoxicity in Human Retinal Pigment Epithelial Cells.

Geographic atrophy or late-stage dry age-related macular degeneration (AMD) is characterized by drusen deposition and progressive retinal pigment epithelium (RPE) degeneration, leading to irreversible vision loss. The formation of drusen leads to dyshomeostasis, oxidative stress, and irreversible damage to the RPE. In this study, we used an in vitro model of oxidized low-density lipoprotein (ox-LDL)-induced human RPE damage/death to investigate the mechanism through which a sterically hindered phenol antioxidant compound, PMC (2,2,5,7,8-pentamethyl-6-chromanol), protects the RPE against ox-LDL-induced damage.

Use Challenges and Training Needs of In-Vehicle Technologies for Older Drivers With Vision Impairments.

Importance: Older drivers with impaired vision may face challenges using in-vehicle technologies, affecting user experience.

Objective: To explore use challenges with in-vehicle technologies and training preferences of older drivers with and without central vision loss (CVL).

Design: A telephone questionnaire on perceptions of driver-vehicle interface use difficulties, challenges with existing advanced driver assistance systems (ADAS), and preferences for ADAS acquisition and training.

Type 2 Diabetes-Associated Phenylacetylglutamine Induces Deleterious Inflammation Cycle in Myeloid Cells through β Adrenergic Receptors and Impedes Wound Healing.

Despite advances in glucose-lowering therapies, many diabetic patients still suffer inflammation-related complications such as chronic non-healing wounds. The microbiota-derived metabolite phenylacetylglutamine (PAGln) is identified as a causal driver of these wounds via a transmissible, β-adrenergic receptor-mediated trained-immunity loop. Metabolomics reveals PAGln is elevated in type 2 diabetes and tightly associated with poor healing in both diabetic and non-diabetic human patients.

Are directional or non-directional hazard warnings more helpful for drivers with homonymous visual field loss?

People with homonymous visual field loss (HVFL), the loss of vision in the same half of the visual field in both eyes, are permitted to drive in some jurisdictions. However, the HVFL may cause delayed responses to hazards from the side of their vision loss (blind side). Warnings that indicate hazard direction may be beneficial.

Adrenergic signaling coordinates distant and local responses to amputation in axolotl.

Many species regenerate lost body parts following amputation. Most limb regeneration research has focused on the immediate injury site. Meanwhile, body-wide injury responses remain largely unexplored but may be critical for regeneration.

An Ex Vivo Explant Model for Studying Glial Interactions in the Mouse Retina.

The role of glia in glaucoma is an increasingly prominent research topic, but much remains unknown about how populations of these support cells - namely astrocytes and microglia - influence retinal ganglion cell survival. While in vivo and in vitro models provide a degree of insight, both approaches have significant limitations, such as the impact of peripheral immune response in the former and changes to physiological function induced by cell isolation and culture in the case of the latter. To minimize these confounding factors, we have developed an ex vivo retinal explant system in which astrocytes, microglia, and other retinal cell types can be maintained in situ for periods of at least 3 days, enabling targeted investigation at a higher throughput than is typically feasible with in vivo models.

Metabolic stress and early cell death in photoreceptor precursor cells following retinal transplantation.

Background: Progressive photoreceptor loss in retinal degenerative diseases leads to irreversible vision impairment. Transplantation of human embryonic or induced pluripotent stem cell-derived photoreceptor precursor cells (PRPCs) offers potential for vision restoration. However, substantial early donor cell loss remains a major challenge.

Equity-enhanced glaucoma progression prediction from OCT with knowledge distillation.

Glaucoma is a progressive disease that can lead to permanent vision loss, making progression prediction vital for guiding effective treatment. Deep learning aids progression prediction but may yield unequal outcomes across demographic groups. We proposed a model called FairDist, which utilized baseline optical coherence tomography scans to predict glaucoma progression.

Naturally derived mucoadhesive nanosuspension for treatment of multiple staged ocular infections.

Bacterial ocular infections pose significant risks to vision and incur substantial economic burdens worldwide. Current standards of care, such as eye drops and ointments, suffer from poor drug bioavailability (<5 %), rapid clearance, and insufficient retention, preventing dual prophylactic and therapeutic efficacy. To address these limitations, we developed naturally derived mucoadhesive gelatin methacryloyl (GelMA) nanoparticles (NPs) functionalized with phenylboronic acid (PBA), named GelMAP, for the sustained delivery of moxifloxacin (MFX), a broad-spectrum antibacterial agent.

Treatment of nitrogen mustard-induced corneal injury with alpha-melanocyte stimulating hormone.

Nitrogen mustard (NM) exposure leads to severe corneal damage, resulting in persistent corneal inflammation, epithelial damage, endothelial dysfunction, and vision impairment. Effective therapeutic strategies to mitigate these effects remain limited. This study evaluates the protective effects of alpha-melanocyte-stimulating hormone (α-MSH) in a murine model of NM-induced corneal injury.

Directional vibro-tactile hazard warnings for drivers with vision impairments.

Vision impairment may delay responses to hazards when driving. In a proof-of-concept driving simulator study, we evaluated a hazard warning device designed for vision impaired drivers. Three groups participated: 11 persons with central vision loss (CVL; median age 60 years), 12 with homonymous field loss (HFL; 52 years) and 11 with normal vision (NV; 60 years).

Equitable Deep Learning for Diabetic Retinopathy Detection Using Multidimensional Retinal Imaging With Fair Adaptive Scaling.

Purpose: To investigate the fairness of existing deep models for diabetic retinopathy (DR) detection and introduce an equitable model to reduce group performance disparities.

Methods: We evaluated the performance and fairness of various deep learning models for DR detection using fundus images and optical coherence tomography (OCT) B-scans. A Fair Adaptive Scaling (FAS) module was developed to reduce group disparities.

DNA Methylation Dynamics in a Mouse Model of Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is a group of sight-threatening genetic diseases characterized by progressive degeneration of photoreceptors, leading to severe vision loss from childhood to adulthood. With limited treatment options, understanding the molecular mechanisms underlying RP is crucial. Increased DNA methylation, especially in degenerating photoreceptors, is a contributing factor to retinal damage in RP.

Single-cell transcriptome of retinal myeloid cells in response to transplantation of human neurons reveals reversibility of microglial activation.

The host retinal microglia and macrophage activation remains a major challenge for the integration of donor neurons following transplantation. Previously, we and others have shown that it is possible to increase donor retinal ganglion cell (RGC) survival by inhibiting the microglia-RGC interaction with Annexin V or through reprogramming microglia with the soluble Fas ligand. However, the exact mechanisms of the microglia/macrophage activation and their heterogeneity following transplantation remain unknown.

Deep learning model for differentiating thyroid eye disease and orbital myositis on computed tomography (CT) imaging.

Purpose: To develop a deep learning model using orbital computed tomography (CT) imaging to accurately distinguish thyroid eye disease (TED) and orbital myositis, two conditions with overlapping clinical presentations.

Methods: Retrospective, single-center cohort study spanning 12 years including normal controls, TED, and orbital myositis patients with orbital imaging and examination by an oculoplastic surgeon. A deep learning model employing a Visual Geometry Group-16 network was trained on various binary combinations of TED, orbital myositis, and controls using single slices of coronal orbital CT images.

Mucoadhesive micellar eyedrops for the treatment of ocular inflammation.

Efficient ocular drug delivery remains a significant challenge in treating eye inflammation due to physiological barriers such as the tear film and frequent blinking, which lead to rapid drug clearance. Commercial eyedrops, like Oceanside® (0.5 % loteprednol etabonate (LE) ophthalmic suspension), suffer from low ocular bioavailability and require frequent dosing to maintain therapeutic levels.

Macrophages Transdifferentiate Into Myofibroblasts During Ocular Surface Inflammation.

Ocular surface inflammation and injury often lead to fibrosis and impaired vision. Myofibroblasts directly promote fibrosis by producing excessive extracellular matrix (ECM) proteins and alpha-smooth muscle actin (ɑ-SMA). In addition, macrophages have been shown to promote fibrosis by secreting pro-fibrotic factors to stimulate myofibroblast formation.

An Artificial Intelligence Method for Phenotyping of OCT-Derived Thickness Maps Using Unsupervised and Self-supervised Deep Learning.

The objective of this study is to enhance the understanding of ophthalmic disease physiology and genetic architecture through the analysis of optical coherence tomography (OCT) images using artificial intelligence (AI). We introduce a novel AI methodology that addresses the challenge of transferring OCT phenotypes across datasets. The approach employs unsupervised and self-supervised learning techniques to phenotype and cluster OCT-derived retinal layer thicknesses, using glaucoma as a model disease.