Retinal ganglion cell

PURPOSE: To establish an inducible model of retinal ischemia/reperfusion injury (RI/RI) in nonhuman primates (NHPs) to improve our understanding of the disease conditions and evaluate treatment interventions in humans. METHODS: We cannulated the right eye of rhesus macaques with a needle attached to a normal saline solution reservoir at up to 1.9 m above the eye level that resulted in high intraocular pressure of over 100 mm Hg for 90 minutes. Retinal morphology and function were monitored before and after RI/RI over two months by fundus photography, optical coherence tomography, electroretinography, and visual evoked potential...

BACKGROUND: Alterations of the superficial retinal vasculature are commonly observed in multiple sclerosis (MS) and can be visualized through optical coherence tomography angiography (OCTA). OBJECTIVES: This study aimed to examine changes in the retinal vasculature during MS and to integrate findings into current concepts of the underlying pathology. METHODS: In this cross-sectional study, including 259 relapsing-remitting MS patients and 78 healthy controls, we analyzed OCTAs using deep-learning-based segmentation algorithm tools...

Optic nerve injuries are severely disrupt the structural and functional integrity of the retina, often leading to visual impairment or blindness. Despite the profound impact of these injuries, the molecular mechanisms involved remain poorly understood. In this study, we performed a comprehensive whole-transcriptome analysis of mouse retina samples after optic nerve crush (ONC) to elucidate changes in gene expression and regulatory networks. Transcriptome analysis revealed a variety of molecular alterations, including 256 mRNAs, 530 lncRNAs, and 37 miRNAs, associated with metabolic, inflammatory, signaling, and biosynthetic pathways in the injured retina...

Fibulin-3 (FBLN3, aka EFEMP1) is a secreted extracellular matrix (ECM) glycoprotein implicated in ocular diseases including glaucoma and age-related macular degeneration. Yet surprisingly, little is known about its native biology, expression patterns, and localization in the eye. To overcome these shortcomings, we conducted gene expression and immunohistochemistry for FBLN3 in ocular tissue from mice, pigs, non-human primates, and humans. Moreover, we evaluated age-related changes in FBLN3 and FBLN3-related ECM remodeling enzymes/inhibitors in aging mice...

UNLABELLED: Many inherited retinal diseases target photoreceptors, which transduce light into a neural signal that is processed by the downstream visual system. As photoreceptors degenerate, physiological and morphological changes to retinal synapses and circuitry reduce sensitivity and increase noise, degrading visual signal fidelity. Here, we pharmacologically targeted the first synapse in the retina in an effort to reduce circuit noise without sacrificing visual sensitivity. We tested a strategy to partially replace the neurotransmitter lost when photoreceptors die with an agonist of receptors that ON bipolars cells use to detect glutamate released from photoreceptors...

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PURPOSE: To assess the diagnostic performance and structure-function association of retinal retardance (RR), a customized metric measured by a prototype polarization-sensitive optical coherence tomography (PS-OCT), across various stages of glaucoma. METHODS: This cross-sectional pilot study analyzed 170 eyes from 49 healthy individuals and 68 patients with glaucoma. The patients underwent PS-OCT imaging and conventional spectral-domain optical coherence tomography (SD-OCT), as well as visual field (VF) tests...

BACKGROUND: While retinal vessel changes are evident in the eyes of patients with relapsing-remitting multiple sclerosis (RRMS), changes in the vasculature of possible MS mimics such as primary Sjögren's syndrome (pSS) remain to be determined. We investigated the potential of retinal optical coherence tomography (OCT) angiography (OCTA) as diagnostic tool to differentiate between patients with RRMS and pSS. METHODS: This cross-sectional study included patients with RRMS (n = 36), pSS (n = 36) and healthy controls (n = 30)...

C1q/TNF-related protein-9 (CTRP9) has been reported to play roles in several types of retinal diseases. However, the role and the potential mechanism of CTRP9 in glaucoma are still incompletely understood. The expression of CTRP9 in OGD/R-induced retinal ganglion cells (RGCs) was detected by quantitative real-time polymerase chain reaction and western blot assay. Cell proliferation was identified by cell counting Kit-8 assay. Flow cytometry, enzyme-linked immunosorbent assay and western blot assay were performed to assess cell apoptosis...

BACKGROUND: Retinal ischemia/reperfusion (RIR) is implicated in various forms of optic neuropathies, yet effective treatments are lacking. RIR leads to the death of retinal ganglion cells (RGCs) and subsequent vision loss, posing detrimental effects on both physical and mental health. Apigenin (API), derived from a wide range of sources, has been reported to exert protective effects against ischemia/reperfusion injuries in various organs, such as the brain, kidney, myocardium, and liver...

PURPOSE: This study aimed to evaluate the ocular characteristics associated with spontaneously high myopia in adult nonhuman primates (NHPs). METHODS: A total of 537 eyes of 277 macaques with an average age of 18.53 ± 3.01 years (range = 5-26 years), raised in a controlled environment, were included. We measured ocular parameters, including spherical equivalent (SE), axial length (AXL), and intraocular pressure. The 45-degree fundus images centered on the macula and the disc assessed the fundus tessellation and parapapillary atrophy (PPA)...

Glaucoma, the leading cause of irreversible blindness worldwide, is characterized by neurodegeneration and neuroinflammation with retinal NAD/NADP and GSH decline. Nicotinamide adenine dinucleotide (NAD)/NAD phosphate (NADP) and glutathione (GSH) are two redox reducers in neuronal and glial metabolism. However, therapeutic strategies targeting NAD/NADP or GSH do not exert ideal effects, and the underlying mechanisms are still poorly understood. We assessed morphological changes in retinal ganglion cells (RGCs), the affected neurons in glaucoma, and Müller cells, the major glial cells in the retina, as well as the levels of phosphorylated p38 (p-p38) and Caspase-3 in glaucoma patients...

The vasculature of the central nervous system is a 3D lattice composed of laminar vascular beds interconnected by penetrating vessels. The mechanisms controlling 3D lattice network formation remain largely unknown. Combining viral labeling, genetic marking, and single-cell profiling in the mouse retina, we discovered a perivascular neuronal subset, annotated as Fam19a4/Nts-positive retinal ganglion cells (Fam19a4/Nts-RGCs), directly contacting the vasculature with perisomatic endfeet. Developmental ablation of Fam19a4/Nts-RGCs led to disoriented growth of penetrating vessels near the ganglion cell layer (GCL), leading to a disorganized 3D vascular lattice...

Alterations in intraocular and external pressure critically involve the pathogenesis of glaucoma, traumatic retinal injury (TRI), and other retinal disorders, and retinal neurons have been reported to express multiple mechanical-sensitive channels (MSCs) in recent decades. However, the role of MSCs in visual functions and pressure-related retinal conditions has been unclear. This review will focus on the variety and functional significance of the MSCs permeable to K+ , Na+ , and Ca2+ , primarily including the big potassium channel (BK); the two-pore domain potassium channels TRAAK and TREK; Piezo; the epithelial sodium channel (ENaC); and the transient receptor potential channels vanilloid TRPV1, TRPV2, and TRPV4 in retinal photoreceptors, bipolar cells, horizontal cells, amacrine cells, and ganglion cells...

The axons of retinal ganglion cells (RGCs) form the optic nerve, transmitting visual information from the eye to the brain. Damage or loss of RGCs and their axons is the leading cause of visual functional defects in traumatic injury and degenerative diseases such as glaucoma. However, there are no effective clinical treatments for nerve damage in these neurodegenerative diseases. Here, we report that LIM homeodomain transcription factor Lhx2 promotes RGC survival and axon regeneration in multiple animal models mimicking glaucoma disease...

Glaucoma is a heterogeneous group of optic neuropathies characterized by a progressive degeneration of the retinal ganglion cells (RGCs), leading to irreversible vision loss. Nowadays, the traditional therapeutic approach to glaucoma consists of lowering the intraocular pressure (IOP), which does not address the neurodegenerative features of the disease. Besides animal models of glaucoma, there is a considerable need for in vitro experimental models to propose new therapeutic strategies for this ocular disease...

Ca2+ /calmodulin-dependent protein kinase II (CaMKII) is a family of broad substrate specificity serine (Ser)/threonine (Thr) protein kinases that play a crucial role in the Ca2+ -dependent signaling pathways. Its significance as an intracellular Ca2+ sensor has garnered abundant research interest in the domain of neurodegeneration. Accumulating evidences suggest that CaMKII is implicated in the pathology of degenerative retinopathies such as diabetic retinopathy (DR), age-related macular degeneration (AMD), retinitis pigmentosa (RP) and glaucoma optic neuropathy...

OBJECTIVE: Excessive dietary sodium intake has known adverse effects on intravascular fluid volume and systemic blood pressure, which may influence intraocular pressure (IOP) and glaucoma risk. This study aimed to assess the association of urinary sodium excretion, a biomarker of dietary intake, with glaucoma and related traits, and to determine whether this relationship is modified by genetic susceptibility to disease. DESIGN: Cross-sectional observational and gene-environment interaction analyses in the population-based UK Biobank study...

Retinal prosthetics are one of the leading therapeutic strategies to restore lost vision in patients with Retinitis Pigmentosa and age-related macular degeneration. Much work has described patterns of spiking in retinal ganglion cells (RGCs) in response to electrical stimulation, but less work has examined the underlying retinal circuitry that is activated by electrical stimulation to drive these responses. Surprisingly, little is known about the role of inhibition in generating electrical responses, or how inhibition might be altered during degeneration...

PURPOSE: Mutations in the genes encoding type IV collagen alpha 1 (COL4A1) and alpha 2 (COL4A2) cause a multisystem disorder that includes ocular anterior segment dysgenesis (ASD) and glaucoma. We previously showed that transforming growth factor beta (TGFβ) signaling was elevated in developing anterior segments from Col4a1 mutant mice and that reducing TGFβ signaling ameliorated ASD, supporting a role for the TGFβ pathway in disease pathogenesis. Here, we tested whether altered TGFβ signaling also contributes to glaucoma-related phenotypes in Col4a1 mutant mice...