MicroRNA profile of extracellular vesicles released by Müller glial cells.

Introduction: As with any other radial glia in the central nervous system, Müller glia derive from the same neuroepithelial precursors, perform similar functions, and exhibit neurogenic properties as radial glia in the brain. Müller glial cells retain progenitor-like characteristics in the adult human eye and can partially restore visual function upon intravitreal transplantation into animal models of glaucoma. Recently, it has been demonstrated that intracellular communication is possible via the secretion of nano-sized membrane-bound extracellular vesicles (EV), which contain bioactive molecules like microRNA (miRNA) and proteins that induce phenotypic changes when internalised by recipient cells.

Cell-Based Therapies for Glaucoma.

Glaucomatous optic neuropathy (GON) is the major cause of irreversible visual loss worldwide and can result from a range of disease etiologies. The defining features of GON are retinal ganglion cell (RGC) degeneration and characteristic cupping of the optic nerve head (ONH) due to tissue remodeling, while intraocular pressure remains the only modifiable GON risk factor currently targeted by approved clinical treatment strategies. Efforts to understand the mechanisms that allow species such as the zebrafish to regenerate their retinal cells have greatly increased our understanding of regenerative signaling pathways.

Transcriptomics of CD29/CD44 cells isolated from hPSC retinal organoids reveals a single cell population with retinal progenitor and Müller glia characteristics.

Müller glia play very important and diverse roles in retinal homeostasis and disease. Although much is known of the physiological and morphological properties of mammalian Müller glia, there is still the need to further understand the profile of these cells during human retinal development. Using human embryonic stem cell-derived retinal organoids, we investigated the transcriptomic profiles of CD29/CD44 cells isolated from early and late stages of organoid development.

Prospects for the application of Müller glia and their derivatives in retinal regenerative therapies.

Neural cell death is the main feature of all retinal degenerative disorders that lead to blindness. Despite therapeutic advances, progression of retinal disease cannot always be prevented, and once neuronal cell damage occurs, visual loss cannot be reversed. Recent research in the stem cell field, and the identification of Müller glia with stem cell characteristics in the human eye, have provided hope for the use of these cells in retinal therapies to restore vision.

Strain Specific Responses in a Microbead Rat Model of Experimental Glaucoma.

Purpose: A major challenge in glaucoma research is the lack of reproducible animal models of RGC and optic nerve damage, the characteristic features of this condition. We therefore examined the glaucomatous responses of two different rat strains, the Brown Norway (BN) and Lister Hooded (LH) rats, to high intraocular pressure (IOP) induced by injection of magnetic beads into the anterior chamber.

Methods: Magnetic microsphere suspensions (20 µl of 5-20 mg/ml) were injected into the anterior chamber of BN (n = 9) or LH (N = 15) rats.

Galectins and their involvement in ocular disease and development.

Galectins are carbohydrate binding proteins with high affinity to ß-galactoside containing glycoconjugates. Understanding of the functions of galectins has grown steadily over the past decade, as a result of substantial advancements in the field of glycobiology. Galectins have been shown to be versatile molecules that participate in a range of important biological systems, including inflammation, neovascularisation and fibrosis.

Insights into the design of spray systems for cell therapies for retinal disease using computational modelling.

Chronic eye diseases are the main cause of vision loss among adults. Among these, retinal degenerative diseases affect millions of people globally, causing permanent loss of cells and organ dysfunction. Despite recent progress in developing stem cell therapies for retinal diseases, methods for delivery remain an area of intense research.

Potential of Müller Glia for Retina Neuroprotection.

Müller glia constitute the main glial cells of the retina. They are spatially distributed along this tissue, facilitating their close membrane interactions with all retinal neurons. Müller glia are characterized by their active metabolic functions, which are neuroprotective in nature.

Physical Punishment and Child Externalizing Behavior: Comparing American Indian, White, and African American Children.

This study examined if, compared to White and African American children, maternal spanking of American Indian children was associated with child externalizing behavior problems. Using a community-based sample of 3,632 children (1,183 White, 2,183 African American, 266 American Indian), multiple-group autoregressive cross-lagged models examined the associations between maternal spanking and child externalizing behavior across the first 5 years of life. Rates of spanking for American Indian and White children were similar at all three time points (age 1, age 3, and age 5).

Phenotypic and Functional Characterization of Müller Glia Isolated from Induced Pluripotent Stem Cell-Derived Retinal Organoids: Improvement of Retinal Ganglion Cell Function upon Transplantation.

Glaucoma is one of the leading causes of blindness, and there is an ongoing need for new therapies. Recent studies indicate that cell transplantation using Müller glia may be beneficial, but there is a need for novel sources of cells to provide therapeutic benefit. In this study, we have isolated Müller glia from retinal organoids formed by human induced pluripotent stem cells (hiPSCs) in vitro and have shown their ability to partially restore visual function in rats depleted of retinal ganglion cells by NMDA.

Comparative proteomic analysis of normal and gliotic PVR retina and contribution of Müller glia to this profile.

Müller glia are responsible for the neural retina regeneration observed in fish and amphibians throughout life. Despite the presence of these cells in the adult human retina, there is no evidence of regeneration occurring in humans following disease or injury. It may be possible that factors present in the degenerated retina could prevent human Müller glia from proliferating and neurally differentiating within the diseased retina.

The impact of stepfamily relationship quality on emerging adult non-medical use of prescription drugs.

Background: Emerging adults aged 18 to 25 are most at-risk for non-medical use of prescription drugs (NMUPD). While the literature dedicated to emerging-adult NMUPD has explored risk and protective factors at an individual level, much less is known regarding how interpersonal and familial factors relate to NMUPD. Because interpersonal bonds can have a significant impact on behavior, familial factors may be important predictors of NMUPD among emerging adults.

Protective Effects of Memantine on Hydroquinone-Treated Human Retinal Pigment Epithelium Cells and Human Retinal Müller Cells.

Purpose: Memantine (MEM) acts on the glutamatergic system by blocking N-methyl-d-aspartate (NMDA) glutamate receptors. The role that MEM plays in protecting retinal cells is unknown. Hydroquinone (HQ) is one of the cytotoxic components in cigarette smoke.

Posterior Vitreous Detachment and the Posterior Hyaloid Membrane.

Purpose: Despite posterior vitreous detachment being a common ocular event affecting most individuals in an aging population, there is little consensus regarding its precise anatomic definition. We investigated the morphologic appearance and molecular composition of the posterior hyaloid membrane to determine whether the structure clinically observed enveloping the posterior vitreous surface after posterior vitreous detachment is a true basement membrane and to postulate its origin. Understanding the relationship between the vitreous (in both its attached and detached state) and the internal limiting membrane of the retina is essential to understanding the cause of rhegmatogenous retinal detachment and vitreoretinal interface disorders, as well as potential future prophylactic and treatment strategies.

Comparison of proteomic profiles in the zebrafish retina during experimental degeneration and regeneration.

Zebrafish spontaneously regenerate the retina after injury. Although the gene expression profile has been extensively studied in this species during regeneration, this does not reflect protein function. To further understand the regenerative process in the zebrafish, we compared the proteomic profile of the retina during injury and upon regeneration.

Characteristics and vitreoretinal management of retinal detachment in eyes with Boston keratoprosthesis.

Purpose: To review the incidence and features of vitreoretinal complications of a permanent Boston keratoprosthesis and to report the use and outcomes of 23-gauge vitrectomy to manage vitreoretinal pathology.

Design: Retrospective non-comparative, interventional case series.

Subject, Participants: 27 eyes of 27 patients managed with a Boston keratoprosthesis at Moorfields Eye Hospital over a 3-year period.

Allogeneic Transplantation of Müller-Derived Retinal Ganglion Cells Improves Retinal Function in a Feline Model of Ganglion Cell Depletion.

Human Müller glia with stem cell characteristics (hMGSCs) have been shown to improve retinal function upon transplantation into rat models of retinal ganglion cell (RGC) depletion. However, their translational potential may depend upon successful engraftment and improvement of retinal function in experimental models with anatomical and functional features resembling those of the human eye. We investigated the effect of allogeneic transplantation of feline Müller glia with the ability to differentiate into cells expressing RGC markers, following ablation of RGCs by N-methyl-d-aspartate (NMDA).

Brimonidine Can Prevent In Vitro Hydroquinone Damage on Retinal Pigment Epithelium Cells and Retinal Müller Cells.

Purpose: Brimonidine is a selective alpha-2 adrenergic agonist used to reduce intraocular pressure and it has been shown to have some neuroprotective effects. Hydroquinone (HQ) is a toxicant present in cigarette smoke, and other sources. In this study, we investigated the cyto-protective effects in vitro of Brimonidine on human retinal pigment epithelium cells (ARPE-19) and human retinal Müller cells (MIO-M1) that had been treated with HQ.

Müller glia as an important source of cytokines and inflammatory factors present in the gliotic retina during proliferative vitreoretinopathy.

Retinal gliosis is characterized by biochemical and physiological changes that often lead to Müller glia proliferation and hypertrophy and is a feature of many neuro-degenerative and inflammatory diseases such as proliferative vitreoretinopathy (PVR). Although Müller glia are known to release inflammatory factors and cytokines, it is not clear whether cytokine production by these cells mirrors the pattern of factors present in the gliotic retina. Lysates from normal cadaveric retina and gliotic retinal specimens from patients undergoing retinectomy for treatment of PVR, the Müller cell line MIO-M1 and four human Müller glial cell preparations isolated from normal retina were examined for their expression of cytokines and inflammatory factors using semi-quantitative dot blot antibody arrays and quantitative arrays.

Amyloid β Peptide Induces Apoptosis Through P2X7 Cell Death Receptor in Retinal Cells: Modulation by Marine Omega-3 Fatty Acid DHA and EPA.

Retinal Müller glial cells have already been implicated in age-related macular degeneration (AMD). AMD is characterized by accumulation of toxic amyloid-β peptide (Aβ); the question we raise is as follows: is P2X7 receptor, known to play an important role in several degenerative diseases, involved in Aβ toxicity on Müller cells? Retinal Müller glial cells were incubated with Aβ for 48 h. Cell viability was assessed using the alamarBlue assay and cytotoxicity using the lactate dehydrogenase (LDH) release assay.

Downregulation of the Canonical WNT Signaling Pathway by TGFβ1 Inhibits Photoreceptor Differentiation of Adult Human Müller Glia with Stem Cell Characteristics.

Müller glia are responsible for the retina regeneration observed in zebrafish. Although the human retina harbors Müller glia with stem cell characteristics, there is no evidence that they regenerate the retina after disease or injury. Transforming growth factor-β (TGFβ) and Wnt signaling regulate retinal neurogenesis and inflammation, but their roles in the neural differentiation of human Müller stem cells (hMSC) are not known.

Effects of light on retinal pigment epithelial cells, neurosensory retinal cells and Müller cells treated with Brilliant Blue G.

Background: The aim of this study is to evaluate the safety profile of Brilliant Blue G (BBG) with and without exposure to light (L) on three different retinal cell lines.

Method: ARPE-19, R28 and MIO-M1 cells were treated with BBG: 0.125 mg/mL (0.

Short Communication: Contribution of Voltage-Gated Sodium Channels to the Rabbit Cone Electroretinograms.

Purpose: Although the rabbit eye is of a similar size to the human eye, our limited understanding of the differences in retinal physiology to other species hinders its use in retinal research. The role of voltage-gated sodium channels (Nav) in the propagation of excitatory potentials along bipolar cells remains unclear, as conflicting data have been reported in the rabbit. The present study assesses the relative contributions of Nav to the scotopic and photopic flash ERGs as well as the wavelength-dependence of Nav blockade on the rabbit flicker ERG.