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.

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.

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.

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.

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).

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.

Optimized feline vitrectomy technique for therapeutic stem cell delivery to the inner retina.

Objective: To describe an optimized surgical technique for feline vitrectomy which reduces bleeding and aids posterior gel clearance in order to facilitate stem cell delivery to the inner retina using cellular scaffolds.

Procedures: Three-port pars plana vitrectomies were performed in six-specific pathogen-free domestic cats using an optimized surgical technique to improve access and minimize severe intraoperative bleeding.

Results: The surgical procedure was successfully completed in all six animals.

Transplantation of photoreceptors derived from human Muller glia restore rod function in the P23H rat.

Müller glia possess stem cell characteristics that have been recognized to be responsible for the regeneration of injured retina in fish and amphibians. Although these cells are present in the adult human eye, they are not known to regenerate human retina in vivo. Human Müller glia with stem cell characteristics (hMSCs) can acquire phenotypic and genotypic characteristics of rod photoreceptors in vitro, suggesting that they may have potential for use in transplantation strategies to treat human photoreceptor degenerations.

Acquisition of RGC phenotype in human Müller glia with stem cell characteristics is accompanied by upregulation of functional nicotinic acetylcholine receptors.

Purpose: Human Müller glia with stem cell characteristics (hMGSCs) can be induced to express genes and proteins of retinal ganglion cells (RGCs) upon in vitro inhibition of Notch-1 activity. However, it is not known whether expression of these markers is accompanied by acquisition of RGC function. This study investigated whether hMGSCs that express RGC markers also display neural functionality, as measured by their intracellular calcium concentration ([Ca(2+)]i) responsiveness following neurotransmitter stimulation in vitro.

Gene expression and protein distribution of ADAMTSL-4 in human iris, choroid and retina.

Background: Mutations in ADAMTSL4 have recently been shown to be the major cause of autosomal recessive isolated ectopia lentis (IEL). However, the function and ocular localisation of the protein is yet to be fully established. We therefore aimed to confirm the expression of this gene and protein in normal ocular tissue.

SP-SR interneurones: a novel class of neurones of the CA2 region of the hippocampus.

The CA2 region of the hippocampus has distinctive properties and inputs and may be linked with the pathology of specific psychiatric and neurological disorders. It is, therefore, important to understand CA2 circuitry and its involvement in the circuitry of the hippocampus. Properties of CA2 basket cells have been reported.

Local circuitry involving parvalbumin-positive basket cells in the CA2 region of the hippocampus.

There is a growing recognition that the CA2 region of the hippocampus has its own distinctive properties, inputs, and pathologies. The dendritic and axonal patterns of some interneurons in this region are also strikingly different from those described previously in CA1 and CA3. The local circuitry in this region, however, had yet to be studied in detail.