Aims-This study investigated the presence ofthe cytokine tumour necrosis factor a (TNFa) and the vascular adhesion glyco-

This study investigated the presence of mRNA coding for interferon gamma

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. Based on the present results, we suggest that Müller glia derived from retinal organoids formed by hiPSC may provide an attractive source of cells for human retinal therapies, to prevent and treat vision loss caused by retinal degenerative conditions. Stem Cells Translational Medicine 2019;8:775&784

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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. Although they can become reactive under pathological conditions, leading to their production of inflammatory and neurotoxic factors, their main metabolic functions confer neuroprotection to the retina, resulting in the promotion of neural cell repair and survival. In addition to their protective metabolic features, Müller glia release several neurotrophic factors and antioxidants into the retinal microenvironment, which are taken up by retinal neurons for their survival. This review summarizes the Müller glial neuroprotective mechanisms and describes advances made on the clinical application of these factors for the treatment of retinal degenerative diseases. It also discusses prospects for the use of these cells as a vehicle to deliver neuroprotective factors into the retina. ARTICLE HISTORY

Recent advances in retinal stem cell research have raised the possibility that these cells have the potential to be used to repair or regenerate diseased retina. Various cell sources for replacement of retinal neurons have been identified, including embryonic stem cells, the adult ciliary epithelium, adult Müller stem cells and induced pluripotent stem cells (iPS). However, the true stem cell nature of the ciliary epithelium and its possible application in cell therapies has now been questioned, leaving other cell sources to be carefully examined as potential candidates for such therapies. The need for identification of the ontogenetic state of grafted stem cells in order to achieve their successful integration into the murine retina has been recognized. However, it is not known whether the same requirements may apply to achieve transplant cell integration into the adult human eye. In addition, the existence of natural barriers for stem cell transplantation, including microglial accumulation and abnormal extracellular matrix deposition have been demonstrated, suggesting that several obstacles need to be overcome before such therapies may be implemented. This review addresses recent scientific developments in the field and discusses various strategies that may be potentially used to design cell based therapies to treat human retinal disease.

HQ-induced toxicity is mediated through mitochondrial damaging, oxidative stress-related and necrosis-related pathways; Brimonidine significantly prevented the mitochondrial damaging and oxidative stress-related effects but had little effect on blocking the necrosis component of HQ-toxicity. Brimonidine protective effects differ between the different retinal cell types and high concentrations of Brimonidine (10×) have minimal damaging effects on human retinal cells.

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