Muller glial cells span the entire thickness of the tissue, and ensheath all retinal neurons, in vertebrate retinae of all species. This morphological relationship is reflected by a multitude of functional interactions between neurons and Muller cells, including a 'metabolic symbiosis' and the processing of visual information. Muller cells are also responsible for the maintenance of the homeostasis of the retinal extracellular milieu (ions, water, neurotransmitter molecules, and pH). In vascularized retinae, Muller cells may also be involved in the control of angiogenesis, and the regulation of retinal blood flow. Virtually every disease of the retina is associated with a reactive Muller cell gliosis which, on the one hand, supports the survival of retinal neurons but, on the other hand, may accelerate the progress of neuronal degeneration: Muller cells protect neurons via a release of neurotrophic factors, the uptake and degradation of the excitotoxin, glutamate, and the secretion of the antioxidant, glutathione. However, gliotic Muller cells display a dysregulation of various neuron-supportive functions. This contributes to a disturbance of retinal glutamate metabolism and ion homeostasis, and causes the development of retinal edema and neuronal cell death. Moreover, there are diseases evoking a primary Muller cell insufficiency, such as hepatic retinopathy and certain forms of glaucoma. Any impairment of supportive functions of Muller cells, primary or secondary, must cause and/or aggravate a dysfunction and loss of neurons, by increasing the susceptibility of neurons to stressful stimuli in the diseased retina. On the contrary, Muller cells may be used in the future for novel therapeutic strategies to protect neurons against apoptosis (somatic gene therapy), or to differentiate retinal neurons from Muller/stem cells. Meanwhile, a proper understanding of the gliotic responses of Muller cells in the diseased retina, and of their protective vs. detrimental effects, is essential for the development of efficient therapeutic strategies that use and stimulate the neuron-supportive/protective-and prevent the destructive-mechanisms of gliosis.

https://www.springer.com/cda/content/document/productFlyer/productFlyer_978-1-4419-1671-6.pdf?SGWID=0-0-1297-173938007-0

Müller Cells in the Healthy and Diseased Retina

We assessed the feasibility of transplanting a sheet of retinal pigment epithelial (RPE) cells differentiated from induced pluripotent stem cells (iPSCs) in a patient with neovascular age-related macular degeneration. The iPSCs were generated from skin fibroblasts obtained from two patients with advanced neovascular age-related macular degeneration and were differentiated into RPE cells. The RPE cells and the iPSCs from which they were derived were subject to extensive testing. A surgery that included the removal of the neovascular membrane and transplantation of the autologous iPSC-derived RPE cell sheet under the retina was performed in one of the patients. At 1 year after surgery, the transplanted sheet remained intact, best corrected visual acuity had not improved or worsened, and cystoid macular edema was present. (Funded by Highway Program for Realization of Regenerative Medicine and others; University Hospital Medical Information Network Clinical Trials Registry [UMIN-CTR] number, UMIN000011929.)

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1608368

Autologous Induced Stem-Cell–Derived Retinal Cells for Macular Degeneration

https://serval.unil.ch/resource/serval:BIB_3A01220E0FF1.P001/REF.pdf

Central serous chorioretinopathy: Recent findings and new physiopathology hypothesis.

Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is increasingly used for the treatment of a wide variety of retinal diseases, including age-related macular degeneration, diabetic retinopathy and retinal vascular occlusions, and retinopathy of prematurity. Despite encouraging results in halting the disease and improving the vision, intravitreal injection of anti-VEGF agents may be associated with systemic adverse events and devastating ocular complications. In this review, we provide an overview of safety data for intravitreal injection of common anti-VEGF agents.

/pdf/adverse-events-and-complications-associated-with-2xo2vyc8kv.pdf

Adverse events and complications associated with intravitreal injection of anti-VEGF agents: a review of literature

Cellular signaling and factors involved in Müller cell gliosis: neuroprotective and detrimental effects.

Scleral Buckling versus Primary Vitrectomy in Rhegmatogenous Retinal Detachment: A Prospective Randomized Multicenter Clinical Study

Background
Primary pars plana vitrectomy (PPPV) has gained widespread popularity in the treatment of rhegmatogenous retinal detachments (RRD). However, the surgical procedure is still flawed by a significant rate of anatomical and functional failures. The study was conducted to analyse the risk factors for a dissatisfying postoperative outcome.

Primary vitrectomy for rhegmatogenous retinal detachment: an analysis of 512 cases.

A free retinal pigment epithelium-choroid graft in patients with exudative age-related macular degeneration: results up to 7 years.

Heavier than water intraocular tamponades have several theoretical advantages over conventional tamponades, especially in the treatment of complicated retinal detachments and proliferative viteroretinopathy of the lower fundus periphery. However, initial clinical series of various heavy tamponades have reported significant complication rates. Therefore, heavy tamponades have not found widespread acceptance. Three recently developed heavy silicone oil tamponades, Oxane HD, Densiron 68, and HWS 46-3000, are much better tolerated and presently seem to enter routine clinical practice. Literature review of 21 publications on the clinical application of 9 different heavy tamponades (fluorosilicone, C10F18, F6H8, OL62HV, Oxane HD, O62, F6H8-silicone oil mixture, Densiron 68, and HWS 46-3000). The first generation (fluorinated silicone and perfluorocarbon liquids) and second generation (partially fluorinated alkanes) of heavy tamponades were associated with relatively high complication rates, for example, tamponade emulsification, intraocular inflammation, and rise in intraocular pressure. The complication spectrum of the new generation of heavy silicone oils (Oxane HD, Densiron 68, and HWS 46-3000) seems to be comparable to conventional silicone oil tamponades while providing better support for the inferior retina and the posterior pole. The recently developed heavy silicone oil tamponades are safe and effective tools for the use of complicated retinal detachments of the inferior fundus.

/pdf/heavy-tamponade-1-a-review-of-indications-use-and-56hnlw6kn8.pdf

Heinrich Heimann

Papers

Scleral Buckling versus Primary Vitrectomy in Rhegmatogenous Retinal Detachment: A Prospective Randomized Multicenter Clinical Study

Primary vitrectomy for rhegmatogenous retinal detachment: an analysis of 512 cases.

A free retinal pigment epithelium-choroid graft in patients with exudative age-related macular degeneration: results up to 7 years.

Heavy tamponade 1: a review of indications, use, and complications

Polypoidal Choroidal Vasculopathy Masquerading as Neovascular Age-Related Macular Degeneration Refractory to Ranibizumab