Astrocytes Regulate the Development and Maturation of Retinal Ganglion Cells Derived from Human Pluripotent Stem Cells

SummaryRetinal ganglion cells (RGCs) form the connection between the eye and the brain, with this connectivity disrupted in numerous blinding disorders. Previous studies have demonstrated the ability to derive RGCs from hPSCs; however these cells exhibited some characteristics that indicated a limited state of maturation. Among the many factors known to influence RGC development in the retina, astrocytes are known to play a significant role in their functional maturation. Thus, efforts of the current study examined the functional maturation of hPSC-derived RGCs, including the ability of astrocytes to modulate this developmental timeline. Morphological and functional properties of RGCs were found to increase over time, with astrocytes significantly accelerating the functional maturation of hPSC-derived RGCs. The results of this study are the first of its kind to extensively study the functional and morphological maturation of RGCs in vitro, including the effects of astrocytes upon the maturation of hPSC-derived RGCs.

Download Full-text

The survival of neonatal rat retinal ganglion cells in vitro is enhanced in the presence of appropriate parts of the brain

Experimental Brain Research ◽

10.1007/bf00238614 ◽

1982 ◽

Vol 48 (3) ◽

Cited By ~ 73

Author(s):

C.A. McCaffery ◽

M.R. Bennett ◽

B. Dreher

Keyword(s):

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Neonatal Rat ◽

Retinal Ganglion ◽

The Brain

Download Full-text

A Safe GDNF and GDNF/BDNF Controlled Delivery System Improves Migration in Human Retinal Pigment Epithelial Cells and Survival in Retinal Ganglion Cells: Potential Usefulness in Degenerative Retinal Pathologies

Pharmaceuticals ◽

10.3390/ph14010050 ◽

2021 ◽

Vol 14 (1) ◽

pp. 50

Author(s):

Alicia Arranz-Romera ◽

Maria Hernandez ◽

Patricia Checa-Casalengua ◽

Alfredo Garcia-Layana ◽

Irene T. Molina-Martinez ◽

...

Keyword(s):

Cell Viability ◽

Retinal Ganglion Cells ◽

Neurotrophic Factor ◽

Retinal Pigment Epithelial ◽

Ganglion Cells ◽

Retinal Pigment ◽

Terminal Deoxynucleotidyl Transferase ◽

Retinal Ganglion ◽

Pigment Epithelial

We assessed the sustained delivery effect of poly (lactic-co-glycolic) acid (PLGA)/vitamin E (VitE) microspheres (MSs) loaded with glial cell-derived neurotrophic factor (GDNF) alone (GDNF-MSs) or combined with brain-derived neurotrophic factor (BDNF; GDNF/BDNF-MSs) on migration of the human adult retinal pigment epithelial cell-line-19 (ARPE-19) cells, primate choroidal endothelial (RF/6A) cells, and the survival of isolated mouse retinal ganglion cells (RGCs). The morphology of the MSs, particle size, and encapsulation efficiencies of the active substances were evaluated. In vitro release, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability, terminal deoxynucleotidyl transferase (TdT) deoxyuridine dUTP nick-end labelling (TUNEL) apoptosis, functional wound healing migration (ARPE-19; migration), and (RF/6A; angiogenesis) assays were conducted. The safety of MS intravitreal injection was assessed using hematoxylin and eosin, neuronal nuclei (NeuN) immunolabeling, and TUNEL assays, and RGC in vitro survival was analyzed. MSs delivered GDNF and co-delivered GDNF/BDNF in a sustained manner over 77 days. The BDNF/GDNF combination increased RPE cell migration, whereas no effect was observed on RF/6A. MSs did not alter cell viability, apoptosis was absent in vitro, and RGCs survived in vitro for seven weeks. In mice, retinal toxicity and apoptosis was absent in histologic sections. This delivery strategy could be useful as a potential co-therapy in retinal degenerations and glaucoma, in line with future personalized long-term intravitreal treatment as different amounts (doses) of microparticles can be administered according to patients’ needs.

Download Full-text

Use of Purified Retinal Ganglion Cells for an In Vitro Model to Study Glaucoma

Ophthalmology Research™ - Mechanisms of the Glaucomas ◽

10.1007/978-1-59745-373-8_32 ◽

2008 ◽

pp. 601-607 ◽

Cited By ~ 1

Author(s):

Yasumasa Otori

Keyword(s):

Retinal Ganglion Cells ◽

In Vitro Model ◽

Ganglion Cells ◽

Retinal Ganglion ◽

Vitro Model

Download Full-text

Photoreceptive retinal ganglion cells control the information rate of the optic nerve

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1810701115 ◽

2018 ◽

Vol 115 (50) ◽

pp. E11817-E11826 ◽

Cited By ~ 20

Author(s):

Nina Milosavljevic ◽

Riccardo Storchi ◽

Cyril G. Eleftheriou ◽

Andrea Colins ◽

Rasmus S. Petersen ◽

...

Keyword(s):

Optic Nerve ◽

Retinal Ganglion Cells ◽

Information Flow ◽

Information Transfer ◽

Ganglion Cells ◽

Retinal Ganglion ◽

Ambient Light ◽

Visual Responses ◽

Light Irradiance ◽

The Brain

Information transfer in the brain relies upon energetically expensive spiking activity of neurons. Rates of information flow should therefore be carefully optimized, but mechanisms to control this parameter are poorly understood. We address this deficit in the visual system, where ambient light (irradiance) is predictive of the amount of information reaching the eye and ask whether a neural measure of irradiance can therefore be used to proactively control information flow along the optic nerve. We first show that firing rates for the retina’s output neurons [retinal ganglion cells (RGCs)] scale with irradiance and are positively correlated with rates of information and the gain of visual responses. Irradiance modulates firing in the absence of any other visual signal confirming that this is a genuine response to changing ambient light. Irradiance-driven changes in firing are observed across the population of RGCs (including in both ON and OFF units) but are disrupted in mice lacking melanopsin [the photopigment of irradiance-coding intrinsically photosensitive RGCs (ipRGCs)] and can be induced under steady light exposure by chemogenetic activation of ipRGCs. Artificially elevating firing by chemogenetic excitation of ipRGCs is sufficient to increase information flow by increasing the gain of visual responses, indicating that enhanced firing is a cause of increased information transfer at higher irradiance. Our results establish a retinal circuitry driving changes in RGC firing as an active response to alterations in ambient light to adjust the amount of visual information transmitted to the brain.

Download Full-text