Inflammatory stimulation preserves physiological properties of retinal ganglion cells after optic nerve injury

Stutzki, Henrike; Leibig, Christian; Andreadaki, Anastasia; Fischer, Dietmar; Zeck, Günther

doi:10.3389/fncel.2014.00038

Cited by 32 publications

(25 citation statements)

References 54 publications

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“…To evaluate the functionality of RGCs, spontaneous RGC activity was measured in MEA recordings. We analysed the number of electrodes that recorded spontaneous RGC spiking, which has previously been established as a good marker of physiological integrity of the retinal explants . Seventy‐five minutes of hypoxia severely reduced the spontaneous RGC activity to 33.1% ( P < .01 compared to control) (Figure ).…”

Section: Resultsmentioning

confidence: 99%

“…We analysed the number of electrodes that recorded spontaneous RGC spiking, which has previously been established as a good marker of physiological integrity of the retinal explants. 16,17 Seventy-five minutes of hypoxia severely reduced the spontaneous RGC activity to 33.1% (P < .01 compared to control) ( Figure 5). When the retinal explants were kept under hypothermic conditions during and beyond hypoxia, the hypoxia-induced functional loss could be restored.…”

Section: Hypothermia Rescues Spontaneous Rgc Activitymentioning

confidence: 92%

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Hypothermia protects retinal ganglion cells against hypoxia‐induced cell death in a retina organ culture model

Klemm

Hurst

Blak

et al. 2019

Clinical Exper Ophthalmology

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Background Hypoxia contributes to retinal damage in several retinal diseases, including central retinal artery occlusion, with detrimental consequences like painless, monocular loss of vision. Currently, the treatment options are severely limited due to the short therapy window, as the neuronal cells, especially the retinal ganglion cells (RGCs), are irreversibly damaged within the first few hours. Hypothermia might be a possible treatment option or at least might increase the therapy window. Methods To investigate the neuroprotective effect of hypothermia after retinal hypoxia, an easy‐to‐use ex vivo retinal hypoxia organ culture model developed in our laboratory was used that reliably induced retinal damage on a structural, molecular and functional level. The neuroprotective effect of hypothermia after retinal hypoxia was analysed using optical coherence tomography scans, histological stainings, quantitative real‐time polymerase chain reaction, western blotting and microelectrode array recordings. Results Two different hypothermic temperatures (30°C and 20°C) were evaluated, both exhibited strong neuroprotective effects. Most importantly, hypothermia increased RGC survival after retinal hypoxia. Furthermore, hypothermia counteracted the hypoxia‐induced RGC death, reduced macroglia activation, attenuated retinal thinning and protected from loss of spontaneous RGC activity. Conclusions These results indicate that already a mild reduction in temperature protects the RGCs against damage and could function as a promising therapeutic option for hypoxic diseases.

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Section: Resultsmentioning

confidence: 99%

Section: Hypothermia Rescues Spontaneous Rgc Activitymentioning

confidence: 92%

Hypothermia protects retinal ganglion cells against hypoxia‐induced cell death in a retina organ culture model

Klemm

Hurst

Blak

et al. 2019

Clinical Exper Ophthalmology

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“…Extracellular recordings of retinal ganglion cells (RGCs) spiking activity were performed using planar and transparent microelectrode arrays (MEA; Multi Channel Systems, Reutlingen, Germany, http://www.multichannelsystems.com/) as recently reported . Briefly, retinas of dark‐adapted mice were isolated from the eye cup under dim red light illumination, cut in half, and placed ganglion cell side down on an electrode array comprising 252 electrodes (electrode diameter: 10 µm, electrode spacing: 60 µm).…”

Section: Methodsmentioning

confidence: 99%

Daylight Vision Repair by Cell Transplantation

et al. 2014

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Human daylight vision depends on cone photoreceptors and their degeneration results in visual impairment and blindness as observed in several eye diseases including age-related macular degeneration, cone-rod dystrophies, or late stage retinitis pigmentosa, with no cure available. Preclinical cell replacement approaches in mouse retina have been focusing on rod dystrophies, due to the availability of sufficient donor material from the rod-dominated mouse retina, leaving the development of treatment options for cone degenerations not well studied. Thus, an abundant and traceable source for donor cone-like photoreceptors was generated by crossing neural retina leucine zipper-deficient (Nrl 2/2 ) mice with an ubiquitous green fluorescent protein (GFP) reporter line resulting in double transgenic tg(Nrl 2/2 ; aGFP) mice. In Nrl 2/2 retinas, all rods are converted into cone-like photoreceptors that express CD73 allowing their enrichment by CD73-based magnetic activated cell sorting prior transplantation into the subretinal space of adult wild-type, cone-only (Nrl 2/2 ), or cone photoreceptor function loss 1 (Cpfl1) mice. Donor cells correctly integrated into host retinas, acquired mature photoreceptor morphology, expressed cone-specific markers, and survived for up to 6 months, with significantly increased integration rates in the cone-only Nrl 2/2 retina. Individual retinal ganglion cell recordings demonstrated the restoration of photopic responses in cone degeneration mice following transplantation suggesting, for the first time, the feasibility of daylight vision repair by cell replacement in the adult mammalian retina. STEM CELLS 2015;33:79-90

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“…D) Signal trace recorded by a metal‐based TiN electrode of a passive MEA, following the protocol described in ref. . E) Single extracellular voltage trace recorded underneath one retinal ganglion cell using a capacitive CMOS MEA electrode (open square symbols) and a TiN electrode (filled square).…”

Section: Biotechnological Constrains Of “Electrical Imaging”mentioning

confidence: 99%

Electrical Imaging: Investigating Cellular Function at High Resolution

et al. 2017

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recently membrane currents from skeletal myotubes, [7] from glia or from glia-derived cancerogenic glioma cells [8] or from pancreatic beta cells [9] have been reported. In brain or muscle tissues different cell types interact. As a consequence the generated electrical signals comprise a rich frequency content ranging from few Hertz to several kilohertz. [10] Electrical signaling on sub-millisecond time scale occurs during so-called action potentials, when the transmembrane potential changes rapidly due to the opening and closing of voltagegated sodium channels.In this review we will discuss biotechnological aspects relevant for the "electrical imaging" technique and highlight applications in neuroscience. Related recent reviews discussed some of the technological backgrounds of microelectrode arrays [11] and some of their applications. [6] To estimate the requirements needed to image the electrical activity in neurons and networks, we summarize important scales and numbers. A typical neuron comprises a cell body, which integrates the presynaptic signals using an elaborate dendritic network (dendritic tree) and sends an action potential (stereotyped transmembrane voltage signal) activity to synaptically connected neurons using a thin axonal cable-like fiber. Mammalian cell bodies are typically about 10-20 µm in diameter, while the cable-like dendritic and axonal structures have diameters ranging between a few tens of nanometers up to several micrometers. [12] The entire dendritic tree of one neuron or of a synaptically connected neuronal network may cover an area ranging between few tens of micrometers up to tens of square millimeter. [12] Within the retinal ganglion cell layer or hippocampal cell layers the neuronal density may be as high as 5000-10 000 cells mm −2 (mouse retinal ganglion cells, [13] granule cells), [14] to name just two prominent neural tissues studied so far using electrical imaging. These numbers highlight the spatial range and resolution to be achieved for imaging the electrically activity generated and propagating therein at (sub) cellular resolution.Optical imaging-the most common imaging modality in life sciences-achieves high-resolution digital imaging by magnifying and recording the light signal using a complementary metal-oxide semiconductor (CMOS) camera chip. Relevant parameters for optical imaging comprise (i) a large field of view, (ii) a high signal-to-noise ratio (SNR), and (iii) high spatial and (iv) high temporal resolution. The ratio between the sensitivity of the CMOS sensors (i.e., minimal number of detected photons) and the corresponding pixel noise sets the sensitivity limit.Electrical imaging-potentially a complementary or alternative technique of optical imaging-deals with the same constrains. Here, instead of a light-detecting CMOS camera chip, the changing Electrical imaging of extracellular potentials reveals the activity of electrogenic cells and of networks thereof over several orders of magnitude, both in space and time. On a spatial scale, electrical activity pro...

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Inflammatory stimulation preserves physiological properties of retinal ganglion cells after optic nerve injury

Cited by 32 publications

References 54 publications

Hypothermia protects retinal ganglion cells against hypoxia‐induced cell death in a retina organ culture model

Hypothermia protects retinal ganglion cells against hypoxia‐induced cell death in a retina organ culture model

Daylight Vision Repair by Cell Transplantation

Electrical Imaging: Investigating Cellular Function at High Resolution

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