Control of early cell death by BDNF in the chick retina

Development ◽  
1997 ◽  
Vol 124 (17) ◽  
pp. 3313-3320 ◽  
Author(s):  
J.M. Frade ◽  
P. Bovolenta ◽  
J.R. Martinez-Morales ◽  
A. Arribas ◽  
J.A. Barbas ◽  
...  

The developing chick retina undergoes at least two discrete periods of programmed cell death. The earlier period coincides with the main onset of neuron birth and migration (embryonic day 5–7), whereas the latter one corresponds to the well-documented process of retinal ganglion cell death following tectal innervation (embryonic day 10–14; Rager, G. H. (1980) Adv. Anat. Embryol. Cell Biol. 63, 1–92). In the early period, apoptosis is induced by nerve growth factor (NGF) acting via its p75 receptor (Frade, J. M., Rodriguez-Tebar, A. and Barde, Y.-A. (1996) Nature 383, 166–168). Here, we show that the application of brain-derived neurotrophic factor (BDNF) to chick embryos in ovo prevented retinal cell death in the early period, whereas exogenously applied NGF and neurotrophin-3 had no such effect. The addition of BDNF to embryos resulted in about 70% increase in the number of retinal ganglion cells in both E6 and E9 retinas relative to controls. BDNF is first expressed in both the pigment epithelium and neural retina of embryonic day 4 embryos, and at the same stage of development, its TrkB receptor is expressed in the neural retina. Our data indicate that early cell death is an important process in the neurogenesis of retinal ganglion cells and is regulated by locally produced BDNF.


2018 ◽  
Vol 1 (1) ◽  
pp. 23-29 ◽  
Author(s):  
Takashi Kanamoto ◽  
Yasushi Kitaoka ◽  
Hiroaki Sakaue ◽  
Yusuke Murakami ◽  
Yasuhiro Ikeda ◽  
...  

Purpose: The purpose of this study is to investigate the role of free D-serine in the death of retinal cells caused by ocular hypertension.Methods: Adult Wistar rats were used as an experimental model of ocular hypertension. Immunohistochemistry was used to identify the retinal sites and expression patterns of D-serine and serine racemase in the rat retina. The concentrations of free D-serine and L-serine in the retina were measured by two-dimensional high-performance liquid chromatography. Retinal cell death was investigated by Immunohistochemistry.Results: D-serine was expressed on the retinal ganglion cell layer in the retinas of rats with ocular hypertension. A serine racemase was specifically expressed in the retinal ganglion cells. The ratio of free D-/L-serine in the retinas with ocular hypertension was higher than that in the retinas with normal tension. Annexing-V-positive cells were observed in the retinal ganglion cell layer in the retinas of the rats with ocular hypertension, and these cells were also co-localized with D-serine expression.Conclusions: We suspect that the up-regulation of serine racemase expression induced by ocular hypertensionleads to an increase in free D-serine converted from free L-serine in retinal ganglion cells and that retinal cell death is associated with D-serine expression.



1992 ◽  
Vol 9 (3-4) ◽  
pp. 389-398 ◽  
Author(s):  
Luiz R. G. Britto ◽  
Dȃnia E. Hamassaki-Britto

AbstractA small number of enkephalin-like immunoreactive cells were observed in the ganglion cell layer of the pigeon retina. Many of these neurons were identified as ganglion cells, since they were retrogradely labeled after injections of fluorescent latex microspheres in the contralateral optic tectum. These ganglion cells were mainly distributed in the inferior retina, and their soma sizes ranged from 12–26 μm in the largest axis. The enkephalin-containing ganglion cells appear to represent only a very small percentage of the ganglion cells projecting to the optic tectum (less than 0.1%). Two to 7 weeks after removal of the neural retina, there was an almost complete elimination of an enkephalin-like immunoreactive plexus in layer 3 of the contralateral, rostrodorsal optic tectum. These data provide evidence for the existence of a population of enkephalinergic retinal ganglion cells with projections to the optic tectum.





Development ◽  
1999 ◽  
Vol 126 (24) ◽  
pp. 5713-5724 ◽  
Author(s):  
K.L. McCabe ◽  
E.C. Gunther ◽  
T.A. Reh

Neurons in both vertebrate and invertebrate eyes are organized in regular arrays. Although much is known about the mechanisms involved in the formation of the regular arrays of neurons found in invertebrate eyes, much less is known about the mechanisms of formation of neuronal mosaics in the vertebrate eye. The purpose of these studies was to determine the cellular mechanisms that pattern the first neurons in vertebrate retina, the retinal ganglion cells. We have found that the ganglion cells in the chick retina develop as a patterned array that spreads from the central to peripheral retina as a wave front of differentiation. The onset of ganglion cell differentiation keeps pace with overall retinal growth; however, there is no clear cell cycle synchronization at the front of differentiation of the first ganglion cells. The differentiation of ganglion cells is not dependent on signals from previously formed ganglion cells, since isolation of the peripheral retina by as much as 400 μm from the front of ganglion cell differentiation does not prevent new ganglion cells from developing. Consistent with previous studies, blocking FGF receptor activation with a specific inhibitor to the FGFRs retards the movement of the front of ganglion cell differentiation, while application of exogenous FGF1 causes the precocious development of ganglion cells in peripheral retina. Our observations, taken together with those of previous studies, support a role for FGFs and FGF receptor activation in the initial development of retinal ganglion cells from the undifferentiated neuroepithelium peripheral to the expanding wave front of differentiation.



2019 ◽  
Vol 181 ◽  
pp. 285-293 ◽  
Author(s):  
Xiaoyun Ma ◽  
Yun Zhang ◽  
Dan Zhu ◽  
Zufeng Chen ◽  
Manshan Xu ◽  
...  


2009 ◽  
Vol 102 (5) ◽  
pp. 2982-2993 ◽  
Author(s):  
David Tsai ◽  
John W. Morley ◽  
Gregg J. Suaning ◽  
Nigel H. Lovell

In the last decade several groups have been developing vision prostheses to restore visual perception to the profoundly blind. Despite some promising results from human trials, further understanding of the neural mechanisms involved is crucial for improving the efficacy of these devices. One of the techniques involves placing stimulating electrodes in the subretinal space between the photoreceptor layer and the pigment epithelium to evoke neural responses in the degenerative retina. This study used cell-attached and whole cell current-clamp recordings to investigate the responses of rabbit retinal ganglion cells (RGCs) following subretinal stimulation with 25-μm-diameter electrodes. We found that direct RGC responses with short latency (≤2 ms using 0.1-ms pulses) could be reliably elicited. The thresholds for these responses were reported for on, off, and on–off RGCs over pulse widths 0.1–5.0 ms. During repetitive stimulation these direct activation responses were more readily elicited than responses arising from stimulation of the retinal network. The temporal spiking characteristics of RGCs were characterized as a function of stimulus configurations. We found that the response profiles could be generalized into four classes with distinctive properties. Our results suggest that for subretinal vision prostheses short pulses are preferable for efficacy and safety considerations, and that direct activation of RGCs will be necessary for reliable activation during high-frequency stimulation.



2016 ◽  
Vol 234 ◽  
pp. 68-80 ◽  
Author(s):  
Carlos G. Martínez-Moreno ◽  
José Ávila-Mendoza ◽  
Yilun Wu ◽  
Elvira del Carmen Arellanes-Licea ◽  
Marcela Louie ◽  
...  


1990 ◽  
Vol 4 (3) ◽  
pp. 217-223 ◽  
Author(s):  
Ngoh Ngoh Tung ◽  
Ian G. Morgan ◽  
David Ehrlich

AbstractThe present study examines the differential effects of three excitotoxins, kainic acid (KA), N-methyl-D-aspartate (NMDA), and α-amino-2,3-amino-2,3-dihydro-5- methyl-3-oxo-4- isoxazolepropanoic acid (AMPA) on neurons within the genglion cell layer (GCL) of the chick retina. Two-day-old chicks were given a single, 5 μl, intravitreal injection of KA, NMDA, or AMPA at a range of doses. Following treatment with 40 nmol KA, there was a 21% loss of neurons in the GCL. At 200 nmol KA, the loss increased to 46%. Exposure to KA eliminated mainly small neurons of soma area 5–15μm2, and medium-sized ganglion cells of soma area 15–25μm2. Large ganglion cells (>25μ,2) remained unaffected. The vast majority of small cells were probably displaced amarcrine cells. At a does of 3000 nmol NMDA, no further loss of cells was evident. Exposure to 200 nmol AMPA resulted in a 30% loss of large and some medium-sized ganglion cells. In a further series of experiments, exposure to excitotoxin was followed by a retinal scratch, which eliminated retinal ganglion cells within the axotomized region. The results indicate that only a small proportion of displaced amacrine cells are destroyed by NMDA and AMPA, whereas virtually all displaced amarine cells are sensitive to KA. The findings of this study indicate the existence of subclasses of ganglion cells with specificity towards different types of excitatory amino acids (EAA).



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