scholarly journals Pigment epithelium-derived factor protects retinal ganglion cells

2007 ◽  
Vol 8 (1) ◽  
Author(s):  
Iok-Hou Pang ◽  
Hong Zeng ◽  
Debra L Fleenor ◽  
Abbot F Clark

2020 ◽  
Vol 22 (1) ◽  
pp. 369
Author(s):  
Susanne Bürger ◽  
Jie Meng ◽  
Annette Zwanzig ◽  
Mike Beck ◽  
Maik Pankonin ◽  
...  

The demise of retinal ganglion cells (RGCs) is characteristic of diseases of the retina such as glaucoma and diabetic or ischemic retinopathies. Pigment epithelium-derived factor (PEDF) is a multifunctional secreted protein that mediates neuroprotection and inhibition of angiogenesis in the retina. We have studied expression and regulation of two of several receptors for PEDF, patatin-like phospholipase 2 gene product/PEDF-R and laminin receptor (LR), in serum-starved RGC under normoxia and hypoxia and investigated their involvement in the survival of retinal neuronal cells. We show that PEDF-R and LR are co-expressed in RGC and R28 retinal precursor cells. Expression of both receptors was enhanced in the presence of complex secretions from retinal glial (Müller) cells and upregulated by VEGF and under hypoxic conditions. PEDF-R- and LR-knocked-down cells demonstrated a markedly attenuated expression of anti-apoptotic Bcl-2 family members (Bcl-2, Bcl-xL) and neuroprotective mediators (PEDF, VEGF, BDNF) suggesting that both PEDF-R and LR mediate pro-survival effects of PEDF on RGC. While this study does not provide evidence for a differential survival-promoting influence of either PEDF-R or LR, it nevertheless highlights the importance of both PEDF receptors for the viability of retinal neurons.



2012 ◽  
Vol 37 (7) ◽  
pp. 1524-1533 ◽  
Author(s):  
Jan Darius Unterlauft ◽  
Wolfram Eichler ◽  
Konstantin Kuhne ◽  
Xiu Mei Yang ◽  
Yousef Yafai ◽  
...  




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.



Oncotarget ◽  
2017 ◽  
Vol 8 (52) ◽  
pp. 89793-89801 ◽  
Author(s):  
Chaopeng Li ◽  
Kang Yan ◽  
Wenqi Wang ◽  
Qing Bai ◽  
Changming Dai ◽  
...  


2014 ◽  
Vol 25 (2) ◽  
pp. 234-244 ◽  
Author(s):  
Chizu Nakamoto ◽  
Soh-Leh Kuan ◽  
Amy S. Findlay ◽  
Elaine Durward ◽  
Zhufeng Ouyang ◽  
...  

For correct functioning of the nervous system, the appropriate number and complement of neuronal cell types must be produced during development. However, the molecular mechanisms that regulate the production of individual classes of neurons are poorly understood. In this study, we investigate the function of the thrombospondin-1–like glycoprotein, Nel (neural epidermal growth factor [EGF]-like), in the generation of retinal ganglion cells (RGCs) in chicks. During eye development, Nel is strongly expressed in the presumptive retinal pigment epithelium and RGCs. Nel overexpression in the developing retina by in ovo electroporation increases the number of RGCs, whereas the number of displaced amacrine cells decreases. Conversely, knockdown of Nel expression by transposon-mediated introduction of RNA interference constructs results in decrease in RGC number and increase in the number of displaced amacrine cells. Modifications of Nel expression levels do not appear to affect proliferation of retinal progenitor cells, but they significantly alter the progression rate of RGC differentiation from the central retina to the periphery. Furthermore, Nel protects RGCs from apoptosis during retinal development. These results indicate that Nel positively regulates RGC production by promoting their differentiation and survival during development.



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.



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