scholarly journals Pigment Epithelium-Derived Factor (PEDF) Receptors Are Involved in Survival of Retinal Neurons

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.

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

1991 ◽  
Vol 113 (2) ◽  
pp. 405-416 ◽  
Author(s):  
I de Curtis ◽  
V Quaranta ◽  
R N Tamura ◽  
L F Reichardt

The integrin alpha 6 beta 1 is a prominent laminin receptor used by many cell types. In the present work, we isolate clones and determine the primary sequence of the chick integrin alpha 6 subunit. We show that alpha 6 beta 1 is a prominent integrin expressed by cells in the developing chick retina. Between embryonic days 6 and 12, both retinal ganglion cells and other retinal neurons lose selected integrin functions, including the ability to attach and extend neurites on laminin. In retinal ganglion cells, we show that this is correlated with a dramatic decrease in alpha 6 mRNA and protein, suggesting that changes in gene expression account for the developmental regulation of the interactions of these neurons with laminin. In other retinal neurons the expression of alpha 6 mRNA and protein remains high while function is lost, suggesting that the function of the alpha 6 beta 1 heterodimer in these cells is regulated by posttranslational mechanisms.


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

2003 ◽  
Vol 112 (1-2) ◽  
pp. 126-134 ◽  
Author(s):  
Kenji Kashiwagi ◽  
Yoko Iizuka ◽  
Seiichi Mochizuki ◽  
Yuichi Tsumamoto ◽  
Hiromu K Mishima ◽  
...  

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 113 (21) ◽  
pp. 6047-6052 ◽  
Author(s):  
Diego Carlos Fernandez ◽  
Yi-Ting Chang ◽  
Samer Hattar ◽  
Shih-Kuo Chen

The suprachiasmatic nucleus (SCN) receives direct retinal input from the intrinsically photosensitive retinal ganglion cells (ipRGCs) for circadian photoentrainment. Interestingly, the SCN is the only brain region that receives equal inputs from the left and right eyes. Despite morphological assessments showing that axonal fibers originating from ipRGCs cover the entire SCN, physiological evidence suggests that only vasoactive intestinal polypeptide (VIP)/gastrin-releasing peptide (GRP) cells located ventrally in the SCN receive retinal input. It is still unclear, therefore, which subpopulation of SCN neurons receives synaptic input from the retina and how the SCN receives equal inputs from both eyes. Here, using single ipRGC axonal tracing and a confocal microscopic analysis in mice, we show that ipRGCs have elaborate innervation patterns throughout the entire SCN. Unlike conventional retinal ganglion cells (RGCs) that innervate visual targets either ipsilaterally or contralaterally, a single ipRGC can bilaterally innervate the SCN. ipRGCs form synaptic contacts with major peptidergic cells of the SCN, including VIP, GRP, and arginine vasopressin (AVP) neurons, with each ipRGC innervating specific subdomains of the SCN. Furthermore, a single SCN-projecting ipRGC can send collateral inputs to many other brain regions. However, the size and complexity of the axonal arborizations in non-SCN regions are less elaborate than those in the SCN. Our results provide a better understanding of how retinal neurons connect to the central circadian pacemaker to synchronize endogenous circadian clocks with the solar day.


2016 ◽  
Vol 215 (2) ◽  
pp. 147-149 ◽  
Author(s):  
Jeremy N. Kay

Newborn neuron radial migration is a key force shaping the nervous system. In this issue, Icha et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201604095) use zebrafish retinal ganglion cells as a model to investigate the cell biological basis of radial migration and the consequences for retinal histogenesis when migration is impaired.


Sign in / Sign up

Export Citation Format

Share Document