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. Author manuscript; available in PMC: 2021 Jan 29.
Published in final edited form as: Adv Exp Med Biol. 2019;1185:445–449. doi: 10.1007/978-3-030-27378-1_73

Table 73.1.

Signaling mechanisms involved in PEDF-mediated protection in the retina

Experimental conditions Insult Target cell Time and dose of PEDF treatment Signaling pathway response References
In vivo Pde6 mutation Inherited RP mouse rd1 model photoreceptors 16 h of intravitreal injection of 6 pmol per eye of PEDF Decreased intracellular Ca2+, prevented calpains’ activation, suppressed nuclear translocation of AIF, and attenuated Bax activity Comitato et al. (2018)
Zaprinast (PDE6 inhibitor) Mouse 661W 2 h of 10 nM of PEDF Decreased intracellular Ca2+ and photoreceptor cell death
In vitro Serum starvation Rat R28 30 min of 50–250 ng/ml of PEDF Increased cell survival through STAT3 activation Eichler et al. (2017)
In vitro Light damage Mouse 661W 1–2 h light exposure of 10 nM PEDF Prevented cell death with induction of PI3k/Akt activity Rapp et al. (2014)
In vitro Serum starvation Rat R28 48 h of 100–2500 ng/mL of PEDF Prevented nuclear translocation of AIF and photoreceptor apoptosis by induction of Bcl-2 expression in vivo and in vitro Murakami et al. (2008)
In vivo Retinal degeneration animal model Royal College Surgeon (RCS) rat photoreceptors 2 weeks of subretinal injection of SIV-hPEDF in P21 RCS rats
In vitro Serum starvation Rat R28 6 h of 100 nM PEDF Induced Bcl-2 gene expression through the interaction with PEDF-R Subramanian et al. (2013)
In vitro Oxidative Stress [H2O2] Human ARPE-19 2 h of 50 ng/mLof PEDF preconditioning prior to H2O2 or concentrations higher than 25 ng/uL Suppressed cytotoxicity by induction of ERK1/2 phosphorylation Tsao et al. (2006)
In vitro Oxidative Stress [H2O2] Human ARPE-19 2 h of 50 ng/mL of PEDF preconditioning prior to H2O2 insult Prevented RPE barrier dysfunction, inhibited p38, and HSP27 phosphorylation Ho et al. (2006)
In vitro Oxidative Stress [H2O2] Primary human RPE 1 h of 250 ng/mL of PEDF prior to H2O2 acute injury Reduced cytotoxicity and mitochondrial dysfunction with activation of PI3K/Akt pathway He et al. (2014)
In vitro TNFα/H2O2 Human ARPE-19 4 h of 50 mg/mL of PEDF Synergistic effect with DHA in reducing apoptosis by inducing the expression of Bcl-2 family of proteins; synthesis and release of NPD1 Mukherjee et al. (2007a, b)