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) |