Fig. 6: Blockade of PEDF by zinc may contribute to neurodegeneration in glaucoma.
a In the healthy retina, PEDF is a component of normal trophic support of RGCs that is secreted by Müller cells and stimulates phospholipase A2 activity of PEDF-R, resulting in increased production of DHA and upregulation of other neurotrophic factors such as BDNF. b In glaucoma, oxidative stress causes the release of mobile zinc from metallothioneins (MTs) into the extracellular space, which triggers apoptotic signaling in RGCs. Under these conditions, PEDF is intensely secreted by retinal cells but becomes inactive because zinc binding reduces its negative surface charge and promotes oligomerization, which impairs the neuroprotective and regenerative activity of the protein. Along with suppression of other Zn2+-sensitive neurotrophic factors (BDNF, NGF, etc.) that support RGCs growth and survival, this mechanism contributes to neurodegeneration in glaucoma.
