Neuroprotective and antiangiogenic actions of PEDF in the eye: molecular targets and therapeutic potential.
Pigment epithelium-derived factor (PEDF) is a 50-kDa protein encoded by a single gene that shows strong conservation across phyla from fish to mammals. It is secreted by the retinal pigment epithelium (RPE) and a select number of other cell types in the eye, as well as by other tissues in the body. PEDF was originally defined by its ability to induce differentiation in retinoblastoma cells. It also promotes a non-proliferative, differentiated state in a number of other cell types. PEDF protects retinal neurons from light damage, oxidative stress and glutamate excitotoxicity. PEDF is also antiangiogenic and can inhibit the growth of blood vessels in the eye induced in a variety of ways. A balance in the levels of PEDF and the proangiogenic factor vascular endothelial growth factor-A is perturbed in a range of retinal neovascular diseases. Some of the pathways by which PEDF exerts its actions on cells have now been defined. Peptide fragments of PEDF carry biological activity and may be valuable therapeutic agents that readily penetrate the eye.
Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT 06520, USA.
Colin J
CJ
Barnstable
Joyce
J
Tombran-Tink
D000595:Amino Acid Sequence; D000818:Animals; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology* / Q000627:therapeutic use; D006801:Humans; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D009414:Nerve Growth Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology* / Q000627:therapeutic use; D018696:Neuroprotective Agents; D015843:Serpins / Q000737:chemistry / Q000235:genetics / Q000502:physiology* / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor