Eye drop delivery of pigment epithelium-derived factor-34 promotes retinal ganglion cell neuroprotection and axon regeneration

摘要: Axotomised retinal ganglion cells (RGCs) die rapidly by apoptosis and fail to regenerate because of the limited availability neurotrophic factors a lack axogenic stimuli. However, we have recently showed that pigment epithelium-derived factor (PEDF) promotes RGC survival axon regeneration after optic nerve crush injury. PEDF has multiple fragments native peptide are neuroprotective, anti-angiogenic anti-inflammatory. Here investigated neuroprotective properties fragment PEDF, PEDF-34, in neurons vitro when delivered intravitreal injection eye drops vivo. We found PEDF-34 was 43% more 52% neuritogenic than PEDF-44 vitro. Moreover, vivo, delivery 1.88nM 71% at 21days compared intact controls, whilst daily containing promoted 87% survival. After topical drop delivery, detected vitreous body within 30min attained physiologically relevant concentrations retina 4h peaking 1.4±0.05nM 14days. In drop- intravitreal-treated animals, 55% axons regenerated 250μm beyond lesion. conclude application is superior weekly injections promoting through both direct effects on indirect other cells.