Neurotrophic Effects of PEDF & Peptides in the Retina

Article: Scientists unravel the function of a sight-saving growth factor
Source: National Institutes of Health, via NEI
Published: June 16, 2021

PEDF protein and derived peptides

Researchers at the National Eye Institute are studying how a growth factor called pigment epithelium-derived factor (PEDF) protects neurons from cellular stresses such as oxidative stress, inflammation, neovascularization, and cell death. To study the mechanisms behind PEDF's beneficial properties, the team used a cell culture model where immature retinal cells are isolated from the eyes of newborn rats and grown in vitro with minimal nutrients, alongside other types of cells in the retina. They discovered that PEDF has functionally distinct domains, which previous research showed can work independently of the full-length protein. One domain called the 34-mer (formed by 34 amino acid building blocks) halts blood vessel growth. Two other domains called the 44-mer and the 17-mer (a shorter version of the 44-mer) provide anti-apoptotic signals to retinal neurons. The researchers found that like full-length PEDF, both the 44-mer and the 17-mer could preserve photoreceptors from cell death, even in the absence of proteins and cells in the usual retinal environment. Additionally, their research showed that PEDF plays a role in photoreceptor development, triggering the movement of light-sensing opsin into the budding outer segment of photoreceptors where light detection takes place. Another finding showed that the 44-mer and the 17-mer could stimulate amacrine cells, another type of cell in the retina that relays visual information, to grow neurites, projections that facilitate neuronal communication; furthermore, these two fragments were at least as effective, or better, at stimulating these connections as the full-length protein. Finally, the researchers discovered PEDF's function in processing omega-3 fatty acids such as DHA, which is important for eye health both during infant development and for eye health over time. The authors conclude, "Our findings support the neurotrophic PEDF peptides as neuronal guardians for the retina, highlighting their potential as promoters of retinal differentiation, and inhibitors of retina cell death and its blinding consequences."

My rating of this study: ⭐⭐⭐

Michelis G, German OL, Villasmil R, et al. "Pigment Epithelium-derived Factor (PEDF) and Derived Peptides Promote Survival and Differentiation of Photoreceptors and Induce Neurite-outgrowth in Amacrine Neurons." Journal of Neurochemistry. 16 June 2021. https://doi.org/10.1111/jnc.15454