Neuroprotective Effect of Intraperitoneal Humanin-G in Retinal Degeneration of Royal College of Surgeons Rats

This study aimed to examine whether Humanin-G (HNG), a mitochondrial derived peptide with cytoprotective properties, could improve the retinal function and gene expression in Royal College of Surgeons (RCS) rats with retinal pigment epithelium (RPE) dysfunction and retinal degeneration. Starting at postnatal day 21, RCS rats received twice a week intraperitoneal injection of either Low Dose HNG (0.4 mg/kg), High Dose HNG (4mg/kg), or sham-saline for 1 or 4 weeks. Visual function was tested with electroretinography (ERG) and optokinetic testing (OKT). Then the rats were euthanized for RNA, cDNA and Quantitative Real-time PCR (qRT-PCR) analysis. The results showed that high dose HNG at 4 weeks after first injection (WAFI) was associated with the largest change in gene expression in the RPE and retina of treated animals, altering expression of genes involved in apoptosis, oxidative stress, inflammation and retinal/RPE function. At 4 WAFI, ERG showed no difference between either low or high dose of HNG and sham injection, while the visual acuity in rats treated with high dose HNG showed significant improvement. Our findings suggested that HNG can modulate gene expression and improve vision, thus may be a potential treatment for retinal degeneration diseases.