Modulation of proinflammatory activity by the engineered cationic antimicrobial peptide WLBU-2.

Background: Host-derived (LL-37) and synthetic (WLBU-2) cationic antimicrobial peptides (CAPs) are known for their membrane-active bactericidal properties. LL-37 is an important mediator for immunomodulation, while the mechanism of action of WLBU-2 remains unclear.

Objective: To determine if WLBU-2 induces an early proinflammatory response that facilitates bacterial clearance in cystic fibrosis (CF).

Increased expression of glutathione peroxidase 4 strongly protects retina from oxidative damage.

Oxidative damage contributes to cone cell death in retinitis pigmentosa and death of rods, cones, and retinal pigmented epithelial (RPE) cells in age-related macular degeneration. In this study, we explored the strategy of overexpressing components of the endogenous antioxidant defense system to combat oxidative damage in RPE cells and retina. In transfected cultured RPE cells with increased expression of superoxide dismutase1 (SOD1) or SOD2, there was increased constitutive and stress-induced oxidative damage measured by the level of carbonyl adducts on proteins.

Oxidative stress modulates complement factor H expression in retinal pigmented epithelial cells by acetylation of FOXO3.

Age-related macular degeneration (AMD), the leading cause of severe vision loss in the elderly, is a complex disease that results from genetic modifications that increase susceptibility to environmental exposures. Smoking, a major source of oxidative stress, increases the incidence and severity of AMD, and antioxidants slow progression, suggesting that oxidative stress plays a major role. Polymorphisms in the complement factor H (CFH) gene that reduce activity of CFH increase the risk of AMD.

Trans-scleral delivery of polyamine analogs for ocular neovascularization.

Periocular injections of the polyamine analog CGC-11144 three times a week causes regression of choroidal neovascularization. This regimen was selected to maximize chances of success for proof of concept, but is not ideal for clinical application. In this study we explored other regimens for periocular delivery of CGC-11144, and 2 other polyamine analogs, CGC-11047 and CGC-11093.