Modulating the Transport Characteristics of Bruch's Membrane With Steroidal Glycosides and its Relevance to Age-Related Macular Degeneration (AMD).

Abstract

Beneficial expectations of supplement therapies to increase the transport of nutrients, vitamins, and antioxidants across Bruch's membrane in AMD, by mass action alone, remain inconclusive. Therefore, the potential for targeting the transport pathways themselves to improve bidirectional exchange using amphipathic steroidal glycosides (ginsenosides) has been investigated. Bruch's choroid preparations were mounted in modified Ussing chambers and basal levels of hydraulic conductivity (23 donors, age range, 12-89 years) and diffusional transport of FITC-albumin (21 donors, age range, 12-92 years) quantified. Then, following a 24-hour incubation with ginsenoside preparations, the transport parameters were re-evaluated and the resulting data analyzed with respect to aging and modulation by ginsenosides. Basal hydraulic conductivity of Bruch's showed an age-related exponential decline with a half-life of 19 years. Incubation with ginsenosides improved hydraulic conductivity with levels equivalent to donors 19 years younger. Across the age range examined, hydraulic conductivities were increased to 2.05-fold ± 0.38 (P < 0.001) of basal values. Diffusional transport of albumin across Bruch's also showed an age-related exponential decline with a half-life of 18 years. The decay curves were elevated on incubation with ginsenosides and diffusional rates were equivalent to donors 15 years younger. Diffusional rates were elevated 2.01-fold ± 0.49 over basal values (P < 0.001). Transport characteristics of human Bruch's can be improved by ginsenosides, facilitating the bidirectional exchange of nutrients and waste products across the membrane. With improved transport pathways, the need for supplement therapies becomes redundant. Slowed aging of Bruch's is expected to delay the onset and/or progression of AMD.