Saponin-Mediated Rejuvenation of Bruch’s Membrane: A New Strategy for Intervention in Dry Age-Related Macular Degeneration (AMD)

Abstract

At present, there is no treatment modality for the vast majority of patients with dry AMD. The pathophysiology of AMD is complex but current evidence suggests that abnormal ageing of Bruch's membrane imparts a metabolic insult to the retinal pigment epithelium (RPE) and photoreceptor cells that leads eventually to the inflammatory-mediated death of these cells. Underlying mechanisms contributing to the pathology of Bruch's membrane include the accumulation of 'debris' and malfunction of the matrix metalloproteinase (MMP) system resulting in diminished metabolic support of the retina and inefficient removal of toxic pro-inflammatory mediators. Saponins are amphipathic molecules that have a hydrophobic tri-terpenoid lipid region and hydrophilic glycosidic chains that allow for the dispersion of these deposits in Bruch's and re-activation of the MMP system leading to a 2-fold improvement in the transport properties of the membrane. Such an intervention is expected to improve the bi-directional exchange of nutrients and waste products, thereby slowing the progression of dry AMD. This will be the first drug-based interventionist possibility to address dry AMD.