Ali Hussain

By Yunhee Lee, Eun Jung Ahn and Ali Hussain

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.

Part of the book: Recent Advances and New Perspectives in Managing Macular Degeneration

By Yunhee Lee and Ali A. Hussain

The earliest functional marker in age-related macular degeneration (AMD) is the delayed recovery of rod photoreceptor sensitivity following a bright flash. Underlying mechanism is thought to be reduced levels of retinoids in the retinal pigment epithelium (RPE) compromising the rate of transfer of 11-cis retinal to the photoreceptor for rhodopsin regeneration. Normally, retinoids are lost due to photo-oxidation in the photoreceptor cell and inefficient processing of outer segment discs by the RPE but this loss is compensated for by delivery of plasma retinol across Bruch’s membrane. Ageing of Bruch’s membrane is associated with a 10-fold decrease in capacity for transport that is further exaggerated in AMD. We had previously shown that saponins can remove deposits from Bruch’s membrane resulting in improved transport. As a proof-of-principle we have undertaken a pilot study with six AMD patients on oral saponin supplementation for 2 months (200 mg saponins/day) to assess the possibility of improving the transport across Bruch’s membrane. Saponin supplementation improved the rate of recovery in rod sensitivity following a bright flash in all AMD subjects (p < 0.005. paired t-test), indicative of improved delivery of retinol across Bruch’s membrane. The saponin intervention provides a new approach to slow, halt, or reverse the progression of AMD.

Part of the book: Macular Diseases - An Update [Working title]