A New Therapeutic Option for Reversing the Deficits in Dark Adaptation Associated with Age-Related Macular Degeneration (AMD)

Abstract

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.