Age-related macular degeneration (AMD) is one of the leading causes of irreversible blindness globally and is associated with increasing prevalence and socioeconomic burden. As a result, additional treatment avenues are under constant investigation. AMD can be characterised into a wet or dry form; wet AMD involves the formation of a pathological neovascular membrane that results in the accumulation of subretinal fluid and/or haemorrhaging and dry AMD is characterised by the presence of protein and lipid deposits, known as drusen, that form beneath the retinal pigment epithelium (RPE). Although wet AMD results in a sudden, severe loss of vision, treatment options are available. Dry AMD is slow progressing and has a high conversion rate into wet AMD before reaching end stage disease. The exact cause of AMD is unknown, although it is thought to originate within the RPE and is multi-factorial with both genetic and environmental factors playing a role. An overlooked potential contributing mechanism to AMD is the dysfunction of ion channels, or channelopathies, with their involvement in AMD pathophysiology being poorly understood.

Induced pluripotent stem cell (iPSC) derived RPE can be used to model AMD, both low (control) and high-risk lines were stained for pan markers of voltage-gated sodium channels (Nav) alongside key RPE cell markers such as CRALBP and ZO1. Early experiments show that Nav is expressed in the cell membrane of iPSC RPE, aligned with Z0-1, a tight junction protein (data obtained from three 24-well inserts). Additionally, drusen were identified using antibodies against complement proteins C3b and C5b-9. Initial data has shown altered Nav localisation relative to drusen formations, with less homogenous and more numerous Nav staining in the high-risk lines (data obtained from six low-risk and six high-risk 12-well inserts). Further experiments will confirm and quantify these fundings, including a physiological characterisation of these ion channels in AMD. Funding for this project has been received from the Academy of Medical Sciences (GH) and the ECR support Northumbria University. Acknowledgement goes to Northumbria Microscopy Lab for their exceptional service and support during the project.