Altered voltage-gated ion channel expression around drusen accumulations in induced pluripotent stem cell retinal pigment epithelium model of age-related macular degeneration.
Molly Rowland1, Marzena Kurzawa-Akanbi2, Majlinda Lako2, Gerrit Hilgen1,2
1 Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, UK
2 Biosciences Institute, Faculty of Medical Sciences, Newcastle University, UK
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). The exact cause of AMD is unknown, although it is thought to originate within the RPE and is considered to be 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.
Immunohistochemical analysis was carried out on induced pluripotent stem cell (iPSC) derived RPE cells of low and high-risk AMD (Hallam et al., 2017), using pan markers for voltage-gated sodium and calcium channels, alongside antibodies against complement C5b-9 and C3b, markers for drusen depositions in RPE. Initial data showed altered protein expression of the voltage-gated channels around the drusen accumulations, with aggregated staining relative to drusen accumulations compared to more homogeneous staining in the control low-risk RPE cells. Funds for this study were received from the Academy of Medical Sciences (GH) and the ECR support Northumbria University. Acknowledgement goes to the Northumbria Microscopy Lab for their exceptional service and support during the project.