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What goes wrong in bestrophinopathies?
Many of the processes the photoreceptor cells use to detect light are reliant on听healthy听RPE.听Mutations in BEST1 gene affect the RPE and disrupt these processes.听
Mutations in the BEST1 gene affect the way the BEST1 channel works in the RPE cells.听This could cause an excess or reduction in the transport of chloride ions into the cell, affecting fluid transport, phagocytosis of retinal debris听and other听crucial RPE听functions. Disruption of these activities could cause the听RPE听to swell听or听be less able to process retinal听debris.听The build of retinal waste听can听create听a physical barrier between the RPE听and retina,听stopping听the RPE cells from听looking after the听photoreceptor听cells. Deposits of fatty waste (lipofuscin) can also create a toxic environment resulting in cell death of RPE and photoreceptor cell death.听Ultimately, death of听the RPE听breaks down the听blood:retina听barrier, allowing new blood vessels to grow from the choroid to the retina,听a complication of听bestrophinopathies听called听choroidal neovascularisation.听
The RPE and retinal cells we are born with are not capable of regeneration and they cannot be replaced by the body if they die. Loss of these cells therefore leads to permanent vision loss.听Research is now focusing on defining the role(s) of BEST1 in the RPE, finding out how mutations affect that role, and developing treatments that can prevent cell loss and therefore vision loss.听听