The bestrophin family was first identified in humans by linking a mutation in the BEST1 gene with Best vitelliform macular dystrophy (BVMD), a degenerative retinal disease . Mutations in the BEST1 gene have been identified as the primary cause for at least five different degenerative retinal diseases .
Bestrophin-1 is predominantly expressed in the retinal pigment epithelium (RPE), a layer of cells in the eye that is vital for vision . When stimulated by calcium ions, Bestrophin-1 opens up to allow chloride ions to flow into and out of the cell . This chloride ion flow is essential for maintaining the health of the human eye and is believed to be involved in the eye’s response to light .
Bestrophin-1 has been studied extensively to understand its structure and function. The protein’s structure has been resolved in complex with an Fab antibody fragment, chloride, and calcium . This structural information has provided insights into how Bestrophin-1 functions as a calcium-activated chloride channel.
Mutations in the BEST1 gene lead to various retinal degenerative diseases, which can result in progressive vision loss and even blindness . Over two hundred disease-causing mutations have been identified in the BEST1 gene . These mutations impair Bestrophin-1’s ability to mediate calcium-dependent chloride currents in the RPE, which is crucial for normal visual function .
Recent research has focused on understanding the molecular mechanisms of BEST1 mutations and their impact on Bestrophin-1 function . Using patient-specific induced pluripotent stem cell (iPSC)-based disease models, researchers have been able to analyze the effects of specific BEST1 mutations and explore potential therapeutic approaches . One promising approach involves viral gene supplementation to rescue the function of mutant Bestrophin-1 in patient-derived RPE cells .