The BEST1 gene:

The BEST1 gene provides instructions for making the protein bestrophin-1, which plays a critical role in normal vision, specifically at the level of the retina pigment epithelium (RPE)1.

Bestrophin-1 functions as a channel across cell membranes in the retinal pigment epithelium. Charged chloride ions are transported through these channels in response to cellular signals.

Mutations in the BEST1 gene alter the ionic channel functions of the protein and cause ionic imbalance in the RPE1

  • Dysfunction of bestrophin-1 causes accumulated fluid that is present in earlier stages of Best’s disease
  • Impaired ionic flow across the RPE is thought to alter the relationship between the RPE and photoreceptors, reducing the phagocytosis of the photoreceptor outer segments by the RPE that is known to increase lipofuscin accumulation

Lipofuscin deposition is an early hallmark sign of Best disease

  • Lipofuscin, a byproduct of incompletely phagocytosed photoreceptor outer segments, is found in a number of aging and diseased tissues, including the RPE2
  • Lipofuscin will accumulate in the RPE when its ability to break down outer segments of photoreceptors is compromised. While this occurs naturally with age, excess accumulation is considered pathologic and may occur with RPE cell dysfunction or abnormal metabolic load on the RPE2
  • Lipofuscin itself generates reactive oxygen species which likely contributes to the pathogenesis of various retina diseases1