Bestrophin 1

Bestrophin-1 5T5N Xray Cystallography

Bestrophin 1 (Best1) is a protein that in humans is encoded by the BEST1 gene. This protein is a member of the bestrophin family of anion channels and is primarily expressed in the retinal pigment epithelium (RPE) of the eye. Bestrophin 1 plays a crucial role in the regulation of ion transport and cellular volume in the RPE.

Function

Bestrophin 1 functions as a calcium-activated chloride channel. It is involved in the transport of chloride ions across the cell membrane, which is essential for maintaining the ionic balance and proper functioning of the retinal pigment epithelium. The activity of Bestrophin 1 is regulated by intracellular calcium levels, and it contributes to the generation of the light peak in the electrooculogram (EOG).

Clinical Significance

Mutations in the BEST1 gene are associated with several retinal dystrophies, including Best vitelliform macular dystrophy (BVMD), also known as Best disease, adult-onset vitelliform macular dystrophy (AVMD), and autosomal recessive bestrophinopathy (ARB). These conditions are characterized by the accumulation of lipofuscin in the RPE, leading to progressive vision loss.

Best Vitelliform Macular Dystrophy

Best vitelliform macular dystrophy is an autosomal dominant disorder that typically presents in childhood or adolescence. It is characterized by the presence of a yellowish lesion in the macula, which resembles an egg yolk. Over time, this lesion can break down, leading to atrophy of the RPE and photoreceptor cells, resulting in central vision loss.

Adult-Onset Vitelliform Macular Dystrophy

Adult-onset vitelliform macular dystrophy presents later in life, usually in the fourth or fifth decade. The clinical features are similar to those of Best disease, but the progression is generally slower, and the visual prognosis is better.

Autosomal Recessive Bestrophinopathy

Autosomal recessive bestrophinopathy is a rare condition caused by biallelic mutations in the BEST1 gene. It is characterized by widespread RPE abnormalities, leading to severe visual impairment. Patients may also exhibit angle-closure glaucoma and a shallow anterior chamber.

Structure

Bestrophin 1 is a transmembrane protein with four to six transmembrane domains. The exact topology of the protein is still under investigation, but it is known to form homo-oligomeric complexes that function as chloride channels. The protein's structure is crucial for its function, and mutations that disrupt its conformation can lead to disease.

Research

Ongoing research is focused on understanding the precise mechanisms by which Bestrophin 1 regulates ion transport and how mutations in the BEST1 gene lead to retinal dystrophies. Studies are also exploring potential therapeutic approaches, including gene therapy, to treat conditions associated with BEST1 mutations.

Related Pages

• Best vitelliform macular dystrophy
• Adult-onset vitelliform macular dystrophy
• Autosomal recessive bestrophinopathy
• Retinal pigment epithelium
• Electrooculogram
• Chloride channel