Bestrophin 1 and retinal disease

Area of Science:

• Ophthalmology and genetics
• Molecular and cellular biology

Background:

• Mutations in the BEST1 gene cause five distinct retinal degenerative diseases, termed bestrophinopathies.
• Bestrophin 1 (Best1) is a protein crucial for retinal function, acting as an anion channel and calcium signaling regulator.
• Best1 is primarily expressed in the retinal pigment epithelium, with additional roles in the brain.

Purpose of the Study:

• To review current knowledge of Bestrophin 1 (Best1) protein function and its association with retinal diseases.
• To discuss the potential for developing new therapies for bestrophinopathies.

Main Methods:

• Analysis of the crystal structure of Best1 to understand its ion channel and calcium regulation mechanisms.
• Utilizing animal models to investigate the physiological roles of Best1.
• Employing stem cell technology to create patient-derived "disease in a dish" models.

Main Results:

• The crystal structure of Best1 provides insights into its ion channel function and calcium regulation.
• Animal models have elucidated key physiological roles of Best1.
• Patient-derived stem cell models facilitate disease research.

Conclusions:

• Bestrophin 1 (Best1) is a vital protein implicated in several retinal diseases.
• Understanding Best1's structure and function is advancing research towards potential treatments for bestrophinopathies.
• Near-term clinical trials are being considered for these currently untreatable retinal conditions.