Bestrophin 1 and retinal disease

Adiv A. Johnson, Karina E. Guziewicz, C. Justin Lee, Ravi C. Kalathur, Jose S Pulido, Lihua Y Marmorstein, Alan D Marmorstein

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Mutations in the gene BEST1 are causally associated with as many as five clinically distinct retinal degenerative diseases, which are collectively referred to as the "bestrophinopathies". These five associated diseases are: Best vitelliform macular dystrophy, autosomal recessive bestrophinopathy, adult-onset vitelliform macular dystrophy, autosomal dominant vitreoretinochoroidopathy, and retinitis pigmentosa. The most common of these is Best vitelliform macular dystrophy. Bestrophin 1 (Best1), the protein encoded by the gene BEST1, has been the subject of a great deal of research since it was first identified nearly two decades ago. Today we know that Best1 functions as both a pentameric anion channel and a regulator of intracellular Ca2+ signaling. Best1 is an integral membrane protein which, within the eye, is uniquely expressed in the retinal pigment epithelium where it predominantly localizes to the basolateral plasma membrane. Within the brain, Best1 expression has been documented in both glial cells and astrocytes where it functions in both tonic GABA release and glutamate transport. The crystal structure of Best1 has revealed critical information about how Best1 functions as an ion channel and how Ca2+ regulates that function. Studies using animal models have led to critical insights into the physiological roles of Best1 and advances in stem cell technology have allowed for the development of patient-derived, "disease in a dish" models. In this article we review our knowledge of Best1 and discuss prospects for near-term clinical trials to test therapies for the bestrophinopathies, a currently incurable and untreatable set of diseases.

Original languageEnglish (US)
JournalProgress in Retinal and Eye Research
DOIs
StateAccepted/In press - Nov 11 2016

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Vitelliform Macular Dystrophy
Retinal Diseases
Retinitis Pigmentosa
Retinal Pigment Epithelium
Ion Channels
Neuroglia
Astrocytes
gamma-Aminobutyric Acid
Anions
Glutamic Acid
Membrane Proteins
Stem Cells
Animal Models
Cell Membrane
Clinical Trials
Technology
Mutation
Brain
Research
Genes

Keywords

  • Anion channel
  • Best1
  • Bestrophin
  • Maculopathy
  • Retinal disease
  • Retinal pigment epithelium

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems

Cite this

Johnson, A. A., Guziewicz, K. E., Lee, C. J., Kalathur, R. C., Pulido, J. S., Marmorstein, L. Y., & Marmorstein, A. D. (Accepted/In press). Bestrophin 1 and retinal disease. Progress in Retinal and Eye Research. https://doi.org/10.1016/j.preteyeres.2017.01.006

Bestrophin 1 and retinal disease. / Johnson, Adiv A.; Guziewicz, Karina E.; Lee, C. Justin; Kalathur, Ravi C.; Pulido, Jose S; Marmorstein, Lihua Y; Marmorstein, Alan D.

In: Progress in Retinal and Eye Research, 11.11.2016.

Research output: Contribution to journalArticle

Johnson AA, Guziewicz KE, Lee CJ, Kalathur RC, Pulido JS, Marmorstein LY et al. Bestrophin 1 and retinal disease. Progress in Retinal and Eye Research. 2016 Nov 11. https://doi.org/10.1016/j.preteyeres.2017.01.006
Johnson, Adiv A. ; Guziewicz, Karina E. ; Lee, C. Justin ; Kalathur, Ravi C. ; Pulido, Jose S ; Marmorstein, Lihua Y ; Marmorstein, Alan D. / Bestrophin 1 and retinal disease. In: Progress in Retinal and Eye Research. 2016.
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