Transgenic Expression of Cacna1f Rescues Vision and Retinal Morphology in a Mouse Model of Congenital Stationary Night Blindness 2A (CSNB2A)

Transl Vis Sci Technol. 2020 Oct 14;9(11):19. doi: 10.1167/tvst.9.11.19. eCollection 2020 Oct.


Purpose: Congenital stationary night blindness 2A (CSNB2A) is a genetic retinal disorder characterized by poor visual acuity, nystagmus, strabismus, and other signs of retinal dysfunction resulting from mutations in Cacna1f-the gene coding for the pore-forming subunit of the calcium channel CaV1.4. Mouse models of CSNB2A have shown that mutations causing the disease deleteriously affect photoreceptors and their synapses with second-order neurons. This study was undertaken to evaluate whether transgenic expression of Cacna1f could rescue morphology and visual function in a Cacna1f-KO model of CSNB2A.

Methods: Strategic creation, breeding and use of transgenic mouse lines allowed for Cre-driven retina-specific expression of Cacna1f in a CSNB2A model. Transgene expression and retinal morphology were investigated with immunohistochemistry in retinal wholemounts or cross-sections. Visual function was assessed by optokinetic response (OKR) analysis and electroretinography (ERG).

Results: Mosaic, prenatal expression of Cacna1f in the otherwise Cacna1f-KO retina was sufficient to rescue some visual function. Immunohistochemical analyses demonstrated wild-type-like photoreceptor and synaptic morphology in sections with transgenic expression of Cacna1f.

Conclusions: This report describes a novel system for Cre-inducible expression of Cacna1f in a Cacna1f-KO mouse model of CSNB2A and provides preclinical evidence for the potential use of gene therapy in the treatment of CSNB2A.

Translational relevance: These data have relevance in the treatment of CSNB2A and in understanding how photoreceptor integration might be achieved in retinas in which photoreceptors have been lost, such as retinitis pigmentosa, age-related macular degeneration, and other degenerative conditions.

Keywords: CSNB2A; Cacna1f; Cav1.4; calcium channels; channelopathies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels, L-Type* / genetics
  • Eye Diseases, Hereditary* / genetics
  • Genetic Diseases, X-Linked
  • Mice
  • Mice, Transgenic
  • Myopia
  • Night Blindness* / genetics
  • Retina


  • Cacna1f protein, mouse
  • Calcium Channels, L-Type

Supplementary concepts

  • Night blindness, congenital stationary