The Effect of PKCα on the Light Response of Rod Bipolar Cells in the Mouse Retina

Invest Ophthalmol Vis Sci. 2015 Jul;56(8):4961-74. doi: 10.1167/iovs.15-16622.

Abstract

Purpose: Protein kinase C α (PKCα) is abundantly expressed in rod bipolar cells (RBCs) in the retina, yet the physiological function of PKCα in these cells is not well understood. To elucidate the role of PKCα in visual processing in the eye, we examined the effect of genetic deletion of PKCα on the ERG and on RBC light responses in the mouse.

Methods: Immunofluorescent labeling was performed on wild-type (WT), TRPM1 knockout, and PKCα knockout (PKC-KO) retina. Scotopic and photopic ERGs were recorded from WT and PKC-KO mice. Light responses of RBCs were measured using whole-cell recordings in retinal slices from WT and PKC-KO mice.

Results: Protein kinase C alpha expression in RBCs is correlated with the activity state of the cell. Rod bipolar cells dendrites are a major site of PKCα phosphorylation. Electroretinogram recordings indicated that loss of PKCα affects the scotopic b-wave, including a larger peak amplitude, longer implicit time, and broader width of the b-wave. There were no differences in the ERG a- or c-wave between PKCα KO and WT mice, indicating no measurable effect of PKCα in photoreceptors or the RPE. The photopic ERG was unaffected consistent with the lack of detectable PKCα in cone bipolar cells. Whole-cell recordings from RBCs in PKC-KO retinal slices revealed that, compared with WT, RBC light responses in the PKC-KO retina are delayed and of longer duration.

Conclusions: Protein kinase C alpha plays an important modulatory role in RBCs, regulating both the peak amplitude and temporal properties of the RBC light response in the rod visual pathway.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • DNA / genetics*
  • Disease Models, Animal
  • Electroretinography
  • Gene Expression Regulation*
  • Genetic Therapy / methods
  • Immunohistochemistry
  • Mice
  • Mice, Knockout
  • Patch-Clamp Techniques
  • Protein Kinase C-alpha / biosynthesis
  • Protein Kinase C-alpha / genetics*
  • Retinal Bipolar Cells / enzymology*
  • Retinal Bipolar Cells / pathology
  • Retinal Diseases / enzymology
  • Retinal Diseases / genetics*
  • Retinal Diseases / physiopathology
  • Retinal Rod Photoreceptor Cells / enzymology*
  • Retinal Rod Photoreceptor Cells / pathology
  • Visual Pathways / enzymology*
  • Visual Pathways / physiopathology

Substances

  • DNA
  • Protein Kinase C-alpha