Effects of fluorescent protein tdTomato on mouse retina

Exp Eye Res. 2024 Jun:243:109910. doi: 10.1016/j.exer.2024.109910. Epub 2024 Apr 24.


Fluorescent proteins (FPs) have been widely used to investigate cellular and molecular interactions and trace biological events in many applications. Some of the FPs have been demonstrated to cause undesirable cellular damage by light-induced ROS production in vivo or in vitro. However, it remains unknown if one of the most popular FPs, tdTomato, has similar effects in neuronal cells. In this study, we discovered that tdTomato expression led to unexpected retinal dysfunction and ultrastructural defects in the transgenic mouse retina. The retinal dysfunction mainly manifested in the reduced photopic electroretinogram (ERG) responses and decreased contrast sensitivity in visual acuity, caused by mitochondrial damages characterized with cellular redistribution, morphological modifications and molecular profiling alterations. Taken together, our findings for the first time demonstrated the retinal dysfunction and ultrastructural defects in the retinas of tdTomato-transgenic mice, calling for a more careful design and interpretation of experiments involved in FPs.

Keywords: Deleterious effect; Fluorescent protein; GFP; Mitochondrial defects; ROS; Retinal dysfunction; mtDNA; tdTomato.

MeSH terms

  • Animals
  • Electroretinography*
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic*
  • Mitochondria / metabolism
  • Red Fluorescent Protein
  • Retina* / metabolism
  • Visual Acuity / physiology


  • tdTomato