Effects of fluorescent protein tdTomato on mouse retina

Topics:

Ocular and CNS Toxicity Models

Retinal Ganglion Cell Pathology

Toxicity

Publication

Experimental Eye Research (Apr 24, 2024) Effects of fluorescent protein tdTomato on mouse retina

Zhang CJ, Mou H, Yuan J, Wang YH, Sun SN, Wang W, Xu ZH, Yu SJ, Jin K, Jin ZB

DOI: 10.1016/j.exer.2024.109910 >>

The authors showed that expression of tdTomato in transgenic mice causes retinal dysfunction: photopic ERG responses are reduced, and contrast sensitivity is impaired, as demonstarted with Striatech’s OptoDrum. The cause appears to be mitochondrial disfunction associated with ultrastructural abnormalities. These findings indicate that tdTomato can adversely affect retinal neuronal function.

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.