Acute developmental exposure to doxycycline and sucrose alters retinal function in three commonly used mouse strains

Doxycycline is a widely used tetracycline antibiotic, which has become critical in biomedical research for use with tetracycline-inducible transgenic mouse models. This technology provides an eloquent system for genetic manipulation that has caused significant advancements in our understanding of the function of many genes. However, research into doxycycline has revealed effects on cellular metabolism and correlation with fetal abnormalities in rodent models which can confound research outcomes. As the retina is a highly metabolic tissue, it is imperative to understand how exposure to doxycycline impacts long-term retinal health. To investigate this, we exposed C57Bl/6J mice to doxycycline and sucrose, or only sucrose, for an acute 24h window at key timepoints throughout development. After aging the mice to adulthood, we assessed retinal function via electroretinography (ERG) and retinal structure via histology. We found that acute sucrose exposure at some developmental times caused significant increases in ERG amplitudes and implicit times compared to controls, while acute exposure to doxycycline, particularly during early development, led to significant decreases in ERG amplitudes and implicit times. These findings were supported in two additional mouse strains: the 129S1 SvlmJ inbred strain and the outbred CD1 strain. Our data determines that acute, 24h exposure to sucrose or doxycycline during development causes long-term changes to the retina's ability to respond to light. This emphasizes the importance of proper vehicle controls and the need for caution when using these reagents for vision research studies.