Photoreceptor activation drives the expression of the immediate-early gene Egr1 in inner retinal neurons

The immediate-early gene early growth response-1 (Egr1) encodes a zinc finger transcription factor with diverse functions depending on tissue and stimulus, including light. In the retina, Egr1 expression has been often reported in pathological contexts, but its physiological regulation and function remain poorly understood. Here, we used immunofluorescence and real time PCR in wild type and four mutant mouse strains with impaired rod and/or cone vision to determine the cellular origin of the signal that activates Egr1 expression in inner retinal neurons after light onset. We show that physiological light robustly induced EGR1 expression in subsets of bipolar, amacrine, and ganglion cells in wild type mice and mice without rod but intact cone function. When cone function was impaired or lacking, induction of EGR1 expression was severely reduced but not absent, indicating that rods also contributed to signalling to downstream neurons. Only when both rod and cone function were absent did light fail to activate EGR1 expression in inner retinal neurons. Notably, Müller glia and horizontal cells lacked light-activated EGR1 expression. Our results suggest that light-induced EGR1 expression in inner retinal neurons is predominantly cone-driven. The widespread yet cell type-specific expression pattern of EGR1 in light indicates that the transcription factor may play a role in adapting inner retinal cells to environmental conditions. Our data provide the basis to further explore the molecular signalling cascades underlying light-induced EGR1 activation in inner retinal neurons and to study the significance of this response for retinal physiology.