Abstract
Retinal ganglion cells (RGCs) are the output neuron of the eye, transmitting visual information from the retina through the optic nerve to the brain. The importance of RGCs for vision is demonstrated in blinding diseases where RGCs are lost, such as in glaucoma or after optic nerve injury. In the present study, we hypothesize that normal RGC function is transcriptionally regulated. To test our hypothesis, we examine large retinal expression microarray datasets from recombinant inbred mouse strains in GeneNetwork and define transcriptional networks of RGCs and their subtypes. Two major and functionally distinct transcriptional networks centering around Thy1 and Tubb3 (Class III beta-tubulin) were identified. Each network is independently regulated and modulated by unique genomic loci. Meta-analysis of publically available data confirms that RGC subtypes are differentially susceptible to death, with alpha-RGCs and intrinsically photosensitive RGCs (ipRGCs) being less sensitive to cell death than other RGC subtypes in a mouse model of glaucoma.
Highlights
The retinal ganglion cell (RGC) is the final output neuron of the retina, projecting through the optic nerve to the brain, where it targets a number of functionally distinct areas: for visual perception, Retinal ganglion cells (RGCs) axons travel to the lateral geniculate nucleus (Chalupa and Günhan, 2004); for the regulation of circadian rhythms, they pass through the suprachiasmatic nucleus (Guido et al, 2010); for eye movements, a group of RGC axons terminates in the superior colliculus (Triplett et al, 2014); and for the pupillary light reflex, RCG axons terminate in the pretectal area (Young and Lund, 1998)
In a meta-analysis of previously published data from a microarray study of a mouse glaucoma model (Howell et al, 2011), we examine the differential effects of this disease state on transcriptional networks in RGC subtypes and confirm intrinsically photosensitive RGCs and alpha-RGCs as more resistant to cell death (Duan et al, 2015)
The present study examines the correlation of gene expression in the retina across the BXD recombinant inbred strain set to define gene networks active in RGCs
Summary
The retinal ganglion cell (RGC) is the final output neuron of the retina, projecting through the optic nerve to the brain, where it targets a number of functionally distinct areas: for visual perception, RGC axons travel to the lateral geniculate nucleus (Chalupa and Günhan, 2004); for the regulation of circadian rhythms, they pass through the suprachiasmatic nucleus (Guido et al, 2010); for eye movements, a group of RGC axons terminates in the superior colliculus (Triplett et al, 2014); and for the pupillary light reflex, RCG axons terminate in the pretectal area (Young and Lund, 1998) Each of these areas receives input from distinct subtypes of RGCs with unique morphological and molecular signatures.
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