Biomarkers For Neuroinflammation And Satellite Glia Activation In Dry Eye Disease

Abstract

Chronic dry eye (DE) is a burden to society with few effective treatments. Investigations of mechanisms for DE pain are limited by the lack of validated biomarkers and reliable measures of nocifensive behavior in an animal model. To address these issues, we assessed eye wiping behavior and quantified qPCR and protein expression of Activating Transcription Factor 3 (ATF3) and Glial Fibrillary Acidic Protein (GFAP), as markers for neuronal injury and satellite glia activation, respectively, in the trigeminal ganglion (TG) of rat model of tear deficient DE. Eye wipe behavior increased in males and females by 14 days after exorbital gland removal. Protein levels for ATF3 increased by 14d in females, but not in males, while GFAP increased in both sexes. By contrast, mRNA levels for ATF3 and GFAP did not change significantly in either sex. GFAP increases in protein were confirmed by immunohistochemistry as seen by an increase in the number of positively stained cells. The increase in GFAP was associated with an increase eye wipe behavior at 14d. These data suggested that neuron-glial mechanisms that mediate DE pain were different in males and females. We conclude that GFAP, but not ATF3, is a valid biomarker for peripheral sensitization in this rat model of DE.