Quantitative proteomic profiling reveals sexual dimorphism in the retina and RPE of C57BL6 mice.

Background: Sex as a biological variable is not a common consideration in molecular mechanistic or preclinical studies of retinal diseases. Understanding the sexual dimorphism of adult RPE and retina under physiological conditions is an important first step in improving our understanding of sex-based physio-pathological mechanisms. Methods: Isobaric tags for relative and absolute quantitation (iTRAQ) were used for quantitative proteomics of male and female mouse retina and RPE (10 mice of each sex for each tissue type). Differentially expressed proteins were subjected to Gene Ontology (GO) analysis and Ingenuity Pathway Analysis (IPA). Results: Differential expression analysis identified 21 differentially expressed proteins in the retina and 58 differentially expressed proteins in the RPE. Ingenuity pathway analysis identified the top canonical pathways differentially activated in the retina to be calcium transport I, nucleotide excision repair, molecular transport and cell death and survival. In the RPE, the top canonical pathways were calcium signaling, dilated cardiomyopathy signaling, actin cytoskeletal signaling and cellular assembly and organization. Conclusions: These results provide insights into sex differences in the retina and RPE proteome of mice and begin to shed clues into the sexual dimorphism seen in retinal diseases. Plain English Summary: According to the Centers for Disease Control and Prevention (CDC) an estimated 93 million adults in the United States are at high risk for serious vision loss. Besides the devastating effect on the individual's quality of life, the economic cost of major vision loss is estimated to increase to $373 billion by 2050. In the United States, the Society for Women's Health Research Women's Eye Health Working Group established that women are at a higher risk of developing loss of vision due to eye diseases such as age-related macular degeneration, thyroid eye disease or glaucoma than men. The innate biological differences between males and females that contribute to disease pathology are unknown. There are several cell types in the back of the eye that are responsible for sight. The retina contains light sensing cells (photoreceptors) that capture photons and transmits them to the brain along neural networks as both chemical and electric signals for visual perception. The retinal pigment epithelium (RPE) is a layer of cells underneath the retina that is critical for the normal functioning of the retina. We investigated quantitative differences in the protein composition in the retina and RPE between male and female mice. Using stringent analyses, we identified potential biological pathways that are different between male and female tissues that could contribute to disease pathology. These findings begin to provide possible mechanisms for the sexual dimorphism of ocular diseases. Highlights: The mouse retina and retinal pigment epithelium (RPE) proteome exhibit significant sex differences at baseline. This dataset will serve as a resource for researchers using mouse models to study ocular physiology and pathology. These findings encourage scientists evaluating protein alterations in mouse models of ocular disease to include a careful comparison of sex (and possibly age) in their experimental design to improve the reproducibility and appropriate interpretation of experiments. [ABSTRACT FROM AUTHOR]