Sex-Dependent Responses in the Retina Proteome to Ocular Hypertension in a Mouse Model of Glaucoma

Mass spectrometry-based retina proteomics is an emerging method applied to a better understanding of glaucomatous neurodegeneration. This study reports the identification of retinal proteins and processes associated with elevated intraocular pressure using the magnetic microbead model of glaucoma in mice with consideration of sex as a biological variable. The harvested retinas were analyzed by shotgun proteomics via nanoflow liquid chromatography-electrospray ionization tandem mass spectrometry and label-free quantifications. Ingenuity Pathway Analysis^® was used for biological interpretation of the resulting dataset. Sex had a statistically significant influence on elevated intraocular pressure-induced changes of retinal protein expressions, and principal component analysis of all identified, verified, and quantified proteins indicated a clear separation of the ocular hypertensive versus normotensive clusters in males, while this separation was far less pronounced in females. Metabolic functions were among the most predominant biological features affected by the increased intraocular pressure. While our results overlapped with many previous findings regarding disease pathology, they have also revealed previously unreported proteins, as well as molecular and physiological functions potentially implicated in glaucomatous neurodegeneration of the retina in a sex-dependent manner.