Alterations in molecular pathways in the retina of early experimental XXXX eyes.

@entity726 @entity8027 @entity735 @entity179 @entity5180
@entity726 is a multifactorial, @entity179 . The molecular mechanisms that underlie the pathophysiological changes in @entity735 , especially at the early stage of the disease, are poorly understood. Here, we report the findings from a quantitative proteomic analysis of retinas from experimental @entity726 (EG) eyes. An early stage of EG was modeled on unilateral eyes of five nonhuman primates (NHP) by laser treatment-induced elevation of intraocular pressure (IOP). Retinal proteins were extracted from individual EG eyes and their contralateral control eyes of the same animals, respectively, and analyzed by quantitative mass spectrometry (MS). As a result, a total, 475 retinal proteins were confidently identified and quantified. Results of bioinformatic analysis of proteins that showed an increase in the EG eyes suggested changes in apoptosis, DNA damage, immune response, cytoskeleton rearrangement and cell adhesion processes. Interestingly, hemoglobin subunit alpha ( @entity8027 ) and Ras related C3 botulinum toxin substrate 1 ( @entity5180 ) were among the increased proteins. Results of molecular modeling of @entity8027 - and @entity5180 -associated signaling network implicated the involvement of Mitogen-Activated Protein Kinase (MAPK) pathway in the EG, through which @entity5180 may exert a regulatory role on @entity8027 . This is the first observation of this potentially novel signaling network in the NHP retina and in EG. Results of Western blot analyses for @entity5180 , @entity8027 and a selected MAPK pathway protein indicated synergistic changes in all three proteins in the EG eyes. Further, results of hierarchical cluster analysis of proteomes of control eyes revealed a clear age-proteome relationship, and such relationship appeared disrupted in the EG eyes. In conclusion, our results suggested an increased presence of a potentially novel signaling network at the early stage of @entity726 , and age might be one of the determinant factors in retinal proteomic characteristics under normal conditions.
