Abstract
Primary Congenital Glaucoma (PCG) is an autosomal recessive disease caused by an abnormal development of the anterior chamber angle. Although, PCG has been linked to several genetic loci, the role that the genes at these loci or their encoded proteins play in the pathophysiology of PCG and development of the anterior chamber is not known. To identify proteins that may be altered in PCG and that may help in understanding the underlying pathophysiology of the disease, we took a global proteomics approach. Tryptic digests of the complex mixtures of proteins in aqueous humor were analyzed using Liquid Chromatography/Mass Spectrometry (LC-MS/MS). Proteins were identified by searching the data against the human subset of the UniProt database. The proteomes of aqueous humor in PCG (n = 7) and patients undergoing cataract surgery as control (n = 4) were compared based on the scan counts of comparable proteins. Using stringent filtering criteria, Apolipoprotein A-IV (APOA-IV), Albumin and Antithrombin 3 (ANT3) were detected at significantly higher levels in PCG AH compared to control, whereas Transthyretin (TTR), Prostaglandin-H2 D-isomerase (PTGDS), Opticin (OPT) and Interphotoreceptor Retinoid Binding Protein (IRBP) were detected at significantly lower levels. Many of these proteins play a role in retinoic acid (RA) binding/transport and have been implicated in the pathogenesis of neurodegenerative diseases such as Alzheimer’s (AD). It is possible that similar to AD, the pathologic changes in PCG during development could be influenced by the availability of RA in the anterior chamber.
►Several proteins were differentially expressed in Primary Congenital Glaucoma (PCG) aqueous humor when compared to controls. ►Many differentially expressed proteins appear to be involved in retinoic acid transport. ►The panel of these proteins is similar to that described in the CSF in Alzheimer’s disease.