Common variants of the apolipoprotein E (APOE) gene have a major impact on the risk of developing Alzheimer's disease (AD). Relative to homozygotes with the common E3 allele, the APOE4 variant (C112R) Show more
Common variants of the apolipoprotein E (APOE) gene have a major impact on the risk of developing Alzheimer's disease (AD). Relative to homozygotes with the common E3 allele, the APOE4 variant (C112R) increases risk by 3.5-fold in E3/E4 heterozygotes and 15-fold in E4 homozygotes. Since the E3 and E4 alleles differ only by a single nucleotide, gene editing of E4 to E3 is a potential strategy to reduce AD risk in E4 homozygotes. Because the APOE pool in the brain is separate from systemic APOE, editing to treat AD would ideally be directed to the brain. Following Show less
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 tha Show more
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. Show less