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Editors Selection IGR 15-4

Basic Science: Genetic drivers of aqueous and CSF secretion

Comment by Rand Allingham on:

56198 Gene expression-based comparison of the human secretory neuroepithelia of the brain choroid plexus and the ocular ciliary body: potential implications for glaucoma, Janssen SF; Gorgels TG; ten Brink JB et al., Fluids and barriers of the CNS, 2014; 11: 2

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Janssen and co-workers compare gene expression (transcriptomes) of the non-pigmented neuroepithelial lining of the ciliary body (NPE) and choroid plexus (CPE). These cells secrete aqueous humor and cerebrospinal fluid, thus responsible for generating intraocular pressure (IOP) and cerebrospinal fluid pressure (CSFP), respectively. It has been postulated that the pressure difference experienced by the lamina cribrosa may be important in glaucoma pathogenesis. Therefore, it is of interest to examine the gene expression of these two cell types. Substantial similarities and differences in gene expression among the 30,589 uniquely expressed genes were found. Molecular pathways for neurologic function and disease, neurodegenerative disorders like Alzheimer disease, and immunological pathways were implicated. Surprisingly, 1000 genes were more highly expressed in one epithelium versus the other. A large number of genes (31) that code for ion channels involved in AH and CSF production were highly expressed in one or both epithelia. Transcripts for 19 POAG candidate genes were found. TMCO1, associated with IOP level was highly expressed in both epithelia. A gene implicated in normal tension glaucoma, CDKN2B, was more highly expressed in CPE. Another POAG-risk associated gene, SIX6 was expressed more highly in NPE. Genes involved in congenital glaucoma (CYP1B1) and early-onset forms of glaucoma,(MYOC and PAX6) were expressed more highly in NPE.

This is an excellent paper that helps clarify the role of these cells in processes relevant to glaucoma and other related disorders. The presence and expression level of specific genes helps clarify which may be important in carrying out key functions in specific cell types. Actively transcribed genes can help determine potential therapeutic targets, for example, the presence of transcripts for alpha-2 adrenoreceptors. The authors note that some alpha-2 adrenergic antagonists reduce IOP while increasing CSF pressure making these agents an attractive therapeutic target. Finally, analyzing specific cells obtained from intact human tissues can provide better understanding and context for what is observed in cell cultures or animal models.

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