title: Characterizing the "POAGome": A bioinformatics-driven approach to primary open-angle glaucoma.
abstract: Primary open-angle glaucoma (POAG) is a genetically, physiologically, and phenotypically complex neurodegenerative disorder. This study addressed the expanding collection of genes associated with POAG, referred to as the "POAGome." We used bioinformatics tools to perform an extensive, systematic literature search and compiled 542 genes with confirmed associations with POAG and its related phenotypes (normal tension glaucoma, ocular hypertension, juvenile open-angle glaucoma, and primary congenital glaucoma). The genes were classified according to their associated ocular tissues and phenotypes, and functional annotation and pathway analyses were subsequently performed. Our study reveals that no single molecular pathway can encompass the pathophysiology of POAG. The analyses suggested that inflammation and senescence may play pivotal roles in both the development and perpetuation of the retinal ganglion cell degeneration seen in POAG. The TGF-β signaling pathway was repeatedly implicated in our analyses, suggesting that it may be an important contributor to the manifestation of POAG in the anterior and posterior segments of the globe. We propose a molecular model of POAG revolving around TGF-β signaling, which incorporates the roles of inflammation and senescence in this disease. Finally, we highlight emerging molecular therapies that show promise for treating POAG.
authors.affiliation: Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Danford
authors.affiliation: Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: Lana D
authors.initials: LD
authors.lastname: Verkuil
authors.affiliation: Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Choi
authors.affiliation: Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Collins
authors.affiliation: Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: Harini V
authors.initials: HV
authors.lastname: Gudiseva
authors.affiliation: Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Uyhazi
authors.affiliation: Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: Marisa K
authors.initials: MK
authors.lastname: Lau
authors.affiliation: Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: Levi N
authors.initials: LN
authors.lastname: Kanu
authors.affiliation: Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA, Penn Center for Bioinformatics, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Grant
authors.affiliation: Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA. Electronic address: vchavali@mail.med.upenn.edu.
authors.forename: Venkata R M
authors.initials: VRM
authors.lastname: Chavali
authors.affiliation: Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: Joan M
authors.initials: JM
authors.lastname: O'Brien
mesh_terms: D019295:Computational Biology / Q000379:methods*; D005902:Glaucoma, Open-Angle / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D007429:Intraocular Pressure / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000473:pathology
keywords: Gliosis; NFκB; Neurodegeneration; Neuroinflammation; Primary open-angle glaucoma (POAG); Senescence; Senescence-associated secretory phenotype (SASP); TGF-β