title: Newer targets for modulation of intraocular pressure: focus on adenosine receptor signaling pathways.
abstract: BACKGROUND
  The homeostatic role of adenosine in regulating intraocular pressure (IOP) is now widely recognized, and hence, the drugs targeting adenosine receptors have become the focus of investigation. In this review, we summarize the adenosine receptor signaling pathways, which could be potential therapeutic targets for the management of glaucoma.
  
  
  METHODS
  This review presents a brief summary of the current hypotheses explaining the increased resistance in the trabecular meshwork outflow pathways and the role of adenosine in regulating the outflow pathway resistance. The intraocular distribution of adenosine receptor subtypes and their structure is described. The adenosine receptor signaling pathways, including activation of adenylyl cyclase, phospholipase-inositol triphosphate-diacylglycerol and phosphatidylinositol-3-kinase and their link to MAPK pathways leading to changes in gene transcription are discussed in detail. The literature search for this review was done using PubMed using several key words such as adenosine, receptors, signaling pathways, trabecular meshwork, ciliary body, IOP, G proteins, GPCR, adenylyl cyclase, phospholipase C, ERK1/2 and MAPKs.
  
  
  CONCLUSIONS
  Besides adenosine receptor agonists and antagonists, drugs targeting intracellular signaling molecules, such as Ras proteins, small GTPase (Rho), Epac-specific cAMP analogs and Rap and Raf-targeted therapies may be useful strategies in regulating IOP.
authors.affiliation: Universiti Teknologi MARA, Faculty of Medicine, UiTM Sungai Buloh Campus , 47000, Sungai Buloh, Selangor , Malaysia +60 361267232 ; renu@salam.uitm.edu.my.
authors.forename: Renu
authors.initials: R
authors.lastname: Agarwal
authors.forename: Puneet
authors.initials: P
authors.lastname: Agarwal
mesh_terms: D000241:Adenosine / Q000502:physiology*; D001082:Aqueous Humor / Q000502:physiology; D002924:Ciliary Body / Q000378:metabolism; D015195:Drug Design; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D005901:Glaucoma / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000187:drug effects / Q000502:physiology; D007429:Intraocular Pressure / Q000187:drug effects* / Q000502:physiology; D008958:Models, Molecular; D058990:Molecular Targeted Therapy; D011487:Protein Conformation; D011494:Protein Kinases / Q000502:physiology; D058906:Purinergic P1 Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D058915:Purinergic P1 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D018047:Receptors, Purinergic P1 / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D014129:Trabecular Meshwork / Q000187:drug effects / Q000503:physiopathology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D011494:Protein Kinases; D019204:GTP-Binding Proteins; D000241:Adenosine