Ghrelin in ocular pathophysiology: From the anterior to the posterior segment

Peptides

Volumn 47, Issue , 2013, Pages 12-19

  Azevedo Pinto, Sara ^a   Pereira Silva, Paulo ^a   Rocha Sousa, Amândio ^a,b  

^a University of Porto   (Portugal)

^b Hospital de SãoJoão   (Portugal)

Author keywords

Ghrelin; GHSR 1a; Glaucoma; Iris muscles; Retinopathy

Indexed keywords

ACETYLCHOLINE; ADENOSINE; ADRENOMEDULLIN; ANGIOPOIETIN 2; ANGIOTENSIN II; CARBACHOL; ENDOTHELIN 1; GALANIN; GHRELIN; GHRELIN RECEPTOR; HYPOXIA INDUCIBLE FACTOR; NATRIURETIC FACTOR; PROSTAGLANDIN; PROSTAGLANDIN SYNTHASE; SOMATOMEDIN C; SOMATOSTATIN; SUBSTANCE P; THROMBOXANE A2; VASCULOTROPIN; VASOACTIVE INTESTINAL POLYPEPTIDE;

ACETYLCHOLINE RELEASE; ADRENERGIC SYSTEM; ANTERIOR EYE SEGMENT; AQUEOUS HUMOR; BLOOD VESSEL OCCLUSION; CILIARY BODY; CILIARY BODY EPITHELIUM; CLINICAL PROTOCOL; DIABETIC RETINOPATHY; ELECTROSTIMULATION; EMBASE; ENZYME LINKED IMMUNOSORBENT ASSAY; IMMUNOFLUORESCENCE; IN SITU HYBRIDIZATION; IN VITRO STUDY; INTRAOCULAR HYPERTENSION; INTRAOCULAR PRESSURE; KINETICS; MEDLINE; MICROVASCULAR ENDOTHELIAL CELL; MUSCLE CONTRACTION; MUSCLE RELAXATION; MUSCLE TONE; NERVE ENDING; NONHUMAN; OPEN ANGLE GLAUCOMA; PATHOPHYSIOLOGY; POSTERIOR EYE SEGMENT; PRIORITY JOURNAL; PROLIFERATIVE RETINOPATHY; PROSTAGLANDIN RELEASE; PSEUDOEXFOLIATION; RABBIT; RADIOIMMUNOASSAY; REAL TIME POLYMERASE CHAIN REACTION; RETINA NEOVASCULARIZATION; RETROLENTAL FIBROPLASIA; REVIEW; RISK FACTOR; SPHINCTER PUPILLAE MUSCLE; STOMACH MUCOSA; SYNAPTOSOME; SYSTEMATIC REVIEW; TRABECULAR MESHWORK; UMBILICAL VEIN ENDOTHELIAL CELL; UVEA; VISUAL SYSTEM FUNCTION;

ANIMALIA; SCOPUS;

GHRELIN; GHSR-1A; GLAUCOMA; IRIS MUSCLES; RETINOPATHY;

ANIMALS; CILIARY BODY; DATABASES, BIBLIOGRAPHIC; GENE EXPRESSION; GHRELIN; GLAUCOMA; HUMANS; HYPERTENSIVE RETINOPATHY; INTRAOCULAR PRESSURE; IRIS; OCULOMOTOR MUSCLES; PROSTAGLANDINS; RECEPTORS, GHRELIN;

EID: 84885147329     PISSN: 01969781     EISSN: 18735169     Source Type: Journal    
DOI: 10.1016/j.peptides.2013.06.011     Document Type: Review

References (119)

1. Ahluwalia A, Li A, Cheng G, Deng X, Tarnawski AS. Reduced ghrelin in endothelial cells plays important mechanistic role in aging-related impairment of angiogenesis. J Physiol Pharmacol 2009;60:29-34.
2. Alexander JP, Samples JR, Van Buskirk EM, Acott TS. Expression of matrix metalloproteinases and inhibitor by human trabecular meshwork. Invest Ophthalmol Vis Sci 1991;32:172-80.
3. Andersson U, Filipsson K, Abbott CR, Woods A, Smith K, Bloom SR, et al. AMP-activated protein kinase plays a role in the control of food intake. J Biol Chem 2004;279:12005-8. (Pubitemid 38445761)
4. Aptel F, Chiquet C, Romanet JP. Intraocular pressure-lowering combination therapies with prostaglandin analogues. Drugs 2012;72:1355-71.
5. Ariyasu H, Takaya K, Tagami T, Ogawa Y, Hosoda K, Akamizu T, et al. Stomach is a major source of circulating Ghrelin, and feeding state determines plasma Ghrelin-like immunoreactivity levels in humans. J Clin Endocrinol Metab 2001;86:4753-8. (Pubitemid 33020516)
6. Arosio M, Ronchi CL, Gebbia C, Cappiello V, Beck-Peccoz P, Peracchi M. Stimulatory effects of ghrelin on circulating somatostatin and pancreatic polypeptide levels. J Clin Endocr Metab 2003;88:701-4. (Pubitemid 36207811)
7. Baatar D, Patel K, Taub DD. The effects of ghrelin on inflammation and the immune system. Mol Cell Endocrinol 2011;340:44-58.
8. Baiguera S,Conconi MT,Guidolin D, Mazzocchi G, Malendowicz LK, Parnigotto PP, et al. Ghrelin inhibits in vitro angiogenic activity of rat brain microvascular endothelial cells. Int J Mol Med 2004;14:849-54.
9. Baldanzi G, Filigheddu N, Cutrupi S, Catapano F, Bonissoni S, Fubini A, et al. Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT. J Cell Biol 2002;159:1029-37. (Pubitemid 36055757)
10. Barr L, Gu FJ. A quantitative model of myosin phosphorylation and the photomechanical response of the isolated sphincter pupillae of the frog iris. BiophysJ 1987;51:895-904.
11. Barreiro ML, Gaytan F, Castellano JM, Suominen JS, Roa J, Gaytan M, et al. Ghrelin inhibits the proliferative activity of immature Leydig cells in vivo and regulates stem cell factor messenger ribonucleic acid expression in rat testis. Endocrinology 2004;145:4825-34. (Pubitemid 39551098)
12. Beaumont NJ, Skinner VO, Tan TM, Ramesh BS, Byrne DJ, MacColl GS, et al. Ghrelin can bind to a species of high density lipoprotein associated with paraoxonase.J Biol Chem 2003;278:8877-80. (Pubitemid 36800362)
13. Bedendi I, Alloatti G, Marcantoni A, Malan D, Catapano F, Ghe C, et al. Cardiac effects of ghrelin and its endogenous derivatives des-octanoyl ghrelin and des-Gln (14)-ghrelin. EurJ Pharmacol 2003;476:87-95. (Pubitemid 37315540)
14. Beding-Barnekow B, Brodin E, Hakanson R. Substance-p, neurokinin-a and neurokinin-b in the ocular response to injury in the rabbit. Br J Pharmacol 1988;95:259-67.
15. Bednarek MA, Feighner SD, Pong SS, McKee KK, Hreniuk DL, Silva MV, et al. Structure-function studies on the new growth hormone-releasing peptide, ghrelin: minimal sequence of ghrelin necessary for activation of growth hormone secretagogue receptor 1a. J Med Chem 2000;43:4370-6. (Pubitemid 32046862)
16. Bradley JM, Vranka J, Colvis CM, Conger DM, Alexander JP, Fisk AS, et al. Effect of matrix metalloproteinases activity on outflow in perfused human organ culture. Invest Ophthalmol Vis Sci 1998;39:2649-58. (Pubitemid 28558223)
17. Broglio F, Gottero C, Benso A, Prodam F, Destefanis S, Gauna C, et al. Effects of ghrelin on the insulin and glycemic responses to glucose, arginine, or free fatty acids load in humans. J Clin Endocr Metab 2003;88:4268-72. (Pubitemid 37153730)
18. Brzozowski T, Konturek PC, Sliwowski Z, Pajdo R, Drozdowicz D, Kwiecien S, et al. Prostaglandin/cyclooxygenase pathway in ghrelin-induced gas-troprotection against ischemia-reperfusion injury. J Pharmacol Exp Ther 2006;319:477-87. (Pubitemid 44455155)
19. Bynke G, Hakanson R, Horig J, Leander S. Bradykinin contracts the pupillary sphincter and evokes ocular inflammation through release of neuronal substance-p. EurJ Pharmacol 1983;91:469-75. (Pubitemid 13037020)
20. Camina JP. Cell biology of the ghrelin receptor. J Neuroendocrinol 2006;18:65-76.
21. Carlini VP, Monzon ME, Varas MM, Cragnolini AB, Schioth HB, Scimonelli TN, et al. Ghrelin increases anxiety-like behavior and memory retention in rats. Biochem Biophys Res Commun 2002;299:739-43. (Pubitemid 36034549)
22. Chan CB, Cheng CH. Identification and functional characterization of two alternatively spliced growth hormone secretagogue receptortranscripts from the pituitary of black seabream Acanthopagrus schlegeli. Mol Cell Endocrinol 2004;214:81-95. (Pubitemid 38210118)
23. Chang L, Zhao J, Yang J, Zhang Z, Du J, Tang C. Therapeutic effects of ghrelin on endotoxic shock in rats. EurJ Pharmacol 2003;473:171-6. (Pubitemid 36929881)
24. Choi KC, Roh SG, Hong YH, Shrestha YB, Hishikawa D, Chen C, et al. The role of ghrelin and growth hormone secretagroogues receptor on rat adipogenesis. Endocrinology 2003;144:754-9. (Pubitemid 36262842)
25. Choppin A, Eglen RM, Hegde SS. Pharmacological characterization of muscarinic receptors in rabbit isolated iris sphincter muscle and urinary bladder smooth muscle. BrJ Pharmacol 1998;124:883-8. (Pubitemid 28312821)
26. Coca-Prados M, Escribano J. New perspectives in aqueous humor secretion and in glaucoma: The ciliary body as a multifunctional neuroendocrine gland. Progr Retinal Eye Res 2007;26:239-62. (Pubitemid 46498798)
27. Conconi MT, Nico B, Guidolin D, Baiguera S, Spinazzi R, Rebuffat P, et al. Ghrelin inhibits FGF-2-mediated angiogenesis in vitro and in vivo. Peptides 2004;25:2179-85. (Pubitemid 39574461)
28. Cullinane ABPS, Leung PS, Ortego J, Coca-Prados M, Harvey BJ. Renin-angiotensin system expression and secretory function in cultured human ciliary body non-pigmented epithelium. Br J Ophthalmol 2002;86:676-83. (Pubitemid 34627960)
29. Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 2001;50:1714-9. (Pubitemid 33641587)
30. Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma MK, Dellinger EP, et al. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. New Engl J Med 2002;346:1623-30. (Pubitemid 34755670)
31. Date Y, Kojima M, Hosoda H, Sawaguchi A, Mondal MS, Suganuma T, et al. Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology 2000;141:4255-61.
32. De Vriese C, Hacquebard M, Gregoire F, Carpentier Y, Delporte C. Ghrelin interacts with human plasma lipoproteins. Endocrinology 2007;148: 2355-62. (Pubitemid 46997038)
33. Ding KH, AbdelLatif AA. Actions of C-type natriuretic peptide and sodium nitroprusside on carbachol-stimulated inositol phosphate formation and contraction in ciliary and iris sphincter smooth muscles. Invest Ophthalmol Vis Sci 1997;38:2629-38.
34. Dixit VD, Schaffer EM, Pyle RS, Collins GD, Sakthivel SK, Palaniappan R, et al. Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells. J Clin Invest 2004;114:57-66. (Pubitemid 39071644)
35. Dornonville de la Cour C, Lindstrom E, Norlen P, Hakanson R. Ghrelin stimulates gastric emptying but is without effect on acid secretion and gastric endocrine cells. Regul Pept 2004;120:23-32. (Pubitemid 38726188)
36. Egido EM, Rodriguez-Gallardo J, Silvestre RA, Marco J. Inhibitory effect of ghrelin on insulin and pancreatic somatostatin secretion. Eur J Endocrinol 2002;146:241-4. (Pubitemid 34162918)
37. Ehinger B. Ocular and orbital vegetative nerves. Acta Physiol Scand Suppl 1966;268:1-35.
38. Ehinger B, Gustafsson-Sporrong B. Adrenergic and cholinergic axons in the mouse iris. Experientia 1966;22:218.
39. El Sayah M, Calixto JB. New evidence on the mechanisms underlying bradykinin-mediated contraction of the pig iris sphincter in vitro. Peptides 2003;24:1045-51. (Pubitemid 37130177)
40. Escribano J, Coca-Prados M. Bioinformatics and reanalysis of subtracted expressed sequence tags from the human ciliary body: Identification of novel biological functions. Mol Vis 2002;8:315-32. (Pubitemid 36153622)
41. Fernandez-Durango R, Rollin R, Mediero A, Roldan-Pallares M, Feijo JG, Sanchez JG, et al. Localization of endothelin-1 mRNA expression and immunoreactivity in the anterior segment of human eye: Expression of ETA and ETB receptors. Mol Vis 2003;9:103-9. (Pubitemid 38097574)
42. FernandezDurango R, Nunez DJR, Brown MJ. Messenger RNAs encoding the natriuretic peptides and their receptors are expressed in the eye. Exp Eye Res 1995;61:723-9. (Pubitemid 26020639)
43. Gaskin FS, Farr SA, Banks WA, Kumar VB, MorleyJE. Ghrelin-induced feeding is dependent on nitric oxide. Peptides 2003;24:913-8. (Pubitemid 37011439)
44. Geyer O, Bar-Ilan A, Nachman R, Lazar M, Oron Y. Beta(3)-adrenergic relaxation of bovine iris sphincter. Febs Lett 1998;429:356-8. (Pubitemid 28300391)
45. Gnanapavan S, Kola BBS, Morris DG, McGee P, Fairclough P, Bhattacharya S, et al. The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab 2002;86: 2988-91. (Pubitemid 34655375)
46. Goel M, Picciani RG, Lee RK, Bhattacharya SK. Aqueous humor dynamics: a review. Open Ophthalmol J 2010;4:52-9.
47. Gustafsson LE, Wiklund NP. Adenosine-modulation of cholinergic and nona-drenergic noncholinergic neurotransmission in the rabbit iris sphincter. Br J Pharmacol 1986;88:197-204. (Pubitemid 16020793)
48. Hartnett ME, Penn JS. Mechanisms and management of retinopathy of prematurity. N EnglJ Med 2012;367:2515-26.
49. Hayashi K, Masuda K. Effects of vasoactive intestinal polypeptide (vip) and cyclic-amp on the isolated sphincter pupillae muscles of the albino rabbit. Jpn J Ophthalmol 1982;26:437-42. (Pubitemid 13180732)
50. Hayashi K, Mochizuki M, Masuda K. Effects of vasoactive intestinal polypeptide (vip) and cyclic-amp on isolated dilator pupillae muscle of albino rabbit eye.JpnJ Ophthalmol 1983;27:647-54.
51. Hosoda H, Kojima M, Matsuo H, Kangawa K. Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue. Biochem Biophys Res Commun 2000;279:909-13. (Pubitemid 32042875)
52. Howard AD, Feighner SD, Cully DF, Arena JP, Liberator PA, Rosenblum CI, et al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 1996;273:974-7. (Pubitemid 26275178)
53. Hsieh MM, Linde NS, Wynter A, Metzger M, Wong C, Langsetmo I, et al. HIF prolyl hydroxylase inhibition results in endogenous erythropoietin induction, erythrocytosis, and modest fetal hemoglobin expression in rhesus macaques. Blood 2007;110:2140-7. (Pubitemid 47443933)
54. Ishizaka N, Noda M, Yokoyama S, Kawasaki K, Yamamoto M, Higashida H. Muscarinic acetylcholine receptor subtypes in the human iris. Brain Res 1998;787:344-7. (Pubitemid 28197927)
55. Kasimay O, Iseri SO, Barlas A, Bangir D, Yegen C, Arbak S, et al. Ghrelin ameliorates pancreaticobiliary inflammation and associated remote organ injury in rats. Hepatol Res 2006;36:11-9. (Pubitemid 44309288)
56. Katsanos A, Dastiridou A, Georgoulias P, Cholevas P, Kotoula M, Tsironi EE. Plasma and aqueous humour levels of ghrelin in open-angle glaucoma patients. Clin Exp Ophthalmol 2011;39:324-9.
57. Kawamura K, Sato N, Fukuda J, Kodama H, Kumagai J, Tanikawa H, et al. Ghrelin inhibits the development of mouse preimplantation embryos in vitro. Endocrinology 2003;144:2623-33. (Pubitemid 36629915)
58. Kim MS, Yoon CY, Jang PG, Park YJ, Shin CS, Park HS, et al. The mitogenic and antiapoptotic actions of ghrelin in 3T3-L1 adipocytes. Mol Endocrinol 2004;18:2291-301.
59. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999;402:656-60. (Pubitemid 129516334)
60. Kojima M, Kangawa K. Ghrelin: structure and function. Physiol Rev 2005;85:495-522. (Pubitemid 40404635)
61. Koo GC, Huang C, Camacho R, Trainor C, Blake JT, Sirotina-Meisher A, et al. Immune enhancing effect of a growth hormone secretagogue. J Immunol 2001;166:4195-201. (Pubitemid 32224953)
62. Leite-Moreira AF, Soares JB. Physiological, pathological and potential therapeutic roles of ghrelin. Drug Discov Today 2007;12:276-88. (Pubitemid 46467484)
63. Leung PK, Chow KBS, Lau PN, Chu KM, Chan CB, Cheng CHK, et al. The truncated ghrelin receptor polypeptide (GHS-R1b) acts as a dominant-negative mutant of the ghrelin receptor. Cell Signal 2007;19:1011-22. (Pubitemid 46437436)
64. Li A, Cheng G, Zhu GH, Tarnawski AS. Ghrelin stimulates angiogenesis in human microvascular endothelial cells: implications beyond GH release. Biochem Biophys Res Commun 2007;353:238-43. (Pubitemid 46014561)
65. Lu W, Okamura T, Bian K, Inatomi A, Toda N. Prostaglandins involved in contractions by angiotensin-iiand bradykinin of isolated dog sphincter pupillae. Br J Pharmacol 1988;95:544-50.
66. Maihofner C, Schlotzer-Schrehardt U, Guhring H, Zeilhofer HU, Naumann GO, Pahl A, et al. Expression of cyclooxygenase-1 and -2 in normal and glaucomatous human eyes. Invest Ophthalmol Vis Sci 2001;42:2616-24. (Pubitemid 32954872)
67. Malagon MM, Luque RM, Ruiz-Guerrero E, Rodriguez-Pacheco F, Garcia-Navarro S, Casanueva FF, et al. Intracellular signaling mechanisms mediating ghrelin-stimulated growth hormone release in somatotropes. Endocrinology 2003;144:5372-80. (Pubitemid 37476066)
68. Masuda Y, Yamahara NS, Tanaka M, Ryang S, Kawai T, Imaizumi Y, et al. Characterization of muscarinic receptors mediating relaxation and contraction in the rat iris dilator muscle. BrJ Pharmacol 1995;114:769-76.
69. Mousseaux D, Le Gallic L, Ryan J, Oiry C, Gagne D, Fehrentz JA, et al. Regulation of ERK1/2 activity by ghrelin-activated growth hormone secretagogue receptor 1A involves a PLC/PKCvarepsilon pathway. BrJ Pharmacol 2006;148:350-65. (Pubitemid 43801182)
70. Mozid AM, Tringali G, Forsling ML, Hendricks MS, Ajodha S, Edwards R, et al. Ghrelin is released from rat hypothalamic explants and stimulates corticotrophin-releasing hormone and arginine-vasopressin. Horm Metab Res 2003;35:455-9. (Pubitemid 37204560)
71. Nagaya N, Kojima M, Uematsu M,Yamagishi M, Hosoda H, Oya H, et al. Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. Am J Physiol Regul IntegrComp Physiol 2001;280, pp R1483-R7.
72. Nakahara K, Nakagawa M, Baba Y, Sato M, Toshinai K, Date Y, et al. Maternal ghrelin plays an important role in rat fetal development during pregnancy. Endocrinology 2006;147:1333-42. (Pubitemid 43244367)
73. Nanzer AM, Khalaf S, Mozid AM, Fowkes RC, Patel MV, Burrin JM, et al. Ghrelin exerts a proliferative effect on a rat pituitary somatotroph cell line via the mitogen-activated protein kinase pathway. Eur J Endocrinol 2004;151:233-40. (Pubitemid 39207019)
74. Ortego J, Coca-Prados M. Molecular identification and coexpression ofgalanin and GalR-1 galanin receptor in the human ocular ciliary epithelium: differential modulation of their expression by the activation of alpha(2)- and beta(2)-adrenergic receptors in cultured ciliary epithelial cells. J Neurochem 1998;71:2260-70. (Pubitemid 28531235)
75. Ortego J, Coca-Prados M. Functional expression of components of the natriuretic peptide system in human ocular nonpigmented ciliary epithelial cells. Biochem Biophys Res Commun 1999;258:21-8. (Pubitemid 29286995)
76. Ortego J, CocaPrados M. Molecular characterization and differential gene induction of the neuroendocrine-specific genes neurotensin, neurotensin receptor, PC1, PC2, and 7B2 in the human ocular ciliary epithelium. J Neurochem 1997;69:1829-39. (Pubitemid 27452727)
77. Osborne NN, Barnett NL. Endothelin-1 stimulates phosphatidylinositol hydrolysis in the iris ciliary complex and is a potent constrictor of the sphincter muscle. Exp Eye Res 1992;54:285-90.
78. Patterson M, Murphy KG, le Roux CW, Ghatei MA, Bloom SR. Characterization of ghrelin-like immunoreactivity in human plasma. J Clin Endocr Metab 2005;90:2205-11. (Pubitemid 40586263)
79. Pemberton CJ, Tokola H, Bagi Z, Koller A, Pontinen J, Ola A, et al. Ghrelin induces vasoconstriction in the rat coronary vasculature without altering cardiac peptide secretion. Am J Physiol Heart Circul Physiol 2004;287, pp H1522-H9.
80. Piccone M, Littzi J, Krupin T, Stone RA, Davis M, Wax MB. Effects of neuropeptide Y on the isolated rabbit iris dilator muscle. Invest Ophthalmol Vis Sci 1988;29:330-2. (Pubitemid 18057586)
81. Pierno S, De Luca A, Desaphy JF, Fraysse B, Liantonio A, Didonna MP, et al. Growth hormone secretagogues modulate the electrical and contractile properties of rat skeletal muscle through a ghrelin-specific receptor. BrJ Pharmacol 2003;139:575-84. (Pubitemid 36819627)
82. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. BrJ Ophthalmol 2006;90:262-7. (Pubitemid 43325451)
83. Raviola G, Raviola E. Intercellular junctions in the ciliary epithelium. Invest Ophthalmol Vis Sci 1978;17:958-81. (Pubitemid 8397569)
84. Rey S, Semenza GL. Hypoxia-inducible factor-1-dependent mechanisms of vascularization and vascular remodelling. Cardiovasc Res 2010;86:236-42.
85. Rocha De Sousa A, Pereira-Silva P, Azevedo-Pinto S, Rodrigues-Araujo J, Tavares-Silva M, Pinho S. Ghrelin's expression in the eye and its implication in the reduction of intraocular pressure. Acta Ophthalmol 2012;90.
86. Rocha De Sousa A, Ramos-Tavares M, Teles A, Leite-Moreira AF. Ghrelin's MRNA levels in the developing rat's eye. Acta Ophthalmol 2008;86.
87. Rocha-Sousa A, Alves-Faria P, Falcao-Pires I, Falcao-Reis F, Leite-Moreira AF. Analyses of aqueous humour ghrelin levels of eyes with and without glaucoma. BrJ Ophthalmol 2009;93:131-2.
88. Rocha-Sousa A, Falcao-Reis F, Leite-Moreira AF. The obestatin/ghrelin system as a novel regulatory mechanism of iris muscle contraction. Curr Eye Res 2008;33:73-9. (Pubitemid 351156948)
89. Rocha-Sousa A, Saraiva J, Henriques-Coelho T, Falcao-Reis F, Correia-Pinto J, Leite-Moreira AF. Ghrelin as a novel locally produced relaxing peptide of the iris sphincter and dilator muscles. Exp Eye Res 2006;83:1179-87. (Pubitemid 44397038)
90. Rocha-Sousa AA, Tavares-Silva M, Pereira-Silva P, Azevedo-Pinto S, Rodrigues-Araújo J, Pinho S, et al. Ghrelin is expressed in the ciliary body and presents a significant and sustained hypotensive effect in acute glaucoma models. Invest Ophthalmol Vis Sci 2012. E-abstract.
91. Rossi F, Castelli A, Bianco MJ, Bertone C, Brarna M, Santiemma V. Ghrelin induces proliferation in human aortic endothelial cells via ERK1/2 and PI3K/Akt activation. Peptides 2008;29:2046-51.
92. Sapieha P, Hamel D, Shao Z, Rivera JC, Zaniolo K, Joyal JS, et al. Proliferative retinopathies: angiogenesis that blinds. IntJ BiochemCell Biol 2010;42:5-12.
93. Smith LE, Wesolowski E, McLellan A, Kostyk SK, D'Amato R, Sullivan R, et al. Oxygen-induced retinopathy in the mouse. Invest Ophthalmol Vis Sci 1994;35:101-11. (Pubitemid 24046832)
94. Soares JB, Rocha-Sousa A, Castro-Chaves P, Henriques-Coelho T, Leite-Moreira AF. Inotropic and lusitropic effects of ghrelin and their modulation by the endocardial endothelium, NO, prostaglandins, GHS-R1a and K-Ca channels. Peptides 2006;27:1616-23. (Pubitemid 43866262)
95. Stamer WD, Piwnica D, Jolas T, Carling RW, Cornell CL, Fliri H, et al. Cellular basis for bimatoprost effects on human conventional outflow. Invest Ophthalmol Vis Sci 2010;51:5176-81.
96. Tachado SD, Akhtar RA, Abdellatif AA. Activation of beta-adrenergic receptors causes stimulation of cyclic-amp, inhibition of inositol trisphosphate, and relaxation of bovine iris sphincter smooth-muscle - biochemical and functional interactions between the cyclic-amp and calcium signaling systems. Invest Ophthalmol Vis Sci 1989;30:2232-9. (Pubitemid 19259929)
97. Tachado SD, Akhtar RA, Zhou CJ, Abdellatif AA. Effects of isoproterenol and forskolin on carbachol-induced and fluoroaluminate-induced polyphosphoinositide hydrolysis, inositol trisphosphate production, and contraction in bovine iris sphincter smooth-muscle - interaction between camp and ip3 2nd messenger systems. Cell Signal 1992;4:61-75.
98. Tajti J, Uddman R, Moller S, Sundler F, Edvinsson L. Messenger molecules and receptor mRNA in the human trigeminal ganglion. J Auton Nerv Syst 1999;76:176-83. (Pubitemid 29322040)
99. Tamm E, Flugel C, Stefani FH, RohenJW. Contractile cells in the human scleral spur. Exp Eye Res 1992;54:531-43.
100. Toda M, Okamura T, Fujimiya M, Azuma I, Toda N. Mechanisms underlying the neurogenic relaxation of isolated porcine sphincter pupillae. Exp Eye Res 1999;68:505-12. (Pubitemid 29185444)
101. Tschop M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature 2000;407:908-13.
102. Tschop M, Wawarta R, Riepl RL, Friedrich S, Bidlingmaier M, Landgraf R, et al. Post-prandial decrease of circulating human ghrelin levels. J Endocrinol Invest 2001;24:RC19-21. (Pubitemid 32573786)
103. Uchikawa Y, Okano M, Sawada A, Asada Y, Kobayashi H, Wada A, et al. Relaxant effect of adrenomedullin on bovine isolated iris sphincter muscle under resting conditions. Clin Exp Pharmacol Physiol 2005;32:675-80. (Pubitemid 41025831)
104. Ueda N, Muramatsu I, Sakakibara Y, Fujiwara M. Non-cholinergic, nona-drenergic contraction and substance-p in rabbit iris sphincter muscle. Jpn J Pharmacol 1981;31:1071-9. (Pubitemid 12140369)
105. Wan Z, Woodward DF, Cornell CL, Fliri HG, Martos JL, Pettit SN, et al. Bimatoprost, prostamide activity, and conventional drainage. Invest Ophthalmol Vis Sci 2007;48:4107-15. (Pubitemid 351261036)
106. Wang H, Byfield G, Jiang Y, Smith GW, McCloskey M, Hartnett ME. V.E.G.F-mediated STAT3 activation inhibits retinal vascularization by down-regulating local erythropoietin expression. Am J Pathol 2012;180:1243-53.
107. Wang L, Chen Q, Li G, Ke D. Ghrelin stimulates angiogenesis via GHSR1a-dependent MEK/ERK and PI3K/Akt signal pathways in rat cardiac microvascular endothelial cells. Peptides 2012;33:92-100.
108. Wang ZY, Alm P, Hakanson R. Distribution and effects of pituitary adenylate cyclase-activating peptide in the rabbit eye. Neuroscience 1995;69:297-308.
109. Wiederholt M, Sturm A, Lepple-Wienhues A. Relaxation of trabecular mesh-work and ciliary muscle by release of nitric oxide. Invest Ophthalmol Vis Sci 1994;35:2515-20. (Pubitemid 24137048)
110. Xu X, Jhun BS, Ha CH, Jin ZG. Molecular mechanisms of ghrelin-mediated endothelial nitric oxide synthase activation. Endocrinology 2008;149:4183-92.
111. Yamaji K, Yoshitomi T, Usui S. Effect of somatostatin andgalanin on isolated rabbit iris sphincter and dilator muscles. Exp Eye Res 2003;77:609-14. (Pubitemid 37188736)
112. Yamaji K, Yoshitomi T, Usui S, Ohnishi Y. Mechanical properties of the rabbit iris smooth muscles. Vis Res 2003;43:479-87. (Pubitemid 36106469)
113. Yoshitomi T, Yamaji K, Ishikawa H, Ohnishi Y. Effect of pituitary adenylate cyclase-activating peptide on isolated rabbit iris sphincter and dilator muscles. Invest Ophthalmol Vis Sci 2002;43:780-3. (Pubitemid 34184497)
114. Yousufzai SY, Abdel-Latif AA. Calcitonin gene-related peptide relaxes rabbit iris dilator smooth muscle via cyclic AMP-dependent mechanisms: crosstalk between the sensory and sympathetic nervous systems. Curr Eye Res 1998;17:197-204. (Pubitemid 28073786)
115. Yousufzai SYK, Ali N, Abdel-Latif AA. Effects of adrenomedullin on cyclic AMP formation and on relaxation in iris sphincter smooth muscle. Invest Ophthalmol Vis Sci 1999;40:3245-53.
116. Zaniolo K, Sapieha P, Shao Z, Stahl A, Zhu T, Tremblay S, et al. Ghrelin modulates physiologic and pathologic retinal angiogenesis through GHSR-1a. Invest Ophthalmol Vis Sci 2011;52:5376-86.
117. Zhang Q, Huang WD, Lv XY, Yang YM. Ghrelin protects H9c2 cells from hydrogen peroxide-induced apoptosis through NF-kappa B and mitochondria-mediated signaling. Eur J Pharmacol 2011;654: 142-9.
118. Zhang SQ, Butler JM, Ohara K, Cole DF. Sensory neural mechanisms in contraction of the isolated sphincter pupillae - the role for substance-p and the effects of sensory denervation on the responses to miotics. Exp Eye Res 1982;35:43-54. (Pubitemid 12044415)
119. Zhang SQ, Butler JM, Ohara K, Cole DF. Sensory neural mechanisms in contraction of the isolated sphincter pupillae: the role for substance P and the effects of sensory denervation on the responses to miotics. Exp Eye Res 1982;35:43-54. (Pubitemid 12044415)