Identification of the ghrelin-GHSR 1 system and its influence in the modulation of induced ocular hypertension in rabbit and rat eyes.
Recent studies evidenced a decrease in ghrelin's aqueous humor levels in patients with glaucoma. The goal of our investigation was to study the effect of the ghrelin-GHSR-1a system in the modulation of intraocular pressure in acute ocular hypertension models and its expression and distribution in ocular tissues. Two animal models of acute ocular hypertension were used to study the effect of the ghrelin-GHSR-1a system in the modulation of intraocular pressure: the rabbit and the rat. Ocular hypertension was induced by an intravitreal injection of 20% NaCl. Ghrelin or des-acyl ghrelin were delivered subconjunctivally and the intraocular pressure was assessed by a rebound tonometer that was calibrated for each species. In addition, we have studied the influence of nitric oxide and prostaglandins on ghrelin's effect in the rabbit animal model. Finally, we determined by immunofluorescence the expression of ghrelin and GHSR-1 in the rat's ocular tissue. Ghrelin decreased the intraocular pressure in both animal models (maximum decrease: 43.8±12.0% in the rabbit and 29.0±7.46% in the rat). In the rabbit, this effect was blunted in the presence of l-NAME and ketorolac. Des-acyl ghrelin only decreased the intraocular pressure in the rat (maximum decrease: 34.9±8.15%). Ghrelin expression was detected in the ciliary processes and GHSR-1 expression was detected in the trabecular meshwork and ciliary body. The ghrelin-GHSR-1 system is expressed in the anterior segment of the eye. Ghrelin and des-acyl ghrelin are responsible for a hypotensive effect in acute ocular hypertension animal models.
Department of Sense Organs, Faculty of Medicine, University of Porto, Porto, Portugal; Department of Ophthalmology, São João Hospital, Porto, Portugal. Electronic address: arsousa@med.up.pt.
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Rocha-Sousa
Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal.
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Pereira-Silva
Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal.
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Tavares-Silva
Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal.
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Azevedo-Pinto
Department of Ophthalmology, São João Hospital, Porto, Portugal.
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Rodrigues-Araújo
Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal.
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Pinho
Department of Experimental Biology, Faculty of Medicine, University of Porto, Porto, Portugal; IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal.
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Avelino
Department of Sense Organs, Faculty of Medicine, University of Porto, Porto, Portugal; Department of Ophthalmology, São João Hospital, Porto, Portugal.
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Falcão-Reis
Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal.
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Leite-Moreira
D000818:Animals; D002923:Cilia / Q000378:metabolism; D005123:Eye / Q000378:metabolism / Q000473:pathology; D054439:Ghrelin / Q000096:biosynthesis* / Q000235:genetics; D005901:Glaucoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007429:Intraocular Pressure / Q000235:genetics; D009798:Ocular Hypertension / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D011817:Rabbits; D051381:Rats; D054440:Receptors, Ghrelin / Q000096:biosynthesis* / Q000235:genetics; D012965:Sodium Chloride / Q000633:toxicity; D014129:Trabecular Meshwork / Q000378:metabolism
D054439:Ghrelin; C571124:Ghsr1a protein, rat; D054440:Receptors, Ghrelin; D012965:Sodium Chloride
Des-acyl ghrelin; GHSR-1a; Ghrelin; Intraocular pressure