text: 2.2.
  Iris and Ciliary Body
  Serotonin is present in mammalian iris-ciliary body complex (ICB) at higher concentration that in non-mammalian species [5, 45, 73, 129, 137]. Moreover, the presence of serotonergic nerves has been demonstrated in studies conducted on the ICB of various species [102, 137, 138]. Experimental evidence and radioligand analyses have defined the presence at this level of three different types of serotonin receptors [10, 28, 85, 136, 137], i.e. 5-HT1A, 5-HT2A/2C and 5-HT7 [98], one linked to a stimulation of inositol phosphates (5-HT2 subtype), while the others two are linked to cAMP activity.
  The plausibility of the existence of more than one 5-HT receptor type in the ciliary body is confirmed by intraocular pressure (IOP) experiments. Topical application of serotonin has been reported to both elevate [84] and lower [88] IOP in rabbit. A large number of reports have shown that serotonin agonists and antagonists can produce increases and decreases in IOP when given orally, topically to the eye or when they are directly injected in the anterior chamber [10, 26, 34, 35, 64, 75, 84, 87, 88, 112, 113, 126, 136, 137]. A rationale for such apparently contradictory results may be due to the different sites of action, i.e. which class of serotonin receptor is activated. In fact, in rabbit the administration of 5-methyl-urapidil (a combined 5-HT1A agonist/alpha1 adrenoreceptor antagonist) and 8-OH-DPAT (8-hydroxydypropylaminotetralin, a 5HT1A agonist) reduces IOP, while the administration of 5-CT (5-carboxamidotryptamine, a 5-HT1A and 5-HT7 agonist) increases IOP [36, 84, 99].
  Chidlow, Le Corre and Osborne [28] have recently demonstrated that, in section taken through the whole eye and ciliary body, prominent 5-HT1A and 5-HT7 receptor messenger ribonucleic acid signals were obtained. These signals were evident in both the pigmented and non-pigmented epithelial cell layers of the pars plicata region of the ciliary processes, but not in the pars plana or in the ciliary musculature. 5-HT1A and 5-HT7 signals were apparent in the posterior processes but not in the iris processes. The presence of both receptors in the ciliary body would certainly provide an explanation for the shallow displacement curves observed in [3H]5-HT binding studies with the tissue [110], since this ligand can be used to label both receptors. Because the ciliary epithelium of the pars plicata is responsible for the secretion of aqueous humor, an obvious function for these two receptors would be an involvement in the control of aqueous production and, consequently, of the IOP level. Further, the almost identical distribution of the 5-HT1A and 5-HT7 messengers ribonucleic acid indicate that the receptors may be co-localized in epithelial cells. The presence of two serotonin receptors with opposing effects on cAMP in the same cell layer prompts the suggestion that they could act antagonistically. The agonism of 5-HT1A receptors, negatively coupled to cAMP, reduces IOP by decreasing the production of aqueous humor, like beta-receptor antagonists which, diminishing the content of cAMP at the postjunctional site, lowers the aqueous humor secretion with a consequent decrease in IOP [98]. On the contrary, the administration of 5-CT induces a rise in IOP, which is partly or entirely caused by an increase in aqueous humor secretion mediated by 5-HT7 receptors [84].
  The other type of serotonin receptor present in the ICB is a 5-HT2 type. Serotonin stimulates the accumulation of inositol phosphates in the ICB and this effect is partially counteracted by the 5-HT2 antagonists ketanserin, methysergide and mianserin [98]. Studies with ketanserin have demonstrated that, when orally or topically applied, it lowers IOP in animals, healthy volunteers and in glaucomatous patients [26, 34, 37, 64, 75, 88, 113, 126]. It has been emphasized that ketanserin also possesses an affinity for alpha1-adrenoreceptors [27, 36, 139], and for this reason the effects of ketanserin on IOP may not be entirely caused by its action on 5-HT2 receptors. However, data from human studies conducted after oral or topical administration of ketanserin, in which were determined the variations of IOP, total outflow facility and pupil diameter, demonstrated that the alpha1-adrenoreceptor blocking effect exerted by ketanserin should represent a further aspect of its mechanism of action, probably due to a functional sharing of these receptors [64, 87]. Lastly, already in 1992 Martin and co-workers showed the occurrence of a significant correlation between the content of serotonin in the aqueous humor and IOP in the human eye [85].
  In 1981, Moro and his collaborators found that intravitreal injection of 5, 6-dihydroxytryptamine, a serotonergic neurotoxin, causes miosis [91]. The identification of 5-HT7, but not of 5-HT1 receptors in the rabbit iris, suggests that this population of serotonergic receptors is involved in the relaxation of the sphincter of the pupil. In fact, one of the function correlate to 5-HT7 receptor activation includes smooth muscle relaxation observed in a variety of isolated tissue preparations, in which elevation of cAMP concentration was also detected [3, 44]. Further evidence for the mediation of the relaxant response via the 5-HT7 receptor is provided by the localization of messenger ribonucleic acid transcripts encoding the 5-HT7 receptor in many blood vessels [67]. This hypothesized mechanism of action is also supported by the fact that various other receptor types, also positively coupled to cAMP, in the iris cause relaxation of the sphincter muscle [1, 28].
  
entities.text: ['Ciliary Body']
entities.type: Multi-tissue_structure
entities.entity_id: PMC-2701282-sec-04_T1
entities.text: ['Iris']
entities.type: Multi-tissue_structure
entities.entity_id: PMC-2701282-sec-04_T2
entities.text: ['iris-ciliary body complex']
entities.type: Multi-tissue_structure
entities.entity_id: PMC-2701282-sec-04_T3
entities.text: ['nerves']
entities.type: Multi-tissue_structure
entities.entity_id: PMC-2701282-sec-04_T5
entities.text: ['ICB']
entities.type: Multi-tissue_structure
entities.entity_id: PMC-2701282-sec-04_T4
entities.text: ['ICB']
entities.type: Multi-tissue_structure
entities.entity_id: PMC-2701282-sec-04_T6
entities.text: ['ciliary body']
entities.type: Multi-tissue_structure
entities.entity_id: PMC-2701282-sec-04_T7
entities.text: ['intraocular']
entities.type: Immaterial_anatomical_entity
entities.entity_id: PMC-2701282-sec-04_T8
entities.text: ['anterior chamber']
entities.type: Multi-tissue_structure
entities.entity_id: PMC-2701282-sec-04_T9
entities.text: ['eye']
entities.type: Organ
entities.entity_id: PMC-2701282-sec-04_T10
entities.text: ['ciliary body']
entities.type: Multi-tissue_structure
entities.entity_id: PMC-2701282-sec-04_T11
entities.text: ['epithelial cell']
entities.type: Cell
entities.entity_id: PMC-2701282-sec-04_T12
entities.text: ['pars plicata']
entities.type: Multi-tissue_structure
entities.entity_id: PMC-2701282-sec-04_T13
entities.text: ['ciliary']
entities.type: Multi-tissue_structure
entities.entity_id: PMC-2701282-sec-04_T14
entities.text: ['pars plana']
entities.type: Multi-tissue_structure
entities.entity_id: PMC-2701282-sec-04_T15
entities.text: ['ciliary musculature']
entities.type: Multi-tissue_structure
entities.entity_id: PMC-2701282-sec-04_T16
entities.text: ['iris']
entities.type: Multi-tissue_structure
entities.entity_id: PMC-2701282-sec-04_T17
entities.text: ['ciliary body']
entities.type: Multi-tissue_structure
entities.entity_id: PMC-2701282-sec-04_T18
entities.text: ['tissue']
entities.type: Tissue
entities.entity_id: PMC-2701282-sec-04_T19
entities.text: ['ciliary epithelium']
entities.type: Tissue
entities.entity_id: PMC-2701282-sec-04_T20
entities.text: ['pars plicata']
entities.type: Multi-tissue_structure
entities.entity_id: PMC-2701282-sec-04_T21
entities.text: ['ICB']
entities.type: Multi-tissue_structure
entities.entity_id: PMC-2701282-sec-04_T22
entities.text: ['ICB']
entities.type: Multi-tissue_structure
entities.entity_id: PMC-2701282-sec-04_T23
entities.text: ['pupil']
entities.type: Multi-tissue_structure
entities.entity_id: PMC-2701282-sec-04_T24
entities.text: ['eye']
entities.type: Organ
entities.entity_id: PMC-2701282-sec-04_T25
entities.text: ['iris']
entities.type: Multi-tissue_structure
entities.entity_id: PMC-2701282-sec-04_T26
entities.text: ['sphincter']
entities.type: Tissue
entities.entity_id: PMC-2701282-sec-04_T27
entities.text: ['pupil']
entities.type: Multi-tissue_structure
entities.entity_id: PMC-2701282-sec-04_T28
entities.text: ['smooth muscle']
entities.type: Tissue
entities.entity_id: PMC-2701282-sec-04_T29
entities.text: ['tissue']
entities.type: Tissue
entities.entity_id: PMC-2701282-sec-04_T30
entities.text: ['blood vessels']
entities.type: Multi-tissue_structure
entities.entity_id: PMC-2701282-sec-04_T31
entities.text: ['iris']
entities.type: Multi-tissue_structure
entities.entity_id: PMC-2701282-sec-04_T32
entities.text: ['sphincter muscle']
entities.type: Tissue
entities.entity_id: PMC-2701282-sec-04_T33
entities.text: ['epithelial cells']
entities.type: Cell
entities.entity_id: PMC-2701282-sec-04_T34
entities.text: ['eye']
entities.type: Organ
entities.entity_id: PMC-2701282-sec-04_T35
entities.text: ['humor']
entities.type: Organism_substance
entities.entity_id: PMC-2701282-sec-04_T37
entities.text: ['humor']
entities.type: Organism_substance
entities.entity_id: PMC-2701282-sec-04_T38
entities.text: ['humor']
entities.type: Organism_substance
entities.entity_id: PMC-2701282-sec-04_T39
entities.text: ['cell']
entities.type: Cell
entities.entity_id: PMC-2701282-sec-04_T40