title: The elevation of intraocular pressure is associated with apoptosis and increased immunoreactivity for nitric oxide synthase in rat retina whereas the effectiveness of retina derived relaxing factor is unaffected.
abstract: Glaucoma is a progressive ocular disease that stands in the upper rank for the cause of blindness in worldwide. In the present study, we aimed to elucidate the possible disturbances occurred in the layers of retina due to an increase in intraocular pressure (IOP) and to verify the effectiveness of retina derived relaxing factor, i.e., RRF in this pathologic condition. The increase in IOP was induced by cauterization of the three of episcleral veins simultaneously in rats. After 8 weeks period, the retinas excised from the vein cauterized eyes were evaluated for the possible histopathological and ultrastructural alterations as well as for the relaxing effects on isolated bovine retinal and rat mesenteric arteries, in comparison with the retinas obtained from contralateral sham-operated eyes. In the retinas of IOP-elevated eyes, profound morphological deteriorations were determined in the ganglion and outer nuclear cell layers which were associated with an increased number of TUNEL positive cells in the ganglion and inner nuclear cell layers. Increased immunohistochemical stainings for three isoforms of nitric oxide synthase (NOS) were defined in almost all layers of the retinas of IOP-elevated eyes, in which eNOS was abundant particularly in the inner plexiform and ganglion cell layers. An irregular basal folding of retinal pigment epithelium (RPE) and an increased inter lamellar space of photoreceptor cell layer furtherly characterized the prominent degeneration of those layers in the retinas of IOP-elevated eyes. On the other hand, the relaxing effects of the retina obtained from IOP-elevated eyes were determined to be unchanged on the retinal and mesenteric arteries precontracted either with prostaglandin F2α (PGF2α, 30 μM) or potassium chloride (K(+), 100 mM), when compared with the relaxations of control retina obtained from contralateral sham-operated eyes. Overall, these findings suggested that the elevation of IOP induces prominent structural changes in rat retina particularly in the ganglion and inner layers that is associated with marked apoptosis and increased immunoreactivity for NOS, while the functional effectiveness of retina derived relaxing factor, i.e., RRF is unaffected.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey; Department of Medical Pharmacology, Section of Internal Medical Sciences, Faculty of Medicine, Giresun University, Giresun, Turkey. Electronic address: selcuk_takir@yahoo.com.
authors.forename: Selçuk
authors.initials: S
authors.lastname: Takır
authors.affiliation: Department of Biology, Faculty of Science, Istanbul University, Istanbul, Turkey.
authors.forename: Ebru
authors.initials: E
authors.lastname: Gürel-Gürevin
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey.
authors.forename: Ayça
authors.initials: A
authors.lastname: Toprak
authors.affiliation: Department of Biology, Faculty of Science, Istanbul University, Istanbul, Turkey.
authors.forename: Cihan
authors.initials: C
authors.lastname: Demirci-Tansel
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey.
authors.forename: B Sönmez
authors.initials: BS
authors.lastname: Uydeş-Doğan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004195:Disease Models, Animal; D005901:Glaucoma / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D007429:Intraocular Pressure / Q000502:physiology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D009798:Ocular Hypertension / Q000209:etiology / Q000503:physiopathology*; D051381:Rats; D012160:Retina / Q000187:drug effects / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D012165:Retinal Ganglion Cells / Q000473:pathology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D019001:Nitric Oxide Synthase
keywords: Apoptosis; Glaucoma; Intraocular pressure; Mesenteric artery; NOS; Retina; Retinal artery; Retinal relaxing factor