cyclic-gmp and Retinal-Detachment

Topics: Aqueous Humor; Calcium; Cataract; Cornea; Cyclic GMP; Eye; Glaucoma; Intraocular Pressure; Lens, Crystalline; Ocular Physiological Phenomena; Optics and Photonics; Photoreceptor Cells; Pigment Epithelium of Eye; Retina; Retinal Detachment; Retinal Pigments; Rod Cell Outer Segment

The present experiments show that IFNgamma receptors are mainly localized to the basolateral membrane of human retinal pigment epithelium (RPE). Activation of these receptors in primary cultures of human fetal RPE inhibited cell proliferation and migration, decreased RPE mitochondrial membrane potential, altered transepithelial potential and resistance, and significantly increased transepithelial fluid absorption. These effects are mediated through JAK-STAT and p38 MAPK signaling pathways. Second messenger signaling through cAMP-PKA pathway- and interferon regulatory factor-1-dependent production of nitric oxide/cGMP stimulated the CFTR at the basolateral membrane and increased transepithelial fluid absorption. In vivo experiments using a rat model of retinal reattachment showed that IFNgamma applied to the anterior surface of the eye can remove extra fluid deposited in the extracellular or subretinal space between the retinal photoreceptors and RPE. Removal of this extra fluid was blocked by a combination of PKA and JAK-STAT pathway inhibitors injected into the subretinal space. These results demonstrate a protective role for IFNgamma in regulating retinal hydration across the outer blood-retinal barrier in inflammatory disease processes and provide the basis for possible therapeutic interventions.

Topics: Absorption; Adult; Animals; Biological Transport; Body Fluids; Cell Movement; Cell Proliferation; Cells, Cultured; Choroid; Cyclic AMP; Cyclic GMP; Cystic Fibrosis Transmembrane Conductance Regulator; Fetus; Humans; Interferon gamma Receptor; Interferon Regulatory Factor-1; Interferon-gamma; Janus Kinases; Membrane Potentials; Mitochondria; p38 Mitogen-Activated Protein Kinases; Rats; Receptors, Interferon; Retinal Detachment; Retinal Pigment Epithelium; Second Messenger Systems; STAT Transcription Factors; Tissue Distribution

Earlier studies have revealed a decreased level of cGMP in vitreous fluid obtained from patients with a retinal detachment. To further investigate this phenomenon, we developed an experimental retinal detachment model in pigs.. Experimental unilateral retinal detachments were induced in pig eyes by subretinal injection of 0.25% sodium hyaluronate. Fourteen days later the vitreous and retinas were analyzed for cGMP expression. Following enucleation, the retinas were incubated in the presence of a nonselective phosphodiesterase inhibitor (IBMX), and the particulate guanylyl cyclase stimulator atrial natriuretic peptide (ANP) or the soluble guanylyl cyclase stimulator sodium nitroprusside (SNP). cGMP was visualized in retinal wholemounts by immunochemistry combined with a computer based stereology system. cGMP levels in vitreous were determined by ELISA.. The mean vitreous cGMP level in pig eyes with a retinal detachment (1.45 pmol/ml) was significantly lower compared to the mean level of cGMP in healthy pig eyes (4.61 pmol/ml; p=0.028 was considered significant). In the inner retina, ANP as well as SNP induced cGMP immunoreactivity in both detached and healthy retinas. After incubation with ANP, cGMP could also be detected in the outer nuclear layer of the detached retina, whereas this was not the case in the normal retina.. Experimental retinal detachment in the pig eye leads to a decrease of cGMP levels in vitreous similar to that observed in clinical studies. This model may be helpful to analyze the mechanisms involved in cGMP dynamics following retinal detachment.

Topics: Animals; Cyclic GMP; Female; Immunohistochemistry; Photoreceptor Cells, Vertebrate; Retina; Retinal Detachment; Swine; Vitreous Body

Cyclic guanosine monophosphate (cGMP) is produced in different retinal cells, including photoreceptor cells, wherein cGMP mediates photo-transduction. CGMP is degraded by phosphodiesterases (PDE). The aim was to investigate whether retinal detachment alters intraocular cGMP levels in human eyes.. cGMP and PDE were determined in vitreous fluid from 50 eyes with a retinal detachment (group I) and in 20 control samples (group II) of vitreous fluid from eyes without retinal detachment. Group III consisted of subretinal fluid samples from 70 eyes with retinal detachment.. cGMP in vitreous fluid from eyes with retinal detachment (6.5 (SD 1.7) nM) was decreased compared to controls (67.1 (10.0) nM) (p<0.0001). In subretinal fluid, the mean level of cGMP was 2.4 (0.2) nM. No PDE could be detected in any of the intraocular fluid samples of patients nor controls. A decrease in the mean level of cGMP in subretinal fluid of eyes with retinal detachment correlated with a longer duration of detachment (r = -0.45, p = 0.007).. Retinal detachment was found to be associated with a decrease in vitreous cGMP concentration. In subretinal fluid, a low cGMP level correlated inversely with the duration of the detachment.

Topics: Adolescent; Adult; Aged; Aqueous Humor; Case-Control Studies; Cyclic GMP; Female; Humans; Male; Middle Aged; Phosphoric Diester Hydrolases; Retinal Detachment; Scleral Buckling; Vitrectomy; Vitreous Body

Levels of cAMP (23.1 pmol/ml) and cGMP (22.6 pmol/ml) are nearly equal in normal rabbit vitreous, although aqueous cAMP levels (29.9 pmol/ml) are 10 times higher than aqueous cGMP levels (2.6 pmol/ml) (P < 0.01). Intravitreal cAMP values decrease slightly 1 week after vitrectomy and lensectomy and return to normal whether the retina is attached, detached, or surgically removed. In contrast, intravitreal cGMP levels are profoundly depressed at 7 days (approximating normal aqueous levels) and are more than 50% lower than normal 30-42 days after surgery. The presence of these cyclic nucleotides in intraocular fluid and their responsiveness after surgery may signify a potential regulatory role in the physiologic responses of the eye to retinal detachment and its repair.

Topics: Animals; Aqueous Humor; Cataract Extraction; Cyclic AMP; Cyclic GMP; Female; Male; Rabbits; Retinal Detachment; Vitrectomy; Vitreous Body

Topics: Body Fluids; Cyclic AMP; Cyclic GMP; Eye Proteins; Humans; Protein Kinases; Retinal Detachment; Time Factors