cyclic-gmp and Myopia

This study aimed to investigate the expression of N-methyl-D-aspartate receptor 1 (NMDAR1) and neuronal constitutive nitric oxide synthase (ncNOS) during form-deprivation myopia (FDM). FDM models were established in guinea pigs with facemasks. NMDAR1 expression in the retina was detected by immunohistochemistry and Western blot analysis. ncNOS mRNA expression was examined by in situ hybridization. cGMP content was measured by radioimmunoassay. In control group, NMDAR1 and ncNOS were expressed in binocular retinas, and there was no significant difference in NMDAR1 and ncNOS expression and cGMP content between the two eyes. However, NMDAR1 and ncNOS expression and cGMP content in the retina of FDM eyes were significantly higher than that of contralateral untreated eyes. Furthermore, ncNOS mRNA level and cGMP content was highly correlated. In conclusion, FDM upregulates the expression of NMDAR1 and ncNOS and increases cGMP content in the retina. NMDAR1/NO-cGMP pathway may contribute to abnormal visual signals during myopic progression.

Topics: Animals; Cyclic GMP; Disease Models, Animal; Disease Progression; Guinea Pigs; Myopia; Nitric Oxide Synthase Type I; Receptors, N-Methyl-D-Aspartate; Retina; Transcriptional Activation

Development of myopia is associated with remodeling of the sclera, a tissue composed principally of collagen. Cyclic guanosine monophosphate (cGMP) regulates collagen synthesis in several organs; therefore, we investigated the effects of soluble guanylyl cyclase (sGC) stimulation and inhibition on refraction and ocular growth in guinea pigs under normal and form-deprived (FD) conditions.. Retinal and scleral cGMP concentrations were measured in normal and monocularly FD guinea pigs at 2 days, 1 week, and 2 weeks of form deprivation and following 2 days recovery. Stimulation of sGC by BAY41-2272 and inhibition by NS-2028 were achieved by daily subconjunctival injection in normal and FD eyes. Refraction and axial parameters were measured at the commencement, middle, and cessation of the experiment. cGMP levels were also determined at the end of the experiment.. Retinal and scleral cGMP concentrations increased in FD eyes from 2 days to 2 weeks (P ≤ 0.029). Levels decreased after 2 days of recovery (P ≤ 0.003). Daily injections of BAY41-2272 induced a myopic shift (P ≤ 0.001) and ocular elongation (P ≤ 0.01) in normal animals, but did not alter myopia in FD eyes (P > 0.05). In contrast, daily injections of NS-2028 partially reduced myopic shifts (P ≤ 0.012) and ocular elongation (P ≤ 0.015) induced by form deprivation, but did not affect ocular growth and refraction in normal eyes (P > 0.05). Retinal and scleral cGMP levels were increased by BAY41-2272 in normal eyes and decreased by NS-2028 in FD eyes.. Changes in cGMP signaling contribute to myopic development. Thus, cGMP may be a potential therapeutic target for preventing/treating myopia.

Topics: Animals; Collagen; Conjunctiva; Cyclic GMP; Disease Progression; Eye; Guanylate Cyclase; Guinea Pigs; Injections; Myopia; Oxadiazoles; Oxazines; Radioimmunoassay; Retina; Sclera; Sensory Deprivation

To investigate the mechanism of myopia following intravitreous injection of MK801 (dizocipine maleate) intravitreous injected.. Three-week-old guinea pigs were divided into six groups: group A (control), group B (3 weeks form-deprivation in right eye), group C ( 3 weeks form-deprivation in right eye + saline), group D (3 weeks form-deprivation in right eye + MK801 1ng), group E (3 weeks form-deprivation in right eye + MK801 10 ng), group F (3 weeks form-deprivation in right eye + MK801 100 ng). The refraction and axial length of the eyes were measured. ncNOS was measured by hybridization in situ, and cyclic GMP (cGMP) concentrations by radioimmunochemistry. The correlation between MK801 concentration and diopter degree, axial length of the eyes, and levels of ncNOS or cyclic GMP were analyzed with linear correlation in the groups C-F.. Diopter degree was decreased, axial eye length was shorted and levels of ncNOS and c-GMP were decreased in groups C, D, E and F dependent on the concentration of MK801. The diopter degree had positive correlation with MK801 concentration (r=0.702, P<0.05), while the axial eye length and the levels of ncNOS and cGMP were negatively correlated (r=-0.736, -0.637, -0.725, P<0.05). MK801 injected into the vitreous humor can restrain myopia by down-regulated the expression of the nitric oxide-cyclic GMP signaling pathway. The effect is concentration dependent.

Topics: Animals; Cyclic GMP; Dizocilpine Maleate; Down-Regulation; Female; Form Perception; Guinea Pigs; Injections, Intraocular; Male; Myopia; Nitric Oxide Synthase Type I; Sensory Deprivation; Signal Transduction; Vitreous Body

To explore the expression of cyclic guanine monophosphate (cGMP) and the ultrastructure change in retina of guinea pig with form-deprivation myopia and the underlying mechanisms.. Three-weeks-old guinea pigs were distributed in 3 groups: an untreated group (Group I), a myopia 2-weeks group (Group II) and a myopia 3-weeks group (Group III), animals underwent monocular form-deprivation by facemask for 2 and 3 weeks. The right eyes were deprived and the left eyes were self-controlled. The refraction and axial length of the eyes was measured. Retina was observed by electron microscope. The expression of cGMP was detected by radioimmunochemistry.. Deprived eyes in guinea pig showed significant development of myopia, the refraction and axial length was increased. The pathological changes in ultrastructure of retina were aggravated with the development of myopia. The expression of cGMP was significantly up-regulated in the deprived eyes compared with self-control eyes(P<0.05).. Form-deprivation can up-regulate the expression of cyclic GMP, which might play an important role in the development of myopia.

Topics: Animals; Cyclic GMP; Disease Models, Animal; Female; Guinea Pigs; Male; Myopia; Random Allocation; Retina; Sensory Deprivation; Vision, Monocular

The aim of this study was to investigate the time-course change of nitric oxide synthase (NOS) activity and cyclic GMP (cGMP) concentration in the posterior retina, choroid and sclera after differing periods of form-deprivation in guinea pigs. Three groups of guinea pigs were subjected to monocular FD for 7, 14 or 21 days. NOS activity and cGMP concentrations in ocular tissues of FD eyes and control eyes were analyzed by radioimmunoassay. The presence of NOS isoforms was detected by immunohistochemistry. Guinea pigs presented with considerable myopia after 14 days of FD. Retinal NOS activity in the FD group was lower than in the control group after 7 days of FD and was higher than in the control group after 14 and 21 days of FD. The choroidal and scleral NOS activities in the FD groups were higher than in the control groups after 21 days. The cGMP concentrations in the FD groups were higher than in the control groups at 21 days of the retinal, choroidal, and scleral tissues. Furthermore, the retinal cGMP concentration in the FD group was also significantly elevated at 14 days relative to the control group. We detected expression of three NOS isoforms in guinea pig ocular tissues. Our main observations were a change in NOS activity and an up-regulation in cGMP concentrations in posterior ocular tissues during the development of myopia. The function of elevated NOS activity may be mediated by cGMP.

Topics: Animals; Choroid; Cyclic GMP; Disease Models, Animal; Form Perception; Gene Expression Regulation; Guinea Pigs; Isoenzymes; Myopia; Nitric Oxide; Nitric Oxide Synthase; Random Allocation; Retina; Sclera; Second Messenger Systems; Sensory Deprivation; Signal Transduction; Time Factors

The form deprivation (FD) reduces spatial contrasts and induces myopia. Nitric oxide and cyclic guanosine monophosphate (cGMP) are involved in visual signal transmission. This study investigated changes in nitric oxide synthase (NOS) activity and cGMP concentration in ocular tissues in acute and chronic form deprivation myopia.. Guinea pigs had one eye covered by translucent glass for 7, 14 or 21 days. Untreated litter mates were used as controls. NOS activity and cGMP concentrations in the retinal, choroidal and scleral tissues of FD eyes and control eyes were analyzed by radioimmunoassay after various durations of FD. The expression of NOS subtypes was identified by immunohistochemistry.. Myopia was successfully induced in FD eyes after 14 days. Compared with control groups, the retinal NOS activity and cGMP concentrations in the FD eyes significantly increased after 14 and 21 days while the retinal NOS activity in the FD eyes was transiently suppressed by 7 days of FD. The NOS activity and cGMP concentrations of choroid and sclera in the FD eyes were higher than in the control groups at 21 days. The three isoenzymes of nitric oxide synthase were detected in the ocular tissues of guinea pigs.. The NOS activity and cGMP concentrations were upregulated after chronic FD and the retinal NOS activity was transiently suppressed at acute FD. The function of elevated NOS activity may be mediated by cGMP.

Topics: Animals; Cyclic GMP; Guinea Pigs; Immunohistochemistry; Myopia; Nitric Oxide; Nitric Oxide Synthase; Refractive Errors; Retina