1.MK801 controls form-deprivation myopia by nitric oxide-cyclic GMP signaling pathway in guinea pig.
Dan WEN ; Shuangzhen LIU ; Junfeng MAO ; Xingping TAN ; Chaohua XIA ; Chunan YIN
Journal of Central South University(Medical Sciences) 2012;37(7):737-742
OBJECTIVE:
To investigate the mechanism of myopia following intravitreous injection of MK801 (dizocipine maleate) intravitreous injected.
METHODS:
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.
RESULTS:
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)
CONCLUSION
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.
Animals
;
Cyclic GMP
;
metabolism
;
Dizocilpine Maleate
;
administration & dosage
;
pharmacology
;
Down-Regulation
;
Female
;
Form Perception
;
physiology
;
Guinea Pigs
;
Injections, Intraocular
;
Male
;
Myopia
;
physiopathology
;
Nitric Oxide Synthase Type I
;
metabolism
;
Sensory Deprivation
;
physiology
;
Signal Transduction
;
drug effects
;
Vitreous Body
;
drug effects
2.Near-infrared fluorescent zinc-dipicolylamine: a new molecular imaging probe to monitor the efficiency of chemotherapy.
Shuo HU ; Wenwen CHAI ; Zhiguo LIU ; Chunan YIN ; Meng LEI
Journal of Central South University(Medical Sciences) 2011;36(8):760-764
OBJECTIVE:
To investigate the feasibility of a novel molecular probe of Zn-DPA-PSS794 to monitor the efficiency of doxorubicin to ovarian cancer and compare with Cy5.5-annexin V.
METHODS:
Efficiency of doxorubicin to OVCAR-8 cells in vitro was measured by MTT assay and flow cytometry. The in vivo studies were performed on an OVCAR-8 xenograft tumor model. Mice were divided into a control group and a treatment group. Each group was divided into 2 subgroups, DPA and annexin V. In the treatment group, the mice were treated with doxorubicin for 2 doses. All mice were performed optical imaging by Zn-DPA-PSS794 or Cy5.5-annexin V, respectively and then sacrificed. The tumor was separated and stained by HE. The expression of caspase-3 protein was measured by Western blot.
RESULTS:
The IC50 of doxorubicin to OVCAR-8 was 6 μmol/L. The percentage of apoptosis and dead cells was 35% after doxorubicin treatment. In the optical image, photons accumulated in the tumor either by Zn-DPA-PSS794 or Cy 5.5-annexin V in the treatment group. That was negative in the control group. The fluorescence intensity had significant difference between the 2 groups(P<0.001). The nuclei were big and stained with deep color after the cells were stained with HE. The caspase-3 expression was high in the treatment group, while it was low in the control group.
CONCLUSION
Zn-DPA-PSS794 as a probe used by optical imaging can monitor the efficiency of doxorubicin to OVCAR-8 xenograft tumor, which is similar to Cy5.5-annexin V.
Animals
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Apoptosis
;
drug effects
;
Carbocyanines
;
Cell Line, Tumor
;
Doxorubicin
;
pharmacology
;
Female
;
Fluorescent Dyes
;
Humans
;
Infrared Rays
;
Mice
;
Mice, Nude
;
Molecular Imaging
;
Organometallic Compounds
;
Ovarian Neoplasms
;
pathology
;
Picolines
;
Spectroscopy, Near-Infrared
;
methods
3.Expression of cyclic guanine monophosphate and the ultrastructure change in retina of guinea pig with form-deprivation myopia.
Dan WEN ; Shuangzhen LIU ; Junfeng MAO ; Xingping TAN ; Chaohua XIA ; Chunan YIN
Journal of Central South University(Medical Sciences) 2011;36(3):249-253
OBJECTIVE:
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.
METHODS:
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.
RESULTS:
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).
CONCLUSION
Form-deprivation can up-regulate the expression of cyclic GMP, which might play an important role in the development of myopia.
Animals
;
Cyclic GMP
;
metabolism
;
Disease Models, Animal
;
Female
;
Guinea Pigs
;
Male
;
Myopia
;
etiology
;
metabolism
;
pathology
;
Random Allocation
;
Retina
;
metabolism
;
ultrastructure
;
Sensory Deprivation
;
Vision, Monocular
;
physiology