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As a secreted glycoprotein with a molecular weight of 50kDa, pigment epithelial-derived factor(PEDF)was originally found to be secreted by pigment epithelial cells; afterwards, it was found to be widely distributed in various organs and tissues throughout the body and played multiple biological roles. In recent years, a large number of studies have confirmed that PEDF can initiate a wide range of cellular responses in eye tissues by binding with a variety of receptors, which has the functions of regulating angiogenesis, anti-inflammatory, antioxidant stress and neurotrophic. Recent studies have found that the application of exogenous PEDF has a preferable therapeutic effect on the repair of dry eye and corneal injury. In addition, the PEDF gene encoding therapy has shown promising in the treatment of age-related macular degeneration and diabetic retinopathy. This review mainly summarizes the potential therapeutic effects and limitations of pigment epithelium-derived factors in dry eye, corneal injury, age-related macular degeneration, diabetic retinopathy and other diseases in recent years, which provides help for further research on the diagnosis and treatment of ocular diseases with PEDF.
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@#AIM: To investigate the protective effect of the antioxidant N-acetylcysteine(NAC)on retina in early diabetic rats. <p>METHODS: Thirty healthy adult male SD rats were randomly assigned to the normal control group(CON group, <i>n</i>=10)and the diabetes group(DM group, <i>n</i>=20). After fasting for 12h, the DM group was injected with 1% streptozotocin(STZ)solution, according to 60mg/kg disposable left lower abdominal injection. After 72h, blood was taken from the rat tail vein to detect blood glucose, diabetic model animals were defined as ≥16.7mmol/L. Model rats were randomly divided into diabetes control group(group D)and NAC treatment group(group N). After the model was established, N group of rats were injected with 4μL 1.6μg/μL NAC through the vitreous cavity every week. Rats in CON group and D group were injected with 4μL 0.01mmol/L phosphate buffer saline. All the rats no diet water, group feeding. Body mass and blood glucose were recorded weekly. After the diabetes was modeled, 2mo killed the experimental animals. The thickness of the inner layer of the retina of rats in each group was determined by HE staining. The number of retinal ganglion cells and the level of pigment epithelial derived factor in the retina were measured by immunofluorescence.<p>RESULTS: The thickness of retinal kernel layer increased in group N compared with group D(<i>P</i><0.01), and there was no difference between group CON and group(<i>P</i>>0.05). Compared with CON group, the number of retinal ganglion cells decreased in group D(<i>P</i><0.01), and decreased slightly in group N(<i>P</i>>0.05). Retinal ganglion cells decreased in group D compared with group N(<i>P</i><0.01). Compared with CON group, PEDF expression decreased in group D(<i>P</i><0.01), and decreased slightly in group N(<i>P</i>>0.05). The expression of PEDF in group D decreased compared with group N(<i>P</i><0.01).<p>CONCLUSION: The protective effect of antioxidant NAC on retinal tissue in early diabetic rats may be due to the up-regulation of PEDF levels in the retina.
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Objective: To study the effects of pigment epithelial-derived factor (PEDF) on the proliferation, apoptosis and invasion of squamous lung carcinoma cells in high-glucose environment so as to explore the significance of PEDF in the development, prognosis and treatment of lung cancer associated with diabetes. Methods: SK-MES-1 lung squamous carcinoma cells were cultured and divided into negative control group; high-glucose group; and PEDF+high glucose groups 1, 2 and 3. The cell morphological changes were observed under the inverted microscope. Then proliferation inhibition rates of SK-MES-1 cells in all the groups were observed by MTT assay. The cell cycle and cell apoptosis rates were detected by flow cytometry. The number of penetration cells was determined by cell invasion experiment. Expression of VEGF in culture supernatant in each group was detected by ELISA. Results: ① Compared with that in the negative control group, the proliferation inhibition rate and apoptosis rate in high-glucose group were low, the percentage of cells blocked in G0/G1 phase was decreased, the number of penetration cells was increased and the concentration of VEGF was increased (P<0.05). ② With the increase of PEDF intervention concentration, the proliferation inhibition rate and apoptosis rate in each group increased, the percentage of G0/G1 phase increased, the number of penetration cells decreased, and the concentration of VEGF decreased (P<0.05). Conclusion: ① The development of squamous cell carcinoma of the lung is promoted in high glucose. ② PEDF can inhibit the proliferation of lung squamous cell carcinoma cells in high-glucose environment, promote early apoptosis and reduce the invasiveness in the concentration-dependent manner. PEDF is predicted to be a target therapeutic drug for lung cancer complicated with diabetes mellitus.
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Objective To investigate the protective effects of intravitreal injection of pigment epithelial-derived factor (PEDF) gene-modified human umbilical cord mesenchymal stem cells (PEDF-MSCs) on the pathological changes in retinal tissue of diabetic rats.Methods hUCMSCs were isolated from human umbilical cord tissue using tissue culture methods,and transfected with lentiviral vectors at a infection multiplicity of 50.Then diabetic model in rats was successfully induced by intraperitoneal injection of streptozotocin.And the rats were divided into normal control (N),PBS treatment (D1),hUCMSCs treatment (D2) and PEDF-MSC treatment (D3) group according to different treatment methods.Three months after modeling,treatment began in D1,D2 and D3 group,but N group left untreated.Two weeks after treatment,the expression of PEDF-MSCs in the eye of rats was detected by fluorescence microscopy,and HE staining was performed to observe the changes in retinal structure and the full-thickness of the retina in each group.Results The expression of CD105,CD73,CD90 was observed,while the expression of CD34,CD45,CD11b,CD19 and HLA-DR did not present.After 2 weeks of treatment,it was in the vitreous cavity not the retina that clusters of red fluorescence appeared in D2 group with fluorescence microscope.There were clusters of green fluorescence in the vitreous cavity not in the retina of D3 group.HE staining showed that the retina had intact structure and clear layers as well as neatly arranged and stained evenly cells in N group.In D1 group,the nerve fibers layer (NFL) showed obvious edema,the blood vessels were dilated,the inner plexiform layer (IPL) were loose and the inner nuclear layer (INL) cells were disordered.In D2 group,the edema of NFL relieved.In D3 group,NFL edema was significantly alleviated,and the cells of INL and outer nuclear layer (ONL) arranged in regular.Full-thickness of retina was (103.82 ±4.15) μm in N group,(138.86 ±4.71) μm in D1 group,(131.17 ±3.89) μm in D2 group,and (112.24 ±4.22) μm in D3 group,respectively,and the differences were statistically significant (all P ＜ 0.05).Conclusion PEDF-MSCs can survive and continue to express in the vitreous cavity of diabetic rats for a long time.Meanwhile,intravitreal injection of PEDF-MSCs can ameliorate retinal edema and the retinal injury in diabetic rats.
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Background Diabetic retinopathy (DR) seems to be rarely found in high myopia patients with diabetes mellitus.This finding suggests that myopia,especially high myopia,plays a protective effect against DR.It is well-known that the primary pathological base of DR is neovescularization,and the changes of vascular endothelial growth factor (VEGF) and pigment epithelium derived factor (PEDF) are associated with DR.Objective This study was to analyze the expressions of VEGF and PEDF in retina and investigate the influence of high myopia on the pathogenesis of DR.Methods Forty-eight 3-day-old guinea pigs were randomly divided into normal control group,high myopia group,diabetic group and diabetes with high myopia group.Translucent goggles were worn in the right eyes of the guinea pigs for consecutive 8 weeks to induce high myopia,and streptozocin (STZ) was intraperitoneally injected at a dose of 60 mg/kg for four times,every three days for once,to establish diabetic models in the corresponding groups.Twelve weeks after modeling,the animals were sacrificed by excessive anesthesia,and the retinas were isolated for the histopathological examination.Expressions of VEGF and PEDF in the retinas were detected by immunohistochemistry.The use and care of experimental animals conformed to Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.Results The diopter of the normal control group,high myopia group,diabetic group and diabetes with high myopia group were (+0.25±0.07),(-7.50±0.04),(+0.25±0.03) and (-7.50±0.02) D,the fasting glucose of the four groups were (5.3 ±0.1),(5.1 ±0.2),(19.7 ±0.4) and (18.5±0.3)mmol/L,respectively.Compared with the normal control group,the retinas of high myopia group were thin,and the ganglion cells were less.The retinas of diabetic group were loose and oedematous.The retinas of diabetes with high myopia group were thin and oedematous.The expressing level of VEGF in retinas (absorbance value,A) were 128.61 ±5.57,118.24±2.59,155.60±9.70 and 135.15±5.22 in the normal control group,high myopia group,diabetic group and diabetes with high myopia group,respectively,showing a significant difference among the groups (F=17.365,P=0.032),and the VEGF level was significantly lower in the diabetes with high myopia group than that of the diabetic group (t =5.210,P＜0.05).The expressing level of PEDF in retinas (A value) were 145.57± 8.35,149.54±6.20,127.71±2.45 and 137.53±7.38,in the normal control group,high myopia group,diabetic group and diabetes with high myopia group,respectively,with a statistically significant difference among the four groups (F =19.210,P =0.019),and the PEDF level was significantly higher in the diabetes with high myopia group than that of the diabetic group (t=4.521,P＜0.05).Conclusions The expression of VEGF is downregulated and PEDF is upregulated in the retinas of diabetes with high myopia guinea pigs,which may be an accountable mechanism for the low incidence of DR in high myopia eyes.