Advances in the research of plant-derived natural products against retinoblastoma.

Retinoblastoma (RB) is a highly aggressive ocular tumor, and due to socioeconomic and medical constraints, many children receive treatment only in the metaphase and advanced clinical stages, resulting in high rates of blindness and disability. Although several approaches exist in the treatment of RB, some children with the disease do not have satisfactory results because of various factors. Plant-derived natural products have shown definite therapeutic effects in the treatment of various tumors and are also widely used in the study of RB. We review plant-derived natural products used in the study of anti-RB to provide ideas for the clinical application of these drugs and the development of new therapeutic drugs.

Effect of Andrographis paniculata polysaccharide on human retinoblastoma Y79 cell proliferation and apoptosis.

AIM: To explore the effect of the Andrographis paniculata (A. paniculata) polysaccharide on the proliferation and apoptosis of human retinoblastoma (RB) Y79 cells and its mechanism. METHODS: The refined A. paniculata polysaccharide was obtained using techniques such as water extraction, ethanol precipitation, and decompression concentration. The inhibition effect of the A. paniculata polysaccharide on the proliferation of Y79 cells was detected by cell proliferation assay. Flow cytometry was used for the detection of cell apoptosis rate and cycle change. Real-time qunatitative polymerase chain reaction (RT qPCR)and Western blotting were used to detect the expression of cell apoptosis signal pathway-related factors (caspase-3, caspase-8, and caspase-9) and cell cycle signal pathway-related factors (CDK1 and cyclinB1) at the transcriptional and translational levels. RESULTS: Infrared and ultraviolet spectrum scanning showed that the extracted drug was a polysaccharide with high purity. After being treated with different concentrations of A. paniculata polysaccharide for different periods of time, the Y79 cells showed different degrees of proliferation inhibition. Flow cytometric observations showed that the cell apoptosis rate and the proportion of cells blocked in the G2/M phase were significantly increased after A. paniculata polysaccharide treatment. Further analysis revealed that the mRNA and protein expression of caspase-3, caspase-8, and caspase-9 in the A. paniculata polysaccharide treatment groups increased significantly compared with that in the control groups, while the expression of CDK1 and cyclinB1 decreased significantly. CONCLUSION: The A. paniculata polysaccharide could inhibit the proliferation and induce apoptosis of Y79 cells. Its possible mechanism is via the upregulation of caspase-3, caspase-8, and caspase-9 expression in the cell apoptotic signaling pathway and the downregulation of CDK1 and cyclinB1 expression in the cell cycle signaling pathway.

Anti-proliferation and apoptosis-inducing effects of sodium aescinate on retinoblastoma Y79 cells.

AIM: To investigate the anti-proliferation and apoptosis-inducing effects of sodium aescinate (SA) on retinoblastoma Y79 cells and its mechanism. METHODS: Y79 cells were cultured at different drug concentrations for different periods of time (24, 48, and 72h). The inhibitory effect of SA on proliferation of Y79 cells was detected by the cell counting kit-8 (CCK-8) assay, and the morphology of Y79 cells in each group was observed under an inverted microscope. An IC50 of 48h was selected for subsequent experiments. After pretreatment with SA for 24 and 48h, cellular DNA distribution and apoptosis were detected by flow cytometry. Real-time qunatitative polymerase chain reaction (RT-qPCR) and Western blot were used to assess changes in related genes (CDK1, CyclinB1, Bax, Bcl-2, caspase-9, caspase-8, and caspase-3). RESULTS: SA inhibited proliferation and induced apoptosis of Y79 cells in a time-dependent and concentration-dependent manner. Following its intervention in the cell cycle pathway, SA can inhibit the expression of CDK1 and CyclinB1 at the mRNA and protein levels, and block cells in the G2/M phase. In caspase-related apoptotic pathways, up-regulation of Bax and down-regulation of Bcl-2 caused caspase-9 to self-cleave and further activate caspase-3. What's more, the caspase-8-mediated extrinsic apoptosis pathway was activated, and the activated caspase-8 was released into the cytoplasm to activate caspase-3, which as a member of the downstream apoptotic effect group, initiates a caspase-cascade reaction that induces cell apoptosis. CONCLUSION: SA inhibits the proliferation of Y79 cells by arresting the cell cycle at the G2/M phase, and induces apoptosis via the caspase-related apoptosis pathway, indicating that SA may have promising potential as a chemotherapeutic drug.

Incidence of myopia and biometric characteristics of premyopic eyes among Chinese children and adolescents.

BACKGROUND: To determine the one-year incidence and progression rates of myopia and its association with baseline ocular biometric parameters in school-based samples of children and adolescents in China. METHODS: Two thousand four hundred thirty two grade 1 and 2346 grade 7 students living in the southwest part of China participated in the baseline survey. After 1 year, 2310 (95.0%) grade 1 and 2191 (93.4%) grade 7 students attended the follow-up examination. Refractive error was measured after cycloplegia using the same autorefractor and by the same optometrists in the baseline and follow-up examination. Myopia was defined as spherical equivalent of less than - 0.50 diopter. RESULTS: The overall one-year incidence of myopia was 33.6% (95% confidence interval [CI]: 31.7-35.5) among grade 1 students and 54.0% (95% CI: 51.5-56.5) for grade 7 students. The one-year myopia progression rate was - 0.97 D (95% CI: -1.22 to - 0.71) in grade 1 students and - 1.02 D (95% CI: -1.07 to - 0.96) in grade 7 students. Per mm increase in baseline axial lengths increased the risk of myopia onset by 28% among grade 1 students and 22% among grade 7 students after 1 year. The incidence rates of myopia were found to be higher in grade 7 students with thinner premyopic lenses. CONCLUSIONS: The incidence and progression rates of myopia were very high in Chinese children and adolescents in recent years. Premyopic eyes were characterized with longer axial lengths and thinner lenses. These data had considerable implications for formulating myopia prevention strategies in China.

Study on the possible factors leading to complications of hydroxyapatite orbital implantation / 国际眼科杂志(Guoji Yanke Zazhi)

·Hydroxyapatite ( HA ) orbital implant has been widely used since it was developed due to its many advantages. It is one of the ideal materials to fill the orbital volume after enucleation or evicseration. However, it still causes complications, and some complications such as severe eye exposure may require reimplant surgery. The paper reviews the clinical application of HA orbital implant, the possible factors leading to complications of HA orbital implantation and the treatments for several common complications. The review aims to provide some help to readers.

In vivo monitoring of VEGF-induced retinal damage in the Kimba mouse model of retinal neovascularization.

PURPOSE: To monitor retinal and vascular changes associated with neovascularization, which were generated through photoreceptor-specific overexpression of human vascular endothelial growth factor (hVEGF), in transgenic trVEGF029 (Kimba) mice. MATERIALS AND METHODS: The Spectralis Heidelberg Retina Angiography and Optical Coherence Tomography (HRA+OCT) imaging device was used to track changes in the retina and retinal vasculature of Kimba mouse eyes (n = 32) and control C57Bl/6J mouse eyes (n = 20) at 4, 8, 12, 16, and 20 weeks of age. RESULTS: Retinal vascular leakage, focal dilated vessel, vessel tortuosity, attenuated vessel, venous beading, capillary dropout, retinal non-perfusion, neovascularization, and focal retinal detachment were observed in Kimba mouse eyes. Through track changes, we detected edema in the peripheral part of the retina of 2/32 Kimba mouse eyes examined. The retinae of the Kimba mice were significantly thinner than control mice retinae at all ages of the mice assessed (p < 0.01). CONCLUSIONS: In vivo monitoring of retinal vascular and neural retinal changes in the Kimba mice using the Spectralis HRA+OCT imaging device allowed us to assess and track VEGF-induced damages in great detail and in real-time. Real-time monitoring of these changes can be used to study the interplay between VEGF overexpression and other molecular factors and to monitor dynamic retinal changes following therapeutic intervention.

Characterization of a mouse model of hyperglycemia and retinal neovascularization.

One of the limitations of research into diabetic retinopathy is the lack of suitable animal models. To study how the two important factors--hyperglycemia and vascular endothelial growth factor--interact in diabetic retinopathy, the Akimba mouse (Ins2AkitaVEGF+/-) was generated by crossing the Akita mouse (Ins2Akita) with the Kimba mouse (VEGF+/+). C57Bl/6 and the parental and Akimba mouse lines were characterized by biometric measurements, histology, immunohistochemistry, and Spectralis Heidelberg retinal angiography and optical coherence tomography. The Akimba line not only retained the characteristics of the parental strains, such as developing hyperglycemia and retinal neovascularization, but developed higher blood glucose levels at a younger age and had worse kidney-body weight ratios than the Akita line. With aging, the Akimba line demonstrated enhanced photoreceptor cell loss, thinning of the retina, and more severe retinal vascular pathology, including more severe capillary nonperfusion, vessel constriction, beading, neovascularization, fibroses, and edema, compared with the Kimba line. The vascular changes were associated with major histocompatibility complex class II+ cellular staining throughout the retina. Together, these observations suggest that hyperglycemia resulted in higher prevalences of edema and exacerbated the vascular endothelial growth factor-driven neovascular and retinal changes in the Akimba line. Thus, the Akimba line could become a useful model for studying the interplay between hyperglycemia and vascular endothelial growth factor and for testing treatment strategies for potentially blinding complications, such as edema.

Spontaneous rodent models of diabetes and diabetic retinopathy.

Diabetes is a complex and heterogeneous disorder presently affecting more than 100 million people worldwide and causing serious socio-economic problems. Spontaneous rodent models of diabetes mellitus have proved invaluable in understanding the pathogenesis, complications, and genetic or environmental influences that increase the risks of diabetes. We have reviewed here in the development and characterization of spontaneous rodent models that displayed most features commonly associated with diabetic retinopathy.

VEGF expression and cell apoptosis in NOD mouse retina.

AIM: To investigate retinal vascular endothelial growth factor (VEGF) level and retinal cells apoptosis in the early stage of diabetic NOD mouse retina. METHODS: Animals were divided into non-diabetes group, (control) (2-, 4-, 6-, 8- and 12-week sub-groups, n=30) and diabetes group (2-, 4-, 6-, 8- and 12-week sub-groups, n=30). Enzyme-linked immunosorbent assay (ELISA) was performed to detect VEGF level in both serum and retina. Transmission electron microscope method was used to examine retinal cell apoptosis. RESULTS: Compared with the control group, VEGF levels in serum and retina were increased significantly in the NOD group (12 weeks: 4.9±0.4µg/g vs 0.19±0.1µg/g in serum sample, P<0.01; 165±9µg/g vs 17±5µg/g in retinal sample, P<0.01). There exists a positive correlation between serum VEGF and retinal VEGF levels in the early diabetic NOD mice (γ=0.9902, P=0.001). The number of the cells apoptosis in the ganglion cells and endothelium can also been found increased significantly in the NOD group (P<0.01). CONCLUSION: The high VEGF expression may be contributed to increased retinal cells apoptosis. Many factors associated with retinal VEGF expression might involve in the early diabetes stage.

Effect of intravitreal bevacizumab injection before vitrectomy on proliferative diabetic retinopathy.

AIM: To evaluate the effect of intravitreal bevacizumab (IVB) injection 1 week before pars plana vitrectomy (PPV) in proliferative diabetic retinopathy (PDR) patients. METHODS: A retrospective research was done on 46 PDR patients who were divided into PPV group (n=28) and IVB group (n=18, PPV with preoperative IVB). Bevacizumab was injected 1 week before PPV. Main outcome measures were visual acuity, incidence of iatrogenic retinal breaks, intraoperative and postoperative bleeding. RESULTS: At 1 month after surgery, visual acuity in PPV (82.1%) and IVB group (88.9%) improved significantly (P<0.01) and the difference between the two groups was not significant (P>0.05). Iatrogenic retinal breaks were reported in 18 cases (64.3%) in PPV group and 4 cases (22.2%) in IVB group (P<0.05). Intraoperative bleeding was encountered in all cases in PPV group and 7 cases (39%) in IVB group (P<0.01). Postoperative bleeding was reported in 9 cases (32.1%) in PPV group and none in IVB group (P<0.01). CONCLUSION: IVB injection before PPV is helpful in reducing iatrogenic retinal breaks, intraoperative and postoperative bleeding in PDR patients.

[Study on the interaction of luteolin with human serum albumin by fluorescence quenching method].

The interaction between luteolin and human serum albumin (HSA) was studied by using fluorescence quenching spectra, synchronous fluorescence spectra and ultra-violet spectra. The results showed that luteolin had a strong ability to quench the fluorescence of HAS The Stern-Volmer curve of the fluorescence quenching of HSA by luteolin indicated that the mechanism behind the quenching between luteolin and HSA was a static quenching. According to the Forster theory of non-radiation energy transfer, the binding distances (r) and the binding constants (KA) were calculated. The thermodynamic parameters showed that the interaction between luteolin and HSA was driven mainly by hydrophobic force. Synchronous spectra were used to investigate the conformational changes of HSA.

Interaction of tetrandrine with human serum albumin: a fluorescence quenching study.

The interaction of tetrandrine with human serum albumin (HSA) was studied by measuring fluorescence quenching spectra, synchronous fluorescence spectra and ultra-violet spectra. The fluorescence quenching spectra of HSA in the presence of tetrandrine showed that tetrandrine quenched the fluorescence of HSA. The quenching constants of tetrandrine on HSA were determined using the Stern-Volmer equation. Static quenching and non-radiation energy transfer were the two main reasons leading to the fluorescence quenching of HSA by tetrandrine. According to the Förster theory of non-radiation energy transfer, the binding distances (r) and the binding constants (K(A)) were obtained. The thermodynamic parameters obtained in this study revealed that the interaction between tetrandrine and HSA was mainly driven by a hydrophobic force. The conformational changes of HSA were investigated by synchronous spectrum studies.