Pembrolizumab for choroidal metastases from non-small cell lung cancer: a case report and literature review.

We described a 65-year-old male with choroidal metastases (CM) from non-small cell lung cancer (NSCLC). Pembrolizumab (Keytruda) combined with pemetrexed and capecitabine achieved excellent outcomes. After two cycles of pembrolizumab and chemotherapy, blurred vision and left eye pain were significantly relieved. Imaging and ophthalmologic examinations demonstrated complete resolution of the CM, as well as reduction of pulmonary shadow. CM from NSCLC shows complete and durable response to pembrolizumab and chemotherapy. We suggesting that immunotherapy combined with chemotherapy is a promising treatment for CM from NSCLC.

Modified viscocanalostomy in the Chinese population with open angle glaucoma: a 10-year follow-up results.

AIM: To study the long-term efficacy and safety of modified viscocanalostomy in Chinese people with open angle glaucoma (OAG). METHODS: This retrospective study included a total of 100 eyes from 100 Chinese patients with medically uncontrolled OAG. All the patients underwent modified viscocanalostomy with injection of viscoelastic material in the surgically created ostia of Schlemm's canal (SC). The modifications included peeling of the inner wall of SC and the juxtacanalicular meshwork, use of mitomycin C, and loosely suturing the superficial scleral flap. Intraocular pressure (IOP), visual acuity, number of medications, laser goniopuncture data and complications were recorded. The definition of complete (qualified) success was an IOP equal to or lower than 21, 18, 16 mm Hg without (with or without) anti-glaucoma medications. RESULTS: The mean IOP was 33.5±9.9 mm Hg before surgery, 15.2±3.6 mm Hg (mean IOP reduction of 51%) at 5y after surgery, and 15.6±2.8 mm Hg (mean IOP reduction of 49.9%) at 10y after surgery (P<0.001). The number of anti-glaucoma medications dropped from 2.39±0.5 preoperatively to 0.47±0.8 at 5y and 0.67±0.8 at 10y postoperatively (P<0.001). The follow-up period was 104.5±37.0mo. The qualified success rate for an IOP of 21, 18 or 16 mm Hg or less was 84% [95% confidence interval (CI): 0.80-0.88], 73% (95%CI: 0.68-0.78), and 59% (95%CI: 0.52-0.66) after 5y, and 80% (95%CI: 0.76-0.84), 69% (95%CI: 0.64-0.74), 51% (95%CI: 0.44-0.58) after 10y, respectively. There was a relationship between age, preoperative IOP and success rate (P<0.01, P<0.05). A total of 31 eyes (31.3%) in 31 patients underwent laser goniopuncture, decreasing the IOP from 22.9±4.3 mm Hg to 16.3±2.5 mm Hg (P<0.01). Neither blebitis nor endophthalmitis occurred. CONCLUSION: Modified viscocanalostomy could be performed to lower IOP, decrease multiple anti-glaucoma drops use as well. It's a safe procedure with less complications over 10y in Chinese individuals with OAG.

Activation of Nrf2/HO-1 pathway protects retinal ganglion cells from a rat chronic ocular hypertension model of glaucoma.

OBJECTIVE: The objective of this work was to find out the effects of nuclear factor erythroid 2-related factor/heme oxygenase-1 (Nrf2/HO-1) pathway on retinal ganglion cell (RGC) injury in glaucoma. METHODS: The chronic ocular hypertension (COH) rat models of glaucoma were constructed, and intraocular pressure (IOP) and RGC numbers were detected at different time points. Additionally, rats were divided into normal group (normal control rats), model group (COH model rats), and model + tBHQ group (COH model rats treated with Nrf activator, tBHQ). RGC apoptosis was detected by using TUNEL staining, and the expressions of Nrf2/HO-1 were detected by qRT-PCR and western blotting. RESULTS: COH model rats showed significant IOP elevation and the increased mRNA and protein expressions of Nrf2 and HO-1 from 1 to 6 weeks after operation, with the evidently decreased RGC numbers at 4 weeks and 6 weeks after operation (all P < 0.05). Besides, rats in the model group had increased apoptosis index (AI) of RGCs and the elevated mRNA and protein expressions of Nrf2/HO-1 with remarkably reduced RGC numbers when compared with normal control rats, but the model rats treated with tBHQ exhibited an apparent decrease in AI of RGCs, as well as remarkable increases in RGC numbers and the mRNA and protein expression of Nrf2/HO-1 (all P < 0.05). CONCLUSION: Activation of Nrf2/HO-1 pathway significantly reduced the apoptosis and injury of RGCs in rats with chronic ocular hypertension (COH), thereby protecting RGCs in glaucoma, which could be a promising clinical target to prevent RGC degeneration in glaucoma.

NKILA inhibition protects retinal pigment epithelium cells from hypoxia by facilitating NFκB activation.

Sustained retinal hypoxia causes injuries to retinal pigment epithelium (RPE) cells. We studied expression and potential functions of nuclear factor-κB (NFκB) Interacting LncRNA (NKILA) in hypoxia-treated RPE cells. Hypoxia induced NKILA expression, NKILA-IκBα association and NFκB activation in ARPE-19 cells and primary human RPE cells. shRNA-mediated knockdown of NKILA facilitated NFκB activation, inhibiting RPE cell death and apoptosis. Conversely, exogenous overexpression of NKILA blocked hypoxia-induced NFκB activation, thereby exacerbating RPE cell apoptosis. Further studies show that hypoxia downregulated microRNA-103 (miR-103), the anti-NKILA microRNA, in RPE cells. Transfection of miR-103 mimic blocked hypoxia-induced NKILA expression to significantly boost NFκB activation, protecting RPE cells from hypoxia. Collectively, we conclude that hypoxia-induced NKILA expression negatively regulates NFκB to promote RPE cell death. Conversely, NKILA inhibition protects RPE cells from hypoxia by facilitating NFκB activation.

Viscocanalostomy combined with trabeculotomy and mitomycin C in the treatment of primary congenital glaucoma.

AIM: To evaluate the long-term outcome of viscocanalostomy combined with trabeculotomy and mitomycin C in the treatment of primary congenital glaucoma. METHODS: This is a retrospective study. Forty-two eyes of 26 patients with primary congenital glaucoma were enrolled. Intraocular pressure (IOP), corneal diameter (mm) and cup/disc (C/D) were measured before and after the surgery respectively. Follow-up period was 30mo. RESULTS: The mean preoperative IOP was 30.6±7.35 mm Hg. Of the 42 eyes, 2 eyes were required conversion to trabeculectomy for the absence of Schlemm's canal. Of remained 40 eyes, 38 eyes (95%) achieved successful IOP control. The average postoperative IOP was 11.69±4.18 mm Hg at 12mo. The mean reduction was 18.91 mm Hg (P<0.0001). Eighteen (75%) eyes presented a reduction in corneal diameter, and 25 (62.5%) eyes presented a C/D ratio reversal after the surgery. There was no serious complication in any patients over the follow-up period. CONCLUSION: Viscocanalostomy combined with trabeculotomy and mitomycin C is useful in the management of primary congenital glaucoma.

Paeoniflorin Suppressed High Glucose-Induced Retinal Microglia MMP-9 Expression and Inflammatory Response via Inhibition of TLR4/NF-κB Pathway Through Upregulation of SOCS3 in Diabetic Retinopathy.

Diabetic retinopathy (DR) is a serious-threatening complication of diabetes and urgently needed to be treated. Evidence has accumulated indicating that microglia inflammation within the retina plays a critical role in DR. Microglial matrix metalloproteinase 9 (MMP-9) has an important role in the destruction of the integrity of the blood-retinal barrier (BRB) associated with the development of DR. MMP-9 was also considered important for regulating inflammatory responses. Paeoniflorin, a monoterpene glucoside, has a potent immunomodulatory effect on microglia. We hypothesized that paeoniflorin could significantly suppress microglial MMP-9 activation induced by high glucose and further relieve DR. BV2 cells were used to investigate the effects and mechanism of paeoniflorin. The activation of MMP-9 was measured by gelatin zymography. Cell signaling was measured by western blot assay and immunofluorescence assay. High glucose increased the activation of MMP-9 in BV2 cells, which was abolished by HMGB1, TLR4, p38 MAPK, and NF-κB inhibition. Phosphorylation of p38 MAPK induced by high glucose was decreased by TLR4 inhibition in BV2 cells. Paeoniflorin induced suppressor of cytokine signaling 3 (SOCS3) expression and reduced MMP-9 activation in BV2 cells. The effect of paeoniflorin on SOCS3 was abolished by the TLR4 inhibitor. In streptozotocin (STZ)-induced diabetes mice, paeoniflorin induced SOCS3 expression and reduced MMP-9 activation. Paeoniflorin suppressed STZ-induced IBA-1 and IL-1ß expression and decreased STZ-induced high blood glucose level. In conclusion, paeoniflorin suppressed high glucose-induced retinal microglia MMP-9 expression and inflammatory response via inhibition of the TLR4/NF-κB pathway through upregulation of SOCS3 in diabetic retinopathy.

Influence of the hypothalamic arcuate nucleus on intraocular pressure and the role of opioid peptides.

BACKGROUND: An opioid peptide neuron/humoral feedback regulation might be involved in changes of intraocular pressure (IOP). The aims of this study are to investigate the effects of arcuate nucleus (ARC) and opioid peptides on intraocular pressure (IOP). METHODS: Fifty-four healthy purebred New Zealand white rabbits (108 eyes) were randomly divided into 4 groups, including control group, electrical stimulation group, [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO) group, and [D-Pen 2, D-Pen5]- enkephalin (DPDPE) group. Bilateral IOP was measured after unilateral electrical stimulation of the ARC or unilateral microinjection into the ARC of the selective µ-opioid receptor agonist DAMGO or the selective δ opioid receptor agonist DPDPE, both alone and after pre-administration of either the non-selective opioid receptor antagonist naloxone or saline. RESULTS: Both electrical stimulation in ARC and micro-injection either or opioid receptor agonists, DAMGO or DPDPE, respectively, caused a significant bilateral reduction in IOP (P<0.05) which was more pronounced in the ipsilateral than in the contralateral eye. Pretreatment with naloxone prevented some, but not all IOP reductions. CONCLUSION: The ARC takes part in the negative regulation of IOP, an action that may involve opioid neurons.

[Recent advances in viscocanalostomy for primary open-angle glaucoma].

Viscocanalostomy is used as the surgical intervention for open angle glaucoma. It has advantage of creating gradual filtration through the thin trabeculo-descemet membrane to reduce markedly the postoperative complications. Lately, many surgeons modified VCO, like combined it with phacoemulsification, or use the implant. Many to lower IOP to a greater degree and enhance success rates. This article reviewed the history of VCO, specially on the point of the surgical methods, effect, development, progress and tendency of VCO.

A retrospective and consecutive study of viscocanalostomy versus trabeculectomy for primary congenital glaucoma.

BACKGROUND: Surgical interventions are the main treatment for primary congenital glaucoma (PCG). This study aimed to compare the efficacy and safety between viscocanalostomy and mitomycin C (MMC)-trabeculectomy in patients with PCG. METHODS: A total number of 43 patients with PCG who underwent either viscocanalostomy (group 1) or MMC- trabeculectomy (group 2) between June 2003 and June 2008 were retrospectively reviewed. The patients' intraocular pressures (IOPs) were examined before surgery and on day 1, week 1, month 1, month 6, and month 12 post-operative. Mean horizontal corneal diameters, success rates, intra- and post-operative complications were compared between the two groups. RESULTS: Pre-operative IOPs were (31.96 ± 3.90) mmHg in group 1 and (32.56 ± 4.00) mmHg in group 2. At the last visit, IOPs were (16.78 ± 2.20) mmHg and (15.77 ± 2.60) mmHg, respectively (P < 0.001); the complete success rates of group 1 and group 2 were 45.9% and 67.4%, respectively, and the difference was not statistically significant (P = 0.158). There were no major complications occurred in the two groups. CONCLUSIONS: Both viscocanalostomy and trabeculectomy can lower IOP in PCG patients effectively. Although there was no major complications occurred in both groups, viscocanlostomy may decrease the probability of postoperative haemorrhage, hypotony, cataract, or choroid effusion.

[The effect of AQP4 knock out on retinal electrophysiology in laser-induced ocular hypertension mice].

OBJECTIVE: To investigate the effect of aquaporin 4 (AQP4) knock out (KO) on the dysfunction of retinal ganglion cells (RGC) in laser-induced ocular hypertension (OHT) mice. METHODS: Experimental study. AQP4 KO mice (n = 18, 36 eyes) and wide type (WT) mice (n = 18, 36 eyes) were used. Unilateral OHT was induced by laser photocoagulation in KO and WT mice after anesthesia. A simultaneous recording of PERG was performed by homemade electrodes. Intraocular pressure (IOP) was measured with an IcareLAB rebound tonometer every day at noon before and after surgery. The data was analysed by ANOVA and t test. RESULTS: In AQP4 KO mice, the mean P50 and P95 amplitudes were significantly (P < 0.01) reduced compared with WT mice [P50: KO: (5.53 ± 1.31) vs WT: (8.14 ± 1.24) µv t = 5.70 and P95: KO: (7.71 ± 1.89) vs WT: (11.30 ± 2.61) µv, t = 3.83, respectively]. The latencies of AQP4 KO mice in both P50 and N95 were shorter than those of WT (t = 5.70 and t = 3.83 respectively, P < 0.01). The mean IOP was significantly (P < 0.05) increased after photocoagulation in AQP4 KO and WT mice compared with pre-photocoagulation [KO post: (14.78 ± 1.80) mm Hg(1 mm Hg = 0.133 kPa) vs KO pre-photocoagulation: (6.61 ± 0.90) mm Hg and WT post: (16.44 ± 1.46) mm Hg vs WT pre-photocoagulation: (7.31 ± 0.98) mm Hg, respectively] with animals under general anesthesia. IOP was lowered mildly but significantly in KO mice when compare with WT mice (t = 3.09, P < 0.05) lasting seven days. IOP was gradually decreased to baseline values at day eight in both of KO and WT mice. CONCLUSIONS: Our results indicate that AQP4 null may damage retinal function that can be detected by the measurement of PEGR, a sensitive parameter to reflect the function of RGC.

Short-term efficacy of da Vinci robotic surgical system on rectal cancer in 101 patients / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the feasibility and safety of da Vinci robotic surgical system in rectal cancer radical operation, and to summarize its short-term efficacy and clinical experience.</p><p><b>METHODS</b>Data of 101 cases undergoing da Vinci robotic surgical system for rectal cancer radical operation from March 2010 to September 2012 were retrospectively analyzed. Evaluation was focused on operative procedure, complication, recovery and pathology.</p><p><b>RESULTS</b>All the 101 cases underwent operation successfully and safely without conversion to open procedure. Rectal cancer radical operation with da Vinci robotic surgical system included 73 low anterior resections and 28 abdominoperineal resections. The average operative time was (210.3±47.2) min. The average blood lose was (60.5±28.7) ml without transfusion. Lymphadenectomy harvest was 17.3±5.4. Passage of first flatus was (2.7±0.7) d. Distal margin was (5.3±2.3) cm without residual cancer cells. The complication rate was 6.9%, including anastomotic leakage(n=2), perineum incision infection(n=2), pulmonary infection (n=2), urinary retention (n=1). There was no postoperative death. The mean follow-up time was(12.9±8.0) months. No local recurrence was found except 2 cases with distant metastasis.</p><p><b>CONCLUSION</b>Application of da Vinci robotic surgical system in rectal cancer radical operation is safe and patients recover quickly The short-term efficacy is satisfactory.</p>

[Glaucoma clinical trials in China].

Large scale, multicenter, and randomized controlled glaucoma clinical trials are very important clinical research. The results of scientific evidences are useful to make clinical guideline of glaucoma prevention and management or working mode. Glaucoma is the second leading cause of blindness in the world, which is associated with irreversible damage to optic disc. At present, glaucoma prevalence in China was approximately 1.95% to 3.60%. In order to effectively prevent and treat glaucoma, it's necessary to promote and design glaucoma clinical trials that fit in our national medical care system. Much experience of carrying out clinical glaucoma trials has been obtained and achieved in the past. However, there is still a big gap between China and developed countries in such aspects as funding deficiency, disunity of operational standardization, quality irregularity and so on. This article presents a synthesis of modern principle data concerning glaucoma clinical trials in domestics and abroad aiming at emphasizing the importance of this issue.

[The effect of AQP4 gene on the activation of retinal glial cells in chronic high intraocular pressure mice].

OBJECTIVES: To investigate whether aquaporin 4 (AQP4) gene can affect the activation of glial cells and cause the injury of retina of chronic high intraocular pressure mice models, and to discuss its possible mechanism. METHODS: Experimental study. The chronic high intraocular pressure models were established by burning the scleral venous of the right eye, which as the experiment group, and the left eye without any treatment as the control group. The intraocular pressure (IOP) was measured by rebound tonometer. Selected each of the successful model of chronic high intraocular pressure male AQP4 knockout mice (AQP-/-) and their wild-type (WT) male mice 40, divided the two type of mice into five groups after scleral venous burn according to the time of establishing models (24 h, 3 d, 1 w, 2 w, 4 w after scleral venous burn), 8 mouse in each group. And then producing the paraffin sections of mouse eye. Immunohistochemical staining methods was used to observe the expression of the glial fibrillary acid protein (GFAP) in retina glial cells, and observe the expression of the AQP4 in the retina of the WT mouse. Image was acquired under the fluorescence microscopy. The intraocular pressure was analyzed by t-test. RESULTS: After scleral venous burn (24 h, 3 d, 1 w, 2 w, 4 w), there were significant difference (t = 6.66 - 18.08, all P value < 0.05) in the IOP of the AQP4-/- mice (11.30 ± 1.59, 11.20 ± 1.15, 10.60 ± 1.53, 10.75 ± 1.45, 10.45 ± 1.39) and WT mice (11.50 ± 2.56, 11.25 ± 1.65, 10.75 ± 1.33, 10.60 ± 1.33, 10.40 ± 1.19) between the experimental groups and control groups (6.60 ± 0.94, 6.35 ± 0.99, 6.55 ± 0.94, 6.45 ± 0.99, 6.50 ± 0.94 and 6.60 ± 1.05, 6.50 ± 0.89, 6.40 ± 1.09, 6.30 ± 1.13, 6.50 ± 1.05). Since 24 hours after the scleral venous burn, the expression of GAFP of the two type mice began to increase and reached to peak at 1 week after burning. This peak of WT mice was more obvious than that of AQP4-/- mice. The concentration of GAFP began to decrease at 2 weeks after burning and reached to bottom at 4 weeks later. To the WT mice, the expression of AQP4 was remarkable higher in experimental group than that in control group at 1 week after the scleral venous burn. The expression of AQP4 was related to the expression of GAFP in high intraocular pressure of WT mice at 1 w, 2 w, and 4 w after the scleral venous burn. CONCLUSIONS: The chronic high intraocular pressure models can be established successfully by burning the scleral venous. AQP4 gene can affect the activation of the glial cells in chronic high intraocular pressure mice and lead to the injury of retina.

[Comparative research of the efficacy of the gatifloxacin and levofloxacin for bacterial conjunctivitis in human eyes].

OBJECTIVE: To evaluate the different efficacy and safety to the treatment of bacterial conjunctivitis between the fluoroquinolone antibiotics gatifloxacin and levofloxacin. METHODS: A multi-centre, random, double-blind and control trial was performed in six centers including Eye Ear Nose and Throat Hospital of Fudan University, Henan Eye Institute, Eye Hospital Affiliated to Wenzhou Medical College, the First Affiliated Hospital Of Nanjing Medical University, Xijing Hospital Affiliated to the Fourth Military Medical University, the Second Affiliated Hospital of Xi'an Jiaotong University between August 2006 and October 2007. The levofloxacin was set as the efficient control. Two hundred and thirty-five patients (235 eyes) that diagnosed as bacterial conjunctivitis were randomly divided into two groups by the method of randomized blocks, the test group (gatifloxacin) had 118 eyes and the control (levofloxacin) group had 117 eyes. The drug delivery into conjunctival sac was performed at a 7-day period (two drops per time, eight times per day at the first two days and two drops per time, four times per day at the following 5 days). All participants were given the conjunctival sac germ culture and drug sensitive test before and after the study. The combination score of signs and symptoms and evaluation of safety were conducted at the pre-delivery day, the (4 ± 1) and (7 ± 1) delivery day. The statistic analysis was conducted by CMH χ(2) test, Pearson χ(2) test and Fisher's exact probabilities test. RESULTS: The efficacy of the two groups was 94.0% (110/117 eyes) in gatifloxacin group and 93.8% (106/113 eyes) in levofloxacin group with no significant difference (χ(2) = 0.052, P = 0.8201). There was also no difference in the bacteria clearance between the two groups [gatifloxacin versus levofloxacin, 94.1% (80/85 eyes) versus 92.5% (74/80 eyes), P = 0.3470]. The decrease of combination score of signs and symptoms at the (4 ± 1) delivery day was 4.436 ± 2.310 in the gatifloxacin group and 3.814 ± 1.962 in the levofloxacin group, the difference of which was significant (F = 7.280, P = 0.0075). This trend was also proved at the (7 ± 1) delivery day (gatifloxacin versus levofloxacin, 7.487 ± 2.821 versus 6.912 ± 2.911, F = 4.060, P = 0.0452). The visual acuity and the tolerance after local application of the eye drops between the two groups had no difference (the visual acuity F = 1.04, P = 0.3080; the tolerance after local admission χ(2) = 0.1372, P = 0.7111). According to the result of the germ culture, the major pathogenic bacteria were Gram-positive bacteria (totally 20 kinds of Gram-positive bacteria and 8 kinds of Gram-negative bacteria). The MIC and drug resistance of gatifloxacin to the Gram-positive bacteria was lower than that of the levofloxacin (Staphylococcus Epidermidis, Staphylococcus Aureus, coagulase negative Staphylococcus, α-hemolytic Streptococcus). CONCLUSIONS: The gatifloxacin eye drop has a good therapeutic effect to the bacterial conjunctivitis. It can effectively clear the pathogen with fast and strong effect. Moreover, it has a low MIC in vitro, advance a prospect in drug resistance, safety and ocular tolerance.

[Modified viscocanalostomy for the surgical treatment with primary open angle glaucoma].

OBJECTIVE: To compare the clinical outcome of trabeculectomy with viscocanalostomy in patients with primary open angle glaucoma (POAG). METHODS: 100 patients (100 eyes) with uncontrolled POAG were randomly assigned to either trabeculectomy group (50 eyes) or viscocanalostomy (VCO) group (50 eyes) and followed up for average 28 months. Intraocular pressure (IOP) was measured with a non-contact Topcon CT80 tonometer. RESULTS: At 1 month after operation, IOP was (11.22 +/- 4.34) and (12.35 +/- 3.79) mmHg (1 mmHg = 0.133 kPa, n = 50) in the eyes undergoing VCO or trabeculectomy surgery, respectively. The complete success rate (IOP < 21 mmHg without antiglaucoma medications) was 98.0% in both groups. There was no significant difference in IOP and complete success rate between both groups. At 12 months, IOP in VCO group was significantly (P < 0.05) lower (14.50 +/- 3.22) than that in trabeculectomy group (16.58 +/- 4.73) mmHg, while the complete success rate in VCO group (87.5%) was significantly higher (P < 0.05) than that in trabeculectomy group (70.0%). The early transient complications such as shallow anterior chamber and encysted blebs were significantly (P < 0.01) more common in trabeculectomy group than in VCO group. CONCLUSIONS: VCO appears to have long term advantages over trabeculectomy in terms of complete success rate, IOP control, and less early transient postoperative complications in POAG.

Genistein inhibited retinal neovascularization and expression of vascular endothelial growth factor and hypoxia inducible factor 1alpha in a mouse model of oxygen-induced retinopathy.

The effects of genistein on neovascularization, vascular endothelial growth factor (VEGF), and hypoxia inducible factor 1alpha (HIF1alpha) protein expression in a mouse model of oxygen-induced retinopathy were studied. The model of oxygen-induced retinal neovascularization was induced in newborn C57BL/6 mice by exposing 7-day-old mice to 75% oxygen for 5 days and then housing them in room air (relative hypoxia). Retinopathy was assessed by quantitation of vascular cell nuclei anterior to inner limiting membrane. Judged by relative fluorescence using a confocal scanning laser microscope coupled to a computer, VEGF and HIF1alpha protein expression were investigated. Genistein markedly inhibited the numbers of nuclei protruding above the inner limiting membrane under relative hypoxia conditions. The levels of nuclei numbers were suppressed by 50, 100, and 200 mg/kg body weight /day genistein to 87.4%, 72.0%, and 59.4%, respectively, compared to that untreated with genistein. VEGF protein was constitutively expressed in the preretinal area under normoxia conditions. Genistein markedly inhibited relative-hypoxia-elicited VEGF expression elevation in a dose-dependent manner. HIF1alpha expression was also observed in normoxia conditions. There was a 2.4-fold induction in preretinal HIF1alpha expression in oxygen-reared animals when compared to room-air-reared animals. Genistein dose-dependently suppressed HIF1alpha protein expression. These results indicated that the inhibition of VEGF and HIF1alpha protein expression by genistein may partly account for its effect on retinal neovascularization in vivo, and genistein could be an effective agent in the prevention and treatment of ocular neovascularization.

Genistein suppressed upregulation of vascular endothelial growth factor expression by cobalt chloride and hypoxia in rabbit retinal pigment epithelium cells.

The time course changes of vascular endothelial growth factor (VEGF) protein expression induced by cobalt chloride (CoCl(2)) and hypoxia and the effects of genistein on CoCl(2)- and hypoxia-induced VEGF expression in rabbit retinal pigment epithelium (RPE) cells were studied. Judged by relative fluorescence using a confocal scanning laser microscope coupled to a computer, VEGF protein expression exposed for different periods to CoCl(2) or hypoxia was investigated. CoCl(2) was found to significantly elevate VEGF protein expression. At 4 h after CoCl(2) treatment, the expression of VEGF protein was about three times as much as that at the start of treatment. Genistein (50, 100 and 200 microM) inhibited VEGF protein expression elicited by CoCl(2) in a concentration-dependent manner. Hypoxia (5% CO(2)/95% N(2)) could markedly increase VEGF protein expression. The elevation of VEGF protein expression was gradual and time-dependently. At 6 h, the highest expression of VEGF protein was observed, it was about three times as much as that at the start of treatment. After preincubation with 50, 100, and 200 microM genistein respectively, the hypoxia-evoked VEGF expression was concentration-dependently suppressed. These results indicated that genistein could be an effective agent in the prevention and treatment of intraretinal and subretinal neovascularization.