The ideal treatment timing for diabetic retinopathy: the molecular pathological mechanisms underlying early-stage diabetic retinopathy are a matter of concern.

Diabetic retinopathy (DR) is a prevalent complication of diabetes, significantly impacting patients' quality of life due to vision loss. No pharmacological therapies are currently approved for DR, excepted the drugs to treat diabetic macular edema such as the anti-VEGF agents or steroids administered by intraocular route. Advancements in research have highlighted the crucial role of early intervention in DR for halting or delaying disease progression. This holds immense significance in enhancing patients' quality of life and alleviating the societal burden associated with medical care costs. The non-proliferative stage represents the early phase of DR. In comparison to the proliferative stage, pathological changes primarily manifest as microangiomas and hemorrhages, while at the cellular level, there is a loss of pericytes, neuronal cell death, and disruption of components and functionality within the retinal neuronal vascular unit encompassing pericytes and neurons. Both neurodegenerative and microvascular abnormalities manifest in the early stages of DR. Therefore, our focus lies on the non-proliferative stage of DR and we have initially summarized the mechanisms involved in its development, including pathways such as polyols, that revolve around the pathological changes occurring during this early stage. We also integrate cutting-edge mechanisms, including leukocyte adhesion, neutrophil extracellular traps, multiple RNA regulation, microorganisms, cell death (ferroptosis and pyroptosis), and other related mechanisms. The current status of drug therapy for early-stage DR is also discussed to provide insights for the development of pharmaceutical interventions targeting the early treatment of DR.

The Synchronization Analysis of Cohen-Grossberg Stochastic Neural Networks with Inertial Terms.

The exponential synchronization (ES) of Cohen-Grossberg stochastic neural networks with inertial terms (CGSNNIs) is studied in this paper. It is investigated in two ways. The first way is using variable substitution to transform the system to another one and then based on the properties of i t ^ o integral, differential operator, and the second Lyapunov method to get a sufficient condition of ES. The second way is based on the second-order differential equation, the properties of calculus are used to get a sufficient condition of ES. At last, results of the theoretical derivation are verified by virtue of two numerical simulation examples.

The three syndromes and six Chinese patent medicine study during the recovery phase of COVID-19.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), first broke out in Wuhan, China, in 2019. SARS-CoV-2 develops many types of mutations (such as B.1.1.7), making diagnosis and treatment challenging. Although we now have a preliminary understanding of COVID-19, including pathological changes, clinical manifestations, and treatment measures, we also face new difficulties. The biggest problem is that most COVID-19 patients might face sequelae (e.g., fatigue, sleep disturbance, pulmonary fibrosis) during the recovery phase. We aimed to test six Chinese patent medicines to treat three major abnormal symptoms in COVID-19 patients during the recovery phase, including cardiopulmonary function, sleep disturbance, and digestive function. We launched the "three syndromes and six Chinese patent medicines" randomized, double-blind, placebo-controlled, multicenter clinical trial on April 10, 2020. The results showed that Jinshuibao tablets and Shengmaiyin oral liquid significantly improved the cardiopulmonary function of recovering COVID-19 patients. Shumian capsules, but not Xiaoyao capsules, significantly improved patients' sleep disorders. This might be because the indication of Xiaoyao capsules is liver qi stagnation rather than psychological or emotional problems. Xiangsha Liujun pills and Ludangshen oral liquid significantly improved digestive function. Our research provides a guideline for treating COVID-19 sequelae in patients during the recovery period based on high-quality evidence.

Identification and characterization of N9-methyltransferase involved in converting caffeine into non-stimulatory theacrine in tea.

Caffeine is a major component of xanthine alkaloids and commonly consumed in many popular beverages. Due to its occasional side effects, reduction of caffeine in a natural way is of great importance and economic significance. Recent studies reveal that caffeine can be converted into non-stimulatory theacrine in the rare tea plant Camellia assamica var. kucha (Kucha), which involves oxidation at the C8 and methylation at the N9 positions of caffeine. However, the underlying molecular mechanism remains unclear. Here, we identify the theacrine synthase CkTcS from Kucha, which possesses novel N9-methyltransferase activity using 1,3,7-trimethyluric acid but not caffeine as a substrate, confirming that C8 oxidation takes place prior to N9-methylation. The crystal structure of the CkTcS complex reveals the key residues that are required for the N9-methylation, providing insights into how caffeine N-methyltransferases in tea plants have evolved to catalyze regioselective N-methylation through fine tuning of their active sites. These results may guide the future development of decaffeinated drinks.

Sirt3-dependent deacetylation of COX-1 counteracts oxidative stress-induced cell apoptosis.

The mitochondrial complexes are prone to sirtuin (Sirt)3-mediated deacetylation modification, which may determine cellular response to stimuli, such as oxidative stress. In this study, we show that the cytochrome c oxidase (COX)-1, a core catalytic subunit of mitochondrial complex IV, was acetylated and deactivated both in 2,2'-azobis(2-amidinopropane) dihydrochloride-treated NIH/3T3 cells and hydrogen peroxide-treated primary neuronal cells, correlating with apoptotic cell death induction by oxidative stress. Inhibition of Sirt3 by small interfering RNA or the inhibitor nicotinamide induced accumulation of acetylation of COX-1, reduced mitochondrial membrane potential, and increased cell apoptosis. In contrast, overexpression of Sirt3 enhanced deacetylation of COX-1 and inhibited oxidative stress-induced apoptotic cell death. Significantly, rats treated with ischemia/reperfusion injury, a typical oxidative stress-related disease, presented an inhibition of Sirt3-induced hyperacetylation of COX-1 in the brain tissues. Furthermore, K13, K264, K319, and K481 were identified as the acetylation sits of COX-1 in response to oxidative stress. In conclusion, COX-1 was discovered as a new deacetylation target of Sirt3, indicating that the Sirt3/COX-1 axis is a promising therapy target of stress-related diseases.-Tu, L.-F., Cao, L.-F., Zhang, Y.-H., Guo, Y.-L., Zhou, Y.-F., Lu, W.-Q., Zhang, T.-Z., Zhang, T., Zhang, G.-X., Kurihara, H., Li, Y.-F., He, R.-R. Sirt3-dependent deacetylation of COX-1 counteracts oxidative stress-induced cell apoptosis.

Effects of thermal treatment on the properties of defatted soya bean flour and its adhesion to plywood.

With an attempt to economically and efficiently improve the water resistance of defatted soya bean flour (DSF)-based wood adhesives, DSF was subjected to thermal treatment at various temperatures (65°C, 80°C, 95°C, 110°C and 125°C) for 30 min. The effects of thermal treatment temperature onto the chemical structure, crystalline degree, water-insoluble content and acetaldehyde value of the thermally treated DSF (T-DSF) were investigated. The thermal stabilities and bonding properties of soya bean adhesives prepared from T-DSF and cross-linker epichlorohydrin-modified polyamide (EMPA) were also investigated. Test results indicated that both the water-insoluble content and the acetaldehyde value of T-DSF increased after thermal treatment, reaching the highest values of 27.28% and 26.81 mg g-1, respectively. All plywood bonded with the T-DSF-based adhesive withstood a 28 h boiling-dry-boiling accelerated ageing treatment, while plywood bonded with the DSF-based adhesive delaminated after 4 h of water boiling, demonstrating the significantly improved water resistance of the T-DSF-based adhesives. Related analyses also confirmed that this improvement was due to: (i) the formation of insoluble cross-linked structures of T-DSF resulting from protein-protein self-cross-linking reactions and the protein-carbohydrate Maillard reaction and (ii) increased cross-linking efficiency between T-DSF and cross-linker EMPA owing to more T-DSF-reactive groups being released after thermal treatment.

Mitochondrial expression and activity of P-glycoprotein under oxidative stress in outer blood-retinal barrier.

AIM: To investigate the role of oxidative stress in regulating the functional expression of P-glycoprotein (P-gp) in mitochondria of D407 cells. METHODS: D407 cells were exposed to different ranges of concentrations of H2O2. The mitochondrial location of P-gp in the cells subjected to oxidative stress was detected by confocal analysis. Expression of P-gp in isolated mitochondria was assessed by Western blot. The pump activity of P-gp was evaluated by performing the efflux study on isolated mitochondria with Rhodamine 123 (Rho-123) alone and in the presence of P-gp inhibitor (Tariquidar) using flow cytometry analysis. The cells were pretreated with 10 mmol/L N-acetylcysteine (NAC) for 30min before exposing to H2O2, and analyzed the mitochondrial extracts by Western blot and flow cytometry. RESULTS: P-gp was co-localized in the mitochondria by confocal laser scanning microscopy, and it was also detected in the mitochondria of D407 cells using Western blot. Exposure to increasing concentrations of H2O2 led to gradually increased expression and location of P-gp in the mitochondria of cells. Rho-123 efflux assay showed higher uptake of Rho-123 on isolated mitochondria in the presence of Tariquidar both in normal and oxidative stress state. H2O2 up-regulated P-gp in D407 cells, which could be reversed by NAC treatment. CONCLUSION: H2O2 could up-regulate the functional expression of P-gp in mitochondria of D407 cells, while antioxidants might suppress oxidative-stress-induced over-expression of functional P-gp. It is indicative that limiting the mitochondrial P-gp transport in retinal pigment epithelium cells would be to improve the effect of mitochondria-targeted antioxidant therapy in age-related macular degeneration-like retinopathy.

HSVtk/GCV system on hepatoma carcinoma cells: Construction of the plasmid pcDNA3.1­pAFP-TK and targeted killing effect.

Previous studies demonstrated that herpes simplex virus thymidine kinase (HSVtk) could phosphorylate non­toxic gancyclovir (GCV) efficiently to produce phosphorylated products that result in cell apoptosis, to kill tumor cells. The present study aimed to construct a plasmid vector, pcDNA3.1­pAFP­TK, carrying the suicide gene driven by the alpha­fetoprotein (AFP) promoter, to investigate the cytotoxicity of HSVtk/GCV suicide gene system on hepatoma carcinoma cells. Reverse transcription­polymerase chain reaction and western blotting results demonstrated that the HSVtk gene was effectively expressed in HepG2 hepatoma carcinoma cells transfected with pcDNA3.1­pAFP­TK plasmid, whereas HSVtk gene expression was not detected in normal HL­7702 liver cells. In addition, MTT assays indicated that cell viability of HepG2 cells with the plasmid pcDNA3.1­pAFP­TK decreased in a dose­dependent manner following treatment with GCV for 48 h. Flow cytometry also revealed that the cell apoptosis rate and mitochondrial membrane potential reduction rate in the HepG2 cells treated with HSVtk/GCV suicide gene system were significantly higher than in the control group. Apoptosis rates in the control group and the pcDNA3.1­pAFP­TK group were (1.00±0.62%) and (38.70±6.03%), respectively. Mitochondrial membrane potential reduction rates in the control group and the pcDNA3.1-pAFP-TK group were (0.57±0.11%) and (22.84±5.79%), respectively. Caspase­3 staining demonstrated that activated caspase­3 increased significantly in the HepG2 cells treated with HSVtk/GCV suicide gene system, whereas in the control group activated caspase­3 increase was not observed. The results of the present study, therefore, indicated that HSVtk suicide gene was obviously expressed in the HepG2 cells and that the HSVtk/GCV system was effective at killing HepG2 hepatoma carcinoma cells.

TMPyP4-regulated cell proliferation and apoptosis through the Wnt/ß-catenin signaling pathway in SW480 cells.

BACKGROUND: The aim of this study was to investigate the potential effects of the 5, 10, 15, 20-tetrakis (1-methylpyridinium-4-yl) porphyrin (TMPyP4) on the proliferation and apoptosis of SW480 cells and the underlying mechanisms by which TMPyP4 exerted its actions. METHODS: After treated with different doses of TMPyP4, cell viability was determined by MTT method, the apoptosis was observed by flow cytometry (FCM) and the expression of Wnt, GSK-3ß, ß-catenin and cyclinD1 was measured by RT-PCR and Western blot analysis. RESULTS: The analysis revealed that TMPyP4 potently suppressed cell viability and induced the apoptosis of SW480 cells in a dose-dependent manner. In addition, the downregulation of Wnt, ß-catenin and cyclinD1 expression levels was detected in TMPyP4-treated SW480 cells. However, followed by the block of Wnt signaling pathway using siRNA methods, the effects of TMPyP4 on proliferation and apoptosis of SW480 cells were significantly reduced. CONCLUSION: It indicates that the TMPyP4-inhibited proliferation and -induced apoptosis in SW480 cells was accompanied by the suppression of Wnt/ß-catenin signaling pathway. Therefore, TMPyP4 may represent a potential therapeutic method for the treatment of colon carcinoma.

Anticipation, anti-glaucoma drug treatment response and phenotype of a Chinese family with glaucoma caused by the Pro370Leu myocilin mutation.

AIM: To describe the anticipation and anti-glaucoma drugs response of a Chinese family with juvenile-onset open angle glaucoma (JOAG) caused by the Pro370Leu myocilin (MYOC) mutation. METHODS: Fifteen members of a three-generation Chinese family with JOAG were recruited to this study. They all underwent ophthalmic common examinations. Patients suspected to have JOAG got an assessment of visual field and optical coherence tomography. Intraocular pressures (IOPs) of four patients were measured at 8, 10, 12, 14, 17 o'clock respectively after using anti-glaucoma drugs. Mutation screening of all MYOC gene coding exons of the participants was performed by using direct sequencing of PCR products. RESULTS: Clinical examinations and pedigree analysis revealed eight family members were suffered from JOAG. Apparent genetics anticipation phenomenon was observed in this family. Their clinical features included elevated IOP of 35-55mmHg, loss of visual field, thinning of retinal nerve fiber layer, and glaucomatous optic disc damage. Noticeably, their intraocular pressure levels could be controlled within normal range at 8 and 10 o'clock by anti-glaucoma drugs, but their IOPs would elevate >21mmHg after 12 o'clock. Seven patients received trabeculectomy produced thin-walled, pale, and saccate filtering blebs maintaining lower intraocular pressure efficiently. Mutation screening indentified a heterozygous C→T missense mutation in the MYOC gene at position 1 109 in exon 3, corresponding to a substitution of a highly conserved proline to leucine at codon 370 in the olfactomedin domain of MYOC. CONCLUSION: The clinical characteristics of JOAG in this family were 1) genetics anticipation; 2) high IOP; 3) temporay response to anti-glaucoma drugs; 4) filtering surgery produced thin-walled and saccate filtering blebs, helping maintain lower IOP.

Detecting and (not) dealing with plagiarism in an engineering paper: beyond CrossCheck-a case study.

In papers in areas such as engineering and the physical sciences, figures, tables and formulae are the basic elements to communicate the authors' core ideas, workings and results. As a computational text-matching tool, CrossCheck cannot work on these non-textual elements to detect plagiarism. Consequently, when comparing engineering or physical sciences papers, CrossCheck may return a low similarity index even when plagiarism has in fact taken place. A case of demonstrated plagiarism involving engineering papers with a low similarity index is discussed, and editor's experiences and suggestions are given on how to tackle this problem. The case shows a lack of understanding of plagiarism by some authors or editors, and illustrates the difficulty of getting some editors and publishers to take appropriate action. Consequently, authors, journal editors, and reviewers, as well as research institutions all are duty-bound not only to recognize the differences between ethical and unethical behavior in order to protect a healthy research environment, and also to maintain consistent ethical publishing standards.

Inhibitory effect of curcumin on the Al(III)-induced Aß42 aggregation and neurotoxicity in vitro.

The pathogenesis of Alzheimer's disease (AD) involves a key event which changes the morphology of amyloid-ß 42 (Aß)42 peptide from its soluble monomeric form into the fibrillated aggregates in the brain. Aluminum ion, Al(III), is known to act as a pathological chaperone of the Aß42 in this process; curcumin, a natural phenolic compound, is considered capable of binding Al(III) and Aß42; nevertheless, little is known about the combined action of curcumin and Al(III) on the Aß42 fibrillation and neurotoxicity. Here, combinations of circular dichroism spectroscopy, thioflavin T fluorescence, atomic force microscopy, Bradford and MTT assays, it is demonstrated that although Al(III) can promote the Aß42 fibrillation dose-dependently, leading to the high neurotoxicity to PC12 cells, curcumin can inhibit the events. Besides, we found that curcumin is able not only to inhibit the formation of Al(III)-induced Aß42 fibrillation, but also to form the Al(III)-curcumin complexes which in turn can remold the preformed, mature, ordered Aß42 fibrils into the low toxic amorphous aggregates. These findings suggest that curcumin could block the binding of Al(III) with Aß42 and form the Al(III)-curcumin complexes, so as to inhibit the Al(III)-induced Aß42 fibrillation and neurotoxicity. The Al(III)-curcumin complexes are worth potentially developing as a therapy agent against the neurodegenerative disorders in the future.

[Effects of morphine and pethidine on the expression of P-glycoprotein in mouse brain microvascular endothelial cells].

OBJECTIVE: To observe the effects of morphine and pethidine on P-glycoprotein (P-gp) expression in mouse brain microvascular endothelial cells and investigate the role of nuclear factor-kappaB (NF-kappaB) signaling pathway in morphine-induced up-expression of P-gp. METHODS: The mouse brain microvascular endothelial cell line (b.END3) was subjected to pre-incubation with NF-kappaB inhibitor PDTC (5 micromol/L) for 1 h followed by stimulation with morphine (1 microg/ml) or pethidine (1 microg/ml) for 24 h. The bEnd.3 cells were then collected for Western blotting for P-gp expression. RESULTS: A 24-h morphine stimulation induced an up-expression of P-gp in bEnd.3 cells by almost 200%. Pethidine in similar conditions did not affect P-gp expression in the cells. PDTC, the specific inhibitor of NF-kappaB, inhibited morphine-induced up-expression of P-gp in the cells. CONCLUSION: Morphine can induce up-expression of endogenous P-gp in mouse brain microvascular endothelial cells. NF-kappaB signaling pathway is involved in the morphine-induced up-expression of P-gp.

Hepatocyte gene transfer mediated by stable polyplexes based on MPP-containing DNA complexes.

BACKGROUND: In the field of gene therapy, viral vectors as delivery tools have a number of disadvantages for medical application. This study aimed to explore a novel nonviral vector as a vehicle for gene therapy. METHODS: Transvector-rpE-MPP and EGFP (enhanced green fluorescent protein) were used as the gene transfer carrier and the reporter gene, respectively. Polyplexes which integrate transvector-rpE-MPP, the object gene, and EGFP were formed. The optimal charge ratio, stability, and transduction capacity of the polyplexes in mouse hepatocytes in vitro and in mouse liver in vivo were investigated. The polyplexes of transvector-rpE-MPP and pcDNA(3)-EGFP, with charge ratios of 0, 0.25, 0.5, 0.75, 1 and 1.5 were compared to determine the optimal charge ratio. RESULTS: Polyplexes with charge ratios of 1:1 were most stable; pcDNA(3)-EGFP in these complexes resisted digestion by DNase I and blood plasma. On the other hand, pcDNA(3)-EGFP alone was digested. Fluorescence analysis indicated that transvector-rpE-MPP successfully delivered the reporter gene EGFP into hepatocytes and that EGFP expression was detected in hepatocyte cultures and in liver tissue. CONCLUSION: These results have laid a foundation for further study of a novel nonviral gene delivery system.

[Medium- and long-chain fatty acid triacylglycerol reduce body fat and serum triglyceride in overweight and hypertriglyceridemic subjects].

OBJECTIVE: To investigate effects of medium- and long-chain fatty acid triacylglycerols (MLCT) on body fat and serum lipid in overweight and hypertriglyceridemic subjects. METHODS: A double-blind, controlled clinical trial was carried out, in which 112 subjects with hypertriglyceridemia were enrolled and divided into two groups, there were 56 subjects in each group. One group was randomized to consume long-chain fatty acid triacylglycerol (LCT), and the other to MLCT. All volunteers were asked to consume 25 - 30 g test oil daily for consecutive 8 weeks. Anthropometric measurements of body weight, body fat weight, waist circumference(WC), hip circumference(HC), WHR (ratio of WC/HC), total fat weight, subcutaneous fat area, visceral fat area, and serum biochemical variables of glucose, total cholesterols(TC), triglycerides(TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C)were measured at the initial and final time of the study. RESULTS: 11 subjects were excluded from the study because of various reasons. Of the 101 included cases, there were 50 (male subject 34, 68.0%) and 51 (male subject 33, 64.7%) subjects left in LCT and MLCT group respectively. The proportion of men in MLCT (64.7%, 33/51) was not significantly different (chi(2) = 0.1227, P > 0.05) compared to those in LCT (68.0%, 34/50). The average age of MLCT was (54.2 +/- 12.5) which was not significantly different (t = 0.39, P > 0.05) compared to those in LCT (53.2 +/- 13.0); Body mass index (BMI) of MLCT was (25.9 +/- 3.3) kg/m(2), which was not significantly different (t = 0.08, P > 0.05) compared to those of LCT (25.9 +/- 2.4) kg/m(2). After consumption of test oil for 8 weeks, extent of decrease in BMI, percent of body fat, subcutaneous fat, serum TG and serum LDL-C in overweight subjects of MLCT were (-0.73 +/- 0.61) kg/m(2), (-1.53 +/- 1.32)%, (-16.29 +/- 19.25) cm(2), (-0.57 +/- 0.86) mmol/L and (-0.05 +/- 0.64) mmol/L respectively, those in overweight subjects of LCT were (-0.19 +/- 0.61) kg/m(2), (-0.58 +/- 1.02)%, (4.69 +/- 19.06) cm(2), (0.65 +/- 1.10) mmol/L and (0.38 +/- 0.58) mmol/L respectively, all of them were significantly different (the value of t were -2.70, -2.43, -3.20, -3.81 and -2.09 respectively, all of P value were less than 0.05). CONCLUSION: Consumption of MLCT can reduce body fat weight and serum triacylglycerol and LDL-C in overweight hypertriglyceridemic subjects under an appropriate dietary regime.

Mitochondrial complex I defect induces ROS release and degeneration in trabecular meshwork cells of POAG patients: protection by antioxidants.

PURPOSE: There is growing evidence that oxidative stress contributes to the progression of primary open-angle glaucoma (POAG), a leading cause of irreversible blindness worldwide. The authors provide evidence that mitochondrial dysfunction is a possible mechanism for the loss of trabecular meshwork (TM) cells in persons with POAG. METHODS: TM from patients with POAG (GTM) and age-matched subjects without disease (NTM) were obtained by standard surgical trabeculectomy. Primary TM cultures were treated with one of the following mitochondrial respiratory chain inhibitors: rotenone (ROT, complex I inhibitor), thenoyltrifluoroacetone (TTFA, complex II inhibitor), myxothiazol or antimycin A (MYX, AM-complex III inhibitors); mitochondrial permeability transition (MPT) inhibitor cyclosporine A (CsA); and antioxidants vitamin E (Vit E) or N-acetylcysteine (NAC). Mitochondrial function was determined by changes in mitochondrial membrane potential (DeltaPsim) and adenosine triphosphate (ATP) production with the fluorescent probes 5,5',6,6'-tetrachloro-1,1'3,3'-tetraethylbenzimid azolocarbocyanine iodide (JC-1) and a luciferin/luciferase-based ATP assay, respectively. Reactive oxygen species (ROS) level, determined by H(2)-DCF-DA, and cell death, measured by lactate dehydrogenase activity and Annexin V-FITC labeling, were also examined. RESULTS: GTM cells have higher endogenous ROS levels, lower ATP levels, and decreased Delta Psi m and they are more sensitive to mitochondrial complex I inhibition than their normal counterparts. ROT induces a further increase in ROS production, the release of cytochrome c, and decreases in ATP level and Delta Psi m in GTM cells, eventually leading to apoptosis. Complex II and III inhibition had little effect on the cells. Antioxidants protect against ROT-induced death by inhibiting ROS generation and cytochrome c release. CONCLUSIONS: The authors propose that a mitochondrial complex I defect is associated with the degeneration of TM cells in patients with POAG, and antioxidants and MPT inhibitors can reduce the progression of this condition.

[The protective effect of hypoxic preconditioning against light-induced photoreceptor degeneration in mice].

OBJECTIVE: To study the protective roles of hypoxic preconditioning in light induced retinal injury in a mice model and investigate the possible mechanism of related gene regulation. METHODS: 54 BALB/c mice were randomly divided into simple light exposure group (SL), hypoxic pretreatment group (HP) and control group (CON). The mice of SL and HP were continually exposed to light for 3 h, which built model of light-induced damage. Morphologic changes of photoreceptor cells in different group were examined by light microscope and the apoptosis was detected by TdT-mediated dUTP nick end labeling. Different expressions of c-fos and caspase-1 gene were examined by immunohistochemical staining. RESULTS: In group SL, the photic injury appeared very obviously and early. Different changes appeared in the outer nuclear layer after light exposure. Photic injury was aggravated following the increased light exposure. Positive staining of c-fos and caspase-1 could be seen in the outer nuclear layer. In group HP, the changes of retinal morphology appeared slightly and lately. Compared with group SL, caspsae-1 expression was decreased obviously, while no difference was seen in the expression of c-fos. The retinal structures was normal in the mice of control group and c-fos and caspase-1 were stained negative. CONCLUSION: Hypoxic preconditioning has neuroprotective effect on photoreceptor cells by inhibiting the expression of apoptosis-related genes in photic injured mice model. caspase-1 may be involved in the protective mechanism.

[Erythropoietin administration protects retina against light-induced retinal degeneration].

OBJECTIVE: To study whether recombinant human erythropoietin can pass through mice blood-retina barrier and the protective role in light-induced damage in retina. METHODS: After the injection of rHEPO, the content of rHEPO in 24 BALB/c mice retina was examined by enzyme linked immunosorbent assay (ELISA). 24 BALB/c mice were used to establish a light-induced damaged model, the difference of retina in rHEPO group and control group was compared using light microscope and TdT-mediated dUTP nick end labeling (TUNEL). RESULTS: The amount of retinal rHEPO in four deferent time points was (0.68 +/- 0.24) mU, (1.87 +/- 0.37) mU, (0.96 +/- 0.24) mU, (0.47 +/- 0.13) mU in 100 microg retinal total protein respectively by ELISA assay, there were statistical significances among groups. The density of rHEPO in the retina reached its peak at 4th hour after injection. Histology analysis: rHEPO group, at the 12th hour after light exposure the inner segment became condensed and disorganized. At the 36th hour the retina disorganized and vesiculated were seen in outer segments. At the 72nd hour the inner and outer segments were damaged more seriously and the outer nuclear layer became thinner and denser. On the 7th day, the retinal outer nuclear layer became thinner and condenses. rHEPO group showed a minimal damage in every time points but outer nuclear layer disorganized and vesiculated in inner and outer segments. No obvious changes in retinal thickness. The apoptotic cells were detected by TUNEL. At the 12th hour after light exposure, there were the apoptotic cells in outer nuclear layer near outer plexiform layer. At 36th hour the numbers of apoptotic cells were increased, however at the 72nd it was decreased obviously, only a few scattering apoptotic cells were revealed in the outer nuclear layer. Numbers of apoptotic cells between the rHEPO group and control group in outer nuclear layer were statistical significance (P < 0.01). CONCLUSIONS: rHEPO can pass through the mice blood-retina barrier and rHEPO has neuroprotective effect on mice retina. rHEPO may be used to treat degenerative retinal diseases.