Pyroptosis is a newly discovered form of cell death. Through the activation of inflammasome complexes, pyroptosis induces the production of interleukin (IL) -1β and IL-18, and the osmotic swelling of cells, thus induces cellular rupture and death. It plays a role in the pathological process of a variety of human diseases. The death of retinal cells including photoreceptor cells and retinal pigment epithelium (RPE) cells is the main reason leading to visual dysfunction in the pathogenesis in ocular fundus diseases. Researches have demonstrated that pyroptosis is closely related to the onset and progression of various retinal diseases. In age-related macular degeneration, pyroptosis directly causes apoptosis of RPE cells and upregulation of pro-inflammatory factors, enhancing toxic effect of lipofuscin. For retinitis pigmentosa, pyroptosis is the leading manner of death of secondary cone photoreceptor cells. In cytomegalovirus retinitis, pyroptosis is the main responding way to infection. This review presented the molecular mechanism of pyroptosis and its role in age-related macular degeneration, retinitis pigmentosa and cytomegalovirus retinitis and other retinal diseases.
Objective To determine the effects of lensspecific overexpression of OSM on the eye development. Methods A truncated mouse OSM c DNA (661 bp) was linked to the αA-crystallin promoter. Transgenic mice were characterized by routine histological and immunohistochemical techiniques. TUNEL assays were used to de tect cell death. The mRNA expression of caspase-3 was detected by in situhybridization, Rabbit anti-cleavage caspase-3 antibody was used to detectactive capase-3. Results At embryonic day (E) 14.5 and 17.5, expression of the OSM transgenic protein was detected specifically in lens fiber cells. The onset of retinal degeneration in the mid portion of the transgenic retinae was observed started from E17.5. By the time of birth 50% or more of the retinal cells were missing. The OSM transgenic retinal cells underwent apoptosis indicated by TUNEL assays. Most strikingly, activation of caspase-3 protein were observed throughout the transgenic retinas. Conclusions Lens-specific overexpression of OSM activate caspase-3, leading to abnormal eye development,apoptosis and widespread retinal degeneration. (Chin J Ocul Fundus Dis，2003，19：201-268)
Objctive To explore the relationship between the expression of Fas/FasL and the apoptosis occurs in retinal ischemia/reperfusion injury of rats , as well as the therapeutic effects of bFGF on the ischemic retina.Methods Th emodels of retinal ischemia/reperfusion injury was made by transient elevating introcular pressure. A total of 28 rats were divided into normal and operation group.The latter were subdivided into 1 hour, 6, 12, 24, 48 and 72 hours after reperfusion group, in which the left eyes of the rats were in the ischemia/reper fusion groups and the right ones were in the treatment groups (bFGF intracameral injection). Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL) method, and the expression of Fas and Fas ligand was studied by strept avidin-biotin complex （SABC）immunohistochemistry. Results No positive cells were observed in the normal rats′retinae, but there was a significant number of TUNEL positive cells in 6-24 hours after transient ischemia followed by a decrease at the 48th hour. The number of TUNEL positive cells reached a maximum at the 24th hour after ischemia. The expression of Fas gradually increased as early as when it was at the 6th hour, reached a peak at the 24th hour, and then decreased at the 48th hour. Similarly, the expression of Fas ligand was at peak in 24-48 hours in GCL and INL of retina. Conclusions Retinal ischemia-reperfusion after transient elevated IOP induced apoptosis of cells in the retina. Fas/FasL may play an important role in the early events of the apoptotic pathways. bFGF can rescue RGCs from retinal ischemia/reperfusion injury through downregulation of the expression of Fas/FasL and may represent an important mechanism for therapeutic neuroprotection. (Chin J Ocul Fundus Dis，2003，19：160-163)
Objective To observe apoptotic and proliferative characteristics of the retinal vascular end othelial cells (RVECs) of the 1～16 weeks diabetic rats and p53 and bcl-2 expressions of the rats,in order to probe the pathogenic mechanism of diabetic retinopathy(DR). Methods Models of diabetic Wistar rats were made by alloxan venous injection.The retinal blood vessels were filled by ink,the wholemounts and paraffin-embedded sections of the retinas were made,TUNEL staining and Immunohistochemical ABC staining were used,and light microscopy was taken,in succession. Results Apoptosis of the RVECs was not found.Compared with control group,the morphologic features of the RVECs and the structure of the retinal blood vessels remained unchanged.In the period from the 10th to the 16th week,the immunohistochemical stain of PCNA,BrdU,p53,and bcl-2 for RVECs revealed positive results,but there was no any sign of the RVECs stacking and proliferating or new blood vessels forming in the retinas.In control group,the reaction of immunological stain of the aforementioned parameters was negative. Conclusions No accelerated apoptosis and proliferation of the RVECs in the 1～16 week diabetic rats happen after alloxan injection.Almost all of the RVECs were stimulated to enter the cell cycle in the 10th week.Expression of p53 and bcl-2 might play an important role in stabilizing the RVECs in early stage of diabetes. (Chin J Ocul Fundus Dis, 1999, 15: 157-159)
Objective To observe the protective effects of Na2SeO3 on the damage of retinal neuron induced by microwave. Methods Cultured fluids of retinal neuron were divided into 4 groups,including 1 group of control, according to the concentration of Na2SeO3 in cultured fluid and then exposed to 30 mW/cm2 microwave for 1 hour.The targets of lipid peroxidation and the concentration of selenium in cells were measured.Apoptosis detection was taken by TUNEL detection kit. Results The activity of SOD and GSH-Px rised,meanwhile the content of MDA and the amount of apoptosis cells decreased in 1times;107 mol/L group compared with the group without Na2SeO3.The other groups was superior in antioxdant capacity to 1times;107 mol/L group. Conclusion Na2SeO3 might be possessed of the effect of protecting the damage of retinal neuron induced by microwave. (Chin J Ocul Fundus Dis,2000,16:97-99)
Objective To demonstrate if apoptosis is one of the mechanisms of siderotic retinopathy. Methods Autoclaved iron particles were implanted in the vitreous cavities of 32 eyes of SD rats.Glass chips were implanted in 10 control eyes.The experimental eyes were enucleated at various time intervals from days 1 to 15.Retinal degeneration was examined using the TdT-mediated,dUTP-biotin nickend labeling(TUNEL)method.Electrophoresis on agarose gel was used to detect internucleosomal DNA fragmentation.Results TUNEL-positive nuclei were observed only in the outer nuclear layer beginning on day 2.The nuclei spread throughout the outer nuclear layer by the end of day 3.No TUNEL-positive nuclei were observed in other layers throughout the experimental perios.Analysis of DNA,extracted from the retinas by electrophoresis on agarose gel,revealed a typical ladder pattern of internucleosoma DNA cleavage in the experimental eyes.ConclusionApoptosis of photoreceptors occurs at the early phase of iron-induced retinopathy in the rats.
Objective To investigate the damage to the retinal cells and apoptosis of retinal cells of rats after ischemia-reperfusion insult. Methods The retinal ischemia-reperfusion model was developed by increasing intraocular pressure to 109725 mm Hg in rat eyes. Morphological changes of the rat eyes were observed by means of routine histopathology with HE staining. Apoptosis of the retina was assayed by both DNA fragmentation gel-electrophoresis and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL). Results Compared with the normal control, no histopathological changes were revealed in the rat retinas 30 min after the ischemia and then reperfued for 24 h or 48 h. Retinal ganglion cell layer (RGL) and inner plaxiform layer (IPL) of the retina were observed, however, to become significantly thinner 60 min after the ischemia and then reperfued for 24 h or 48 h. Together with the pathological changes DNA ladder pattern was detected in the same group of the rats. Further, immunochemical stain of the eye demonstrated that TUNEL positive cells were localized in RGL and IPL of the retina. Conclusion Ischemia-reperfusion insult of the eye may remarkably damage the retina of the rat eye. The damage to the retinal cells is mainly localized within RGL and IPL and apoptosis is the important mechanism of the retinal disorder. (Chin J Ocul Fundus Dis, 2002, 18: 296-298)
ObjectiveTo explore the expression of programmed cell death 4 (PDCD4) in different subtype of breast cancer and its relationship to prognosis. MethodsThree hundred and thirty-eight patients with breast cancer from January 2007 to December 2009 in this hospital were collected. All these patients were categorized into three subtypes which was luminal, HER-2 positive, and triple negative according to the results of immunohistochemical stain. SP immunohistochemistry was used to detect the expression of PDCD4 in the different subtype of breast cancer. Kaplan-Meier and Cox proportional hazards model was used to analyze the prognosis. Results①The positive rate of PDCD4 expression was 73.37%(146/199), 30.16%(19/63), and 35.53%(27/76) in the luminal, HER-2 positive, and triple negative breast cancer, respectively. The expression of PDCD4 was downregulated especially in the HER-2 positive and triple negative breast cancer(χ2=38.315, P=0.000; χ2=33.746, P=0.000) as compared with the luminal breast cancer. 2 The disease free survival and overall survival rates in the PDCD4 positive patients were significantly higher than those in the PDCD4 negative patients(P < 0.05) despite the subtypes.③Cox model revealed that T staging, N staging, and PDCD4 were the independent prognostic factors for disease free survival and that histological grade, T staging, N staging, and PDCD4 were the independent prognostic factors for overall survival. ConclusionsPDCD4 expression is downregulated in all subtypes of breast cancer especially in HER-2 positive and triple negative breast cancer, and the loss of PDCD4 expression is correlated to poor prognosis. PDCD4 is an independent prognostic factor of breast cancer.