Regional anesthesia in a patient with primary ciliary dyskinesia:A case report

BACKGROUND Primary ciliary dyskinesia(PCD)is an inherited autosomal-recessive disorder of impaired mucociliary clearance characterized by chronic respiratory diseases,otolaryngological diseases,central nervous system abnormalities,reproductive system abnormalities,and cardiac function abnormalities.General anesthesia in these patients is associated with a higher incidence of respiratory complications than in patients without the disease.CASE SUMMARY A 16-year-old male patient was referred to the emergency room complaining of right ankle pain due to distal tibiofibular fracture.Three years prior,he had been diagnosed with PCD.At that time,he had experienced several episodes of pneumonia,sinusitis,and chronic middle ear infections,for which he underwent surgical interventions.At the current admission,he presented with cough and sputum but no other respiratory symptoms.A chest computed tomography scan revealed centrilobular ground-glass opacities in both lower lobes and a calcified nodule in the left lower lobe.For the surgical procedure and postoperative pain management,combined spinal-epidural anesthesia was employed.The patient’s postoperative pain score was measured by the numerical rating scale(NRS).On the day of surgery,his NRS was 5 points.By the second postoperative day,the NRS score had decreased to 2–3 points.The epidural catheter was removed on the fourth day following the operation.The patient was subsequently discharged no respiratory complications.CONCLUSION We performed combined spinal-epidural anesthesia in a patient with PCD.The patient experienced no additional respiratory complications and was discharged with a low NRS score for pain.

Electroacupuncture alleviates ciliary muscle cell apoptosis in lens-induced myopic guinea pigs through inhibiting the mitochondrial signaling pathway

AIM:To investigate the effect of electroacupuncture(EA)on the mitochondria-dependent apoptotic signaling pathway in the ciliary muscle of guinea pigs with negative lensinduced myopia(LIM).METHODS:Guinea pigs were randomly divided into normal control(NC)group,LIM group,LIM+SHAM acupoint(LIM+SHAM)group,and LIM+EA group.Animals in the NC group received no intervention,while those in other three groups were covered with-6.0 diopter(D)lenses on right eyes.Meanwhile,animals in the LIM+EA group received EA at Hegu(LI4)combined with Taiyang(EX-HN5)acupoints,while those in the LIM+SHAM group were treated at sham points.After treatments for 1,2,and 4wk,morphological changes in ciliary muscles were observed with hematoxylin and eosin(H&E)staining and nick end labeling(TUNEL),and the expression of the mitochondrial apoptotic signaling pathway-related molecules in ciliary muscles was measured by real-time quantitative polymerase chain reaction(qPCR)and Western blot.Additionally,the adenosine triphosphate(ATP)contents were also determined in ciliary muscles.RESULTS:Axial length increased significantly in the LIM and LIM+SHAM groups and decreased in the LIM+EA group.The ciliary muscle fibers were broken and destroyed in both LIM and LIM+SHAM groups,whereas those in the LIM+EA group improved significantly.TUNEL assay showed the number of apoptotic cells increased in the LIM and LIM+SHAM groups,whereas reduced in the LIM+EA group.ATP contents showed a significant decrease in the LIM and LIM+SHAM groups,whereas increased after EA treatment.Compared with the NC group,the dynamin-related protein 1(DRP1),Caspase3,and apoptotic protease activator 1(APAF1)levels were significantly increased in the LIM group and decreased in the LIM+EA group.CONCLUSION:The results provide evidence of EA inhibiting the development of myopia by regulating the mitochondrial apoptotic signaling pathway.

Analysis of clinical and pathological features of ciliary body medulloepithelioma

AIM:To analyze and summarize the clinical and pathological features of ciliary body medulloepithelioma.METHODS:The clinical and pathological data of 11 patients(11 eyes) who were diagnosed with ciliary body medulloepithelioma at Beijing Tongren Hospital,Capital Medical University,from 2007 to 2021 were retrospectively analyzed.RESULTS:The initial symptoms of 11 patients included vision loss(6 eyes),atrophia bulbi(1 eye),proptosis(2 eyes),and leukocoria(2 eyes).Most patients suffered with corneal opacity,anterior chamber flare and hyphema.Iris neovascularization and synechia,complicated cataract,and secondar y glaucoma occurred in several cases.Three patients even had lens subluxation and retinal detachment.B-scan ultrasonography showed vitreous opacity and a medium-high uneven echo mass in the eyeball.Ultrasound biomicroscopy examination showed a spherical or hemispherical ciliary body mass with uneven internal echoes and irregular cystic spaces.All of the 11 patients were diagnosed with malignant ciliary body medulloepithelioma by pathological evidence.In this study,6 patients had enucleation(2 patients had systemic chemotherapy after surgery),and the other 5 patients had local tumor resection(1 patient had plaque radiotherapy after surgery).CONCLUSION:Ciliary body medulloepithelioma is a rare intraocular tumor and may be easily confused with retinoblastoma.Analyzing the clinical and pathological features of ciliary body medulloepithelioma is useful to further understand ciliary body medulloepithelioma,and can make an accurate diagnosis and better treatment.

Haemoglobin Measurement from Eye Anterior Ciliary Arteries through Borescope Camera

Nowadays,smartphones are used as self-health monitoring devices for humans.Self-health monitoring devices help clinicians with big data for accurate diagnosis and guidance for treatment through repetitive measurement.Repetitive measurement of haemoglobin requires for pregnant women,pediatric,pulmonary hypertension and obstetric patients.Noninvasive haemoglobin measurement through conjunctiva leads to inaccurate measurement.The inaccuracy is due to a decrease in the density of goblet cells and acinar units in Meibomian glands in the human eye as age increases.Furthermore,conjunctivitis is a disease in the eye due to inflammation or infection at the conjunctiva.Conjunctivitis is in the form of lines in the eyelid and covers the white part of the eyeball.Moreover,small blood vessels in eye regions of conjunctiva inflammations are not visible to the human eye or standard camera.This paper proposes smartphone-based hae-moglobin(SBH)measurement through a borescope camera from anterior ciliary arteries of the eye for the above problem.The proposed SBH method acquires images from the anterior ciliary arteries region of the eye through a smartphone attached with a high megapixel borescope camera.The anterior ciliary arteries are projected through transverse dyadic wavelet transform(TDyWT)and applied with delta segmentation to obtain blood cells from the ciliary arteries of the eye.Furthermore,the Gaussian regression algorithm measures haemoglobin(Hb)with more accuracy based on the person,eye arteries,red pixel statistical parameters obtained from the left and right eye,age,and weight.Furthermore,the experimen-tal result of the proposed SBH method has an accuracy of 96%in haemoglobin measurement.

Effect of ciliary neurotrophic factor on activation of astrocytes in vitro

Objective To observe the activating effect of ciliary neurotrophic factor （CNTF） on astrocyte in vitro. Methods Astrocytes cultured purely from newborn rats. Cerebral cortex was raised in normal and serum deprivation condition with different concentrations （in ng/ml： 0, 2, 20, or 200） of CNTF. After cultured for 24 h, the shape and the cell cycle of astrocytes were examined by immunocytochemistry and flow cytometer, respectively. Results The immunoactivity of glial fibrillary acidic protein （GFAP） and the nuclear size of astrocytes were increased when CNTF was applied, whether cells were cultured in medium with or without serum. CNTF promoted astrocytes to enter the cell cycle in medium with serum, but had no this effect in medium without serum. Conclusion In medium without serum, astrocytes could differentiate into activated state ceils with CNTF application, but could not proliferate; in medium with serum, astrocytes could proliferate with aid of CNTF.

Safety and efficacy of ultrasound ciliary plasty as a primary intervention in glaucoma patients

AIM: To evaluate the safety and the efficacy of the ultrasound ciliary plasty(UCP) on the intraocular pressure(IOP) control in glaucomatous eyes without previous glaucoma surgery.METHODS: A retrospective study included patients with primary and secondary glaucoma who underwent UCP in Dar Al Shifa Hospital, Kuwait between January 2017 to June 2018. High-intensity focused ultrasound procedures were performed under peribulbar anesthesia using the 2^(nd) generation probe with 8 s duration of each of the 6 shots. Complete ophthalmologic examinations were scheduled pre-treatment, and at 1 d, 1 wk, 1, 3, 6 and 12 mo posttreatment. Primary outcomes were the IOP reduction and success rates at 12 mo, while the secondary outcomes were the occurrence of vision threatening complications and visual acuity.RESULTS: The records of 62 eyes of 62 patients were analyzed with mean age of 63.8 y(67.7% males). There was statistically significant reduction in the mean IOP from 35.2±8.3 mm Hg before treatment to 20.6±8.7 mm Hg at 12^(th) month(P<0.0005) with a mean percentage IOP reduction of 42.3% with significant reduction in the mean number of antiglaucomatous drugs from 3.2±0.4 before treatment to 2.1±1.02 at 12 mo(P<0.0005). Qualified success was achieved in 77.4% of eyes at 12 mo. No major intra-or posttreatment complications were reported.CONCLUSION: Second-generation UCP prove to be effective in reducing IOP in naive glaucoma patients with lower success rates in cases of neovascular and uveitic glaucomas.

Management of primary ciliary dyskinesia/Kartagener＇s syndrome in infertile male patients and current progress in defining the underlying genetic mechanism

Kartagener＇s syndrome （KS） is an autosomal recessive genetic disease accounting for approximately 50% of the cases of primary ciliary dyskinesia （PCD）. As it is accompanied by many complications, PCD/KS severely affects the patient＇s quality of life. Therapeutic approaches for PCD/KS aim to enhance prevention, facilitate rapid definitive diagnosis, avoid misdiagnosis, maintain active treatment, control infection and postpone the development of lesions. In male patients, sperm flagella may show impairment in or complete absence of the ability to swing, which ultimately results in male infertility. Assisted reproductive technology will certainly benefit such patients. For PCD/KS patients with completely immotile sperm, intracytoplasmic sperm injection may be very important and even indispensable. Considering the number of PCD/KS susceptibility genes and mutations that are being identified, more extensive genetic screening is indispensable in patients with these diseases. Moreover, further studies into the potential molecular mechanisms of these diseases are required. In this review, we summarize the available information on various aspects of this disease in order to delineate the therapeutic objectives more clearly, and clarify the efficacy of assisted reproductive technology as a means of treatment for patients with PCD/KS-associated infertility.

Chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor promotes sciatic nerve repair

A chemically extracted acellular allogeneic nerve graft can reduce postoperative immune rejection, similar to an autologous nerve graft, and can guide neural regeneration. However, it remains poorly understood whether a chemically extracted acellular allogeneic nerve graft combined with neurotrophic factors provides a good local environment for neural regeneration. This study investigated the repair of injured rat sciatic nerve using a chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor. An autologous nerve anastomosis group and a chemical acellular allogeneic nerve bridging group were prepared as controls. At 8 weeks after repair, sciatic functional index, evoked potential amplitude of the soleus muscle, triceps wet weight recovery rate, total number of myelinated nerve fibers and myelin sheath thickness were measured. For these indices, values in the three groups showed the autologous nerve anastomosis group 〉 chemically extracted acellular nerve graft ＋ ciliary neurotrophic factor group 〉 chemical acellular allogeneic nerve bridging group. These results suggest that chemically extracted acellular nerve grafts combined with ciliary neurotrophic factor can repair sciatic nerve defects, and that this repair is inferior to autologous nerve anastomosis, but superior to chemically extracted acellular allogeneic nerve bridging alone.

Biomechanical analysis of optic nerve injury treated by compound light granules and ciliary neurotrophic factor

In this study, rabbit models of optic nerve injury were reproduced by the clamp method. After modeling, rabbit models were given one injection of 50 ng recombinant human ciliary neurotrophic factor into the vitreous body and/or intragastric injection of 4 g/kg compound light granules containing Radix Angelicae Sinensis and Raidix Paeoniae Alba at 4 days after modeling, once per day for 30 consecutive days. After administration, the animals were sacrificed and the intraorbital optic nerve was harvested. Hematoxylin-eosin staining revealed that the injured optic nerve was thinner and optic nerve fibers were irregular. After treatment with recombinant human ciliary neurotrophic factor, the arrangement of optic nerve fibers was disordered but they were not markedly thinner. After treatment with compound light granules, the arrangement of optic nerve fibers was slightly disordered and their structure was intact. After combined treatment with recombinant human ciliary neurotrophic factor and compound light granules, the arrangement of optic nerve fibers was slightly disordered and the degree of injury was less than after either treatment alone. Results of tensile mechanical testing of the optic nerve showed that the tensile elastic limit strain, elastic limit stress, maximum stress and maximum strain of the injured optic nerve were significantly lower than the normal optic nerve. After treatment with recombinant human ciliary neurotrophic factor and/or compound light granules, the tensile elastic limit strain, elastic limit stress, maximum stress and maximum strain of the injured optic nerve were significantly increased, especially after the combined treatment. These experimental findings indicate that compound light granules and ciliary neurotrophic factor can alleviate optic nerve injury at the histological and biochemical levels, and the combined treatment is more effective than either treatment alone.

Protective effects of ciliary neurotrophic factor on the retinal ganglion cells by injure of hydrogen peroxide

AIM： To explore the effect of ciliary neurotrophic factor （CNTF） on retinal ganglion cell （RGC）-5 induced by hydrogen peroxide （H2O2）. METHODS： After cell adherence, RGC-5 culture medium was changed to contain different concentrations of H2O2 from 50 to 150 μmol/L at four time points （0.5, 1, 1.5 and 2h） to select the concentration and time point for H2O2 induced model. Two different ways of interventions for injured RGC-5 cells respectively were CNTF as an addition in the culture medium or recombinant lentiviral plasmid carrying CNTF gene transfecting bone mesenchymal stem cells （BMSCs） for co-culture with RGC-5. RESULTS： Compared to the control group, H2O2 led to RGC-5 death closely associated with concentrations and action time of H2O2 and we chose 125 μmol/L and 2h to establish the H2O2-induced model. While CNTF inhibited the loss of RGC-5 cells obviously with a dose-dependent survival rate. Nevertheless two administration routes had different survival rate yet higher rate in recombinant lentiviral plasmid group but there were no statistically significant differences. CONCLUSION： Both the two administration routes of CNTF have effects on RGC-5 cells induced by H2O2. If their own advantages were combined, there may be a better administration route.

Case Report:Adenoma of nonpigmented epithelium in ciliary body:literature review and case report

Adenomas of the nonpigmented ciliary epithelium (NPCE) are often clinically indistinguishable from amelanotic malignant melanomas of the ciliary body or metastatic carcinomas. This paper reports a case study of a distinctive variant of adenoma of the NPCE, which clinically appears as epiretinal membrane in the macular region. Histopathologic studies have revealed this is an adenoma of the NPCE. Identification of this clinic feature is important because it will miss the diagnosis of the adenoma of the NPCE. In this case study, B-scan ultrasonography as well as computerized tomography (CT) has been used to provide help in diagnosing the ciliary body tumor. Because of their anterior location in the ciliary body, partial lamellar sclerou-vectomy is an effective method of treatment.

Influence of endogenous ciliary neurotrophic factor on neural differentiation of adult rat hippocampal progenitors

Ciliary neurotrophic factor is the only known neurotrophic factor that can promote differentiation of hippocampal neural progenitor cells to glial cells and neurons in adult rats. This process is similar to spontaneous differentiation. Therefore, ciliary neurotrophic factor may be involved in spontaneous differentiation of neural stem cells. To verify this hypothesis, the present study isolated neural progenitor cells from adult male rats and cultured them in vitro. Results showed that when neural progenitor cells were cultured in the absence of mitogen fibroblast growth factor-2 or epidermal growth factor, they underwent spontaneous differentiation into neurons and glial cells. Western blot and immunocytochemical staining showed that exogenous ciliary neurotrophic factor strongly induced adult hippocampal progenitor cells to differentiate into neurons and glial cells. Moreover, passage 4 adult hippocampal progenitor cells expressed high levels of endogenous ciliary neurotrophic factor, and a neutralizing antibody against ciliary neurotrophic factor prevented the spontaneous neuronal and glial differentiation of adult hippocampal progenitor cells. These results suggest that the spontaneous differentiation of adult hippocampal progenitor cells is mediated partially by endogenous ciliary neurotrophic factor.

Ultrasound biomicroscopic imaging demonstrate thinner ciliary body thickness in eyes with angle closure

·AIM:To compare the ciliary body thickness between eyes with primary angle closure(PAC)and primary angle-closure glaucoma(PACG)with the normal eyes,and to investigate the association between ciliary body thickness and ciliary processes situation.·METHODS:In this cross-sectional study,57 patients with PAC/PACG were matched to 57 normal subjects after propensity score matching(PSM)adjusting for age and gender.All subjects underwent conventional ocular examinations and ultrasound biomicroscopy(UBM)examination,among which the patients with PAC/PACG performed the examinations one month after laser peripheral iridotomy(LPI).Quantitative parameters were measured,which included ciliary body thickness at the position of 1 mm posterior to the scleral spur(CBT1),trabecular-ciliary process distance(TCPD)and trabecularciliary process angle(TCA).·RESULTS:Eyes with PAC/PACG presented significantly thinner CBT1,shorter TCPD and smaller TCA(P<0.001)than the normal eyes,both in comparison of the means of four quadrants and in comparisons of each quadrant.After removing images with peripheral anterior synechia(PAS),the same results were also found in comparisons between the two groups.Significant correlations were found between TCPD(R~2=0.537,P<0.001)and TCA(R~2=0.517,P<0.001)with CBT1.·CONCLUSION:Eyes with PAC/PACG have thinner ciliary body thickness and more anteriorly situated ciliary processes.Thinner ciliary body thickness is associated with anterior situation of the ciliary processes.

Clinical spectrum of primary ciliary dyskinesia in childhood

Although the triad of bronchiectasis, sinusitis and situs inversus was first described by Kartagener in 1933, the clinical spectrum of primary ciliary dyskinesia is still under investigation. Heterotaxy defects as well as upper and lower respiratory tract symptoms are the main manifestations in childhood. It is now recognized that situs inversus is encountered in only half of patients. The first lower respiratory symptoms may be present from infancy as neonatal respiratory distress. The most common lower airway manifestations are chronic wet cough, recurrent pneumonia and therapy resistant wheezing. Patients are at risk of developing bronchiectasis which may even be the presenting finding due to delayed diagnosis. Upper respiratory tract infections such as nasal congestion, nasal drainage and recurrent sinusitis as well as otologic manifestations such as otitis media or otorrhea with conductive hearing loss are also often encountered. It seems that the type of ciliary ultrastructure defects and the involved mutated genes are associated to some extent to the clinical profile. The disease, even in nowadays, is not recognized at an early age and the primary care clinician should have knowledge of its clinical spectrum in order to select appropriately the children who need further investigation for the diagnosis of this disorder.

Thermal and concentration analysis of Phan-Thien-Tanner fluid flow due to ciliary movement in a peripheral layer

This paper presents the analysis of two-layer cilia induced flow of Phan-Thien-Tanner(PTT) fluid with thermal and concentration effect.The Phan-Thien-Tanner fluid model has been used in the analogy of mucus present in the respiratory tract.The two-layer model approach was used due to the Peri Ciliary liquid Layer(PCL) and Airway Ciliary Layer(ACL) present on the epithelium cell in respiratory tract.The mathematical modelling of two-layer flow problem was simplified using long wavelength and small Reynold ’ s number approximation.The resulting differential equation with moving boundary gives exact solution for velocity,temperature and concentration profiles in two layers.The change in pressure has calculated by the results of velocity profile,also the pressure rise was evaluated by the numerical integration of pressure gradient along the channel wall.The impact of physical parameters on pressure rise,velocity,temperature and concentration profile was explained by the graphs.It can be seen from graphs that velocity and temperature profile are maximum in the inner layer of fluid(PCL) and concentration profile is maximum at outer layers of fluid(ACL).

In vitro neuroprotective effects of ciliary neurotrophic factor on dorsal root ganglion neurons with glutamate-induced neurotoxicity

Ciliary neurotrophic factor has neuroprotective effects mediated through signal transducer and Janus kinase（JAK） 2/activator of transcription 3（STAT3） and phosphatidylinositol 3-kinase（PI3 K）/Akt signaling pathways.Whether ciliary neurotrophic factor is neuroprotective for glutamate-induced excitotoxicity of dorsal root ganglion neurons is poorly understood.In the present study,the in vitro neuroprotective effects of ciliary neurotrophic factor against glutamate-induced excitotoxicity were determined in a primary culture of dorsal root ganglion neurons from Wistar rat embryos at embryonic day 15.Whether the JAK2/STAT3 and PI3 K/Akt signaling pathways were related to the protective effects of ciliary neurotrophic factor was also determined.Glutamate exposure inhibited neurite outgrowth,cell viability,and growth-associated protein 43 expression and promoted apoptotic neuronal cell death,all of which were reversed by the administration of exogenous ciliary neurotrophic factor.Additionally,preincubation with either JAK2 inhibitor AG490 or PI3 K inhibitor LY294002 blocked the neuroprotective effect of ciliary neurotrophic factor.These data indicate that the two pathways JAK2/STAT3 and PI3 K/Akt play major roles in mediating the in vitro neuroprotective effects of ciliary neurotrophic factor on dorsal root ganglion neurons with glutamate-induced neurotoxicity.

CCNO mutation as a cause of primary ciliary dyskinesia:A case report

BACKGROUND Primary ciliary dyskinesia(PCD)is an uncommon and genetically diverse condition.According to reports,most patients had more than 50 visits before being diagnosed with PCD,and the age at diagnosis was mostly in preschool,with an average age of about(10.9±14.4)years old.CCNO is a pathogenic gene that regulates the cell cycle,and its mutation is linked to the uncommon human genetic disorder PCD.Although the prevalence of the CCNO mutation is regarded to be exceptionally low,new reports of this mutation have increased in comparison to prior ones.PCD patients with CCNO are rare,and the incidence rate is no more than 2%in whole PCD patients.CASE SUMMARY Here,we report a case of a young Chinese woman diagnosed with PCD,who was found to carry the CCNO gene by whole exon gene sequencing.In this case,a young non-smoking Chinese female exhibiting recurrent cough and sputum at birth.Chest computed tomography(CT)showed bronchiectasis with infection,and sinus CT showed chronic sinusitis.However,the patient had no visceral transposition and no history of infertility.Under electron microscope,it was found that cilia were short and reduced in number,and no power arm of cilia was observed.Whole exon sequencing analysis of the genome of the patient showed that the patient carried CCNO pathogenic gene,exon c.303C>A nonsense mutation and c.248_252dup frameshift mutation.Her clinical symptoms and CT images were improved after two months of treatment with aerosol inhalation and oral azithromycin.CONCLUSION The results showed that CCNO is an important cause of PCD.More mutant genes that may contribute to genetically diverse disorders like PCD have been discovered as sequencing technology has advanced.Furthermore,the increase of genetic information makes it easier to diagnose uncommon diseases in clinical practice.

Extracting intraocular foreign body at or near the ciliary body with scleral indentation in direct visualization

Dear Editor,I＇m Dr. Qing-Huai Liu from Department of Ophthalmology, the First Affiliated Hospital of Nanjing Medical University,Nanjing, China. I write to present four cases diagnosed with the intraocular foreign body （IOFB） at or near the ciliary body and to evaluate the effect of extracting IOFB with scleral indentation in direct visualization.

Genetic defects in ciliary genes in autosomal dominant polycystic kidney disease

AIM To evaluate the genetic defects of ciliary genes causing the loss of primary cilium in autosomal dominant polycystic kidney disease(ADPKD). METHODS We analyzed 191 structural and functional genes of the primary cilium using next-generation sequencing analysis. We analyzed the kidney samples, which were obtained from 7 patients with ADPKD who underwent nephrectomy. Each sample contained polycystic kidney tissue and matched normal kidney tissue. RESULTS In our study, we identified genetic defects in the 5 to 15 genes in each ADPKD sample. The most frequently identified defects were found in genes encoding centrosomal proteins (PCM1, ODF2, HTT and CEP89) and kinesin family member 19 (KIF19), which are important for ciliogenesis. In addition, pathogenic mutations in the PCM1 and KIF19 genes were foundin all ADPKD samples. Interestingly, mutations in the genes encoding the intraflagellar transport proteins, which are the basis of animal models of ADPKD, were only rarely detected. CONCLUSION The results of our study revealed the actual state of structural ciliary genes in human ADPKD tissues and provided valuable indications for further research.

Effect of ciliary neurotrophic factor on bcl-2 and c-jun gene and protein expression in cultured retinal nerve cells

BACKGROUND：In various retinal neurodegenerative animal models,ciliary neurotrophic factor （CNTF） exhibits prominent neuroprotective effects on retinal nerve cells.Bcl-2 is an anti-apoptotic protein.c-Jun is upregulated and phosphorylated in the activated c-Jun N-terminal kinase pathway,which subsequently mediates apoptosis.However,the effect of CNTF on Bcl-2 and c-Jun expression in retinal nerve cells remains unclear.OBJECTIVE：To determine the dynamic changes in retinal nerve cell apoptosis,as well as bcl-2 and c-jun gene and protein expression,following a single dose of CNTF in a short period of time.DESIGN,TIME AND SETTING：A single-blind,randomized,controlled,in vitro experiment was performed at the Central Laboratory of Beijing Tongren Hospital from May 2008 to April 2009.MATERIALS：Neonatal bovine retinal nerve cells （Chinese Holstein）,recombinant human CNTF （PeproTech,Rocky Hill,NJ,USA）,rabbit polyclonal anti-Bcl-2 and c-Jun antibodies （Abeam,Cambridge,UK）,fluorescein isothiocyanate-conjugated annexin V/propidium iodide kit （BioVision,Mountain View,CA,USA）,real time polymerase chain reaction instrument （ABI,Foster City,CA,USA）,and flow cytometer （BD FACSCalibur,Franklin Lakes,NJ,USA）.METHODS：Neonatal bovine retinal cells from passage 2 were cultured for 3 days and incubated with,or without,50 ng/mL CNTF （control）.MAIN OUTCOME MEASURES：Cell apoptosis was detected via Annexin V-FITC/PI double-staining and flow cytometry.bcl-2 and c-jun mRNA and protein expression were detected by quantitative real time polymerase chain reaction and western blot analysis.RESULTS：The proportion of late-stage apoptotic cells was significantly decreased at 2,4,and 6 days after CNTF treatment compared with the control group （P 〈 0.01）.CNTF did not alter bcl-2 mRNA expression at the three time points,but significantly increased Bcl-2 protein expression at 2 and 4 days （P 〈 0.01）.c-jun mRNA expression was significantly decreased 4 days after CNTF treatment （P〈 0.01）.In addition,c-Jun protein expression was slightly increased at 4 days （P〈 0.01）,but decreased at 6 days,compared with the control group （P〈 0.05）.CONCLUSION：A single dose of CNTF （50 ng/mL） upregulated Bcl-2 protein and downregulated c-jun mRNA expression,followed by a parallel,but lagged,change in c-Jun protein production in cultured neonatal bovine retinal nerve cells.These results suggested that CNTF reduces retinal nerve cell apoptosis by modifying Bcl-2 and c-Jun expression.