Au nanostar nanoparticle as a bio-imaging agent and its detection and visualization in biosystems.

In the present work, we report the imaging of Au nanostars nanoparticles (AuNSt) and their multifunctional applications in biomedical research and theranostics applications. Their optical and spectroscopic properties are considered for the multimodal imaging purpose. The AuNSt are prepared by the seed-meditated method and characterized for use as an agent for bio-imaging. To demonstrate imaging with AuNSt, penetration and localization in different biological models such as cancer cell culture (A549 lung carcinoma cell), 3D tissue model (multicellular tumor spheroid on the base of human oral squamous carcinoma cell, SAS) and murine skin tissue are studied. AuNSt were visualized using fluorescence lifetime imaging (FLIM) at two-photon excitation with a pulse duration 140 fs, repetition rate 80 MHz and 780 nm wavelength femtosecond laser. Strong emission of AuNSt at two-photon excitation in the near infrared range and fluorescence lifetime less than 0.5 ns were observed. It allows using AuNSt as a fluorescent marker at two-photon fluorescence microscopy and lifetime imaging (FLIM). It was shown that AuNSt can be observed inside a thick sample (tissue and its model). This is the first demonstration using AuNSt as an imaging agent for FLIM at two-photon excitation in biosystems. Increased scattering of near-infrared light upon excitation of AuNSt surface plasmon oscillation was also observed and rendered using a possible contrast agent for optical coherence tomography (OCT). AuNSt detection in a biological system using FLIM is compared with OCT on the model of AuNSt penetrating into animal skin. The AuNSt application for multimodal imaging is discussed.

Phagocytosis and immune response studies of Macrophage-Nanodiamond Interactions in vitro and in vivo.

The applications of nanodiamond as drug delivery and bio-imaging can require the relinquishing ND-drug conjugate via blood flow, where interaction with immune cells may occur. In this work, we investigated the ND penetration in macrophage and the immune response using the tissue-resident murine macrophages (RAW 264.7). Confocal fluorescence imaging, immunofluorescence analysis of nuclear translocation of interferon regulatory factor IRF-3 and transcriptional factor NF-κΒ, analysis of pro-inflammatory cytokines production IL-1ß, IL-6 IL-10 with a reverse transcription-polymerase chain reaction technique were applied. The TNF-α factor production has been studied both in vitro at ND interaction with the macrophage and in vivo after ND injection in the mice blood system using immunoassay. The macrophage antibacterial function was estimated through E. coli bacterial colony formation. ND didn't stimulate the immune response and functionality of the macrophage was not altered. Using MTT test, ND was found negligibly cytotoxic to macrophages. Thus, ND can serve as a biocompatible platform for bio-medical applications. Left: Graphic representation of Nanodiamond internalization in macrophage. Right: (a) Fluorescence images of lysosomes, (b) nanodiamond and (c) merged image of nanodiamond internalization in macrophage.

Nanodiamond for biolabelling and toxicity evaluation in the zebrafish embryo in vivo.

Nanodiamond (ND) has been proposed for various biomedical applications, including bioimaging, biosensing and drug delivery, owing to its physical-chemical properties and biocompatibility. Particularly, ND has been demonstrated as fluorescence- and Raman-detectable labels in many cellular models. Different surface functionalization methods have been developed, varying the ND's surface properties and rendering the possibility to attach biomolecules to provide interaction with biological targets. For this, toxicity is of major concern in animal models. Aside from cellular models, a cost-effective animal test will greatly facilitate the development of applications. In this study, we use the rapid, sensitive and reproducible zebrafish embryo model for in vivo nanotoxicity test. We optimize the conditions for using this animal model and analyze the zebrafish embryonic development in the presence of ND. ND is observed in the embryo in vivo using laser confocal fluorescence microscopy and fluorescence lifetime imaging. Using the zebrafish model for a safety evaluation of ND-based nanolabel is discussed.

Early statin therapy in patients with acute intracerebral hemorrhage without prior statin use.

BACKGROUND AND PURPOSE: Statin therapy is beneficial for primary and secondary prevention of ischaemic stroke, but its influence in patients with intracerebral hemorrhage (ICH) is unclear. An assessment was made of the effect of early statin therapy on patients with acute ICH. METHODS: Taiwan's National Health Insurance Research Database was screened for patients without prior statin therapy admitted from January to December 2008 for newly diagnosed ICH. Patients taking statins during hospitalization or within 3 months post-discharge were the early statin group (n = 749); patients who were not were the control group (n = 7583). The study end-points were recurrent ICH and all-cause mortality during follow-up. RESULTS: All eligible patients were followed up until 31 December 2010. During the follow-up, 69 (9.2%) patients in the early statin group and 677 (8.9%) control group patients had recurrent ICH. Cox proportional hazards analyses showed that early statin use did not increase the risk of recurrent ICH (adjusted hazard ratio 1.044; 95% confidence interval 0.812-1.341). During the same period, 90 (12.0%) of the early statin group and 1519 (20.0%) control group patients died. All-cause mortality was lower in the early statin group (adjusted hazard ratio 0.742; 95% confidence interval 0.598-0.919) than in the control group. Matched propensity score analyses were consistent with findings in Cox proportional hazards analyses. CONCLUSIONS: Early statin group patients with acute ICH did not have a higher recurrent risk of ICH and might have lower all-cause mortality during follow-up. It is concluded that statin therapy might be beneficial for patients with ICH.

Reduction of bladder activity on FDG PET/CT scan in patients with urinary bladder carcinoma. A prospective study with a patient-friendly protocol.

UNLABELLED: Oral hydration with large volume of fluid, high dose of diuretics and maximum bladder distension are frequently required to achieve an adequate urinary FDG clearance in an FDG PET/CT protocol for bladder cancer or pelvic tumour evaluation. Although most patients tolerated these procedures for eliminating urinary FDG activity, these procedures may be still unpleasant. AIM: Is there a more patient-friendly protocol which is less burdensome and yet provides a satisfactory FDG clearance in urine? In this study, we established a patient-friendly FDG PET/CT protocol without compromising urinary FDG clearance. PATIENTS, METHODS: 23 patients with biopsy-proven urinary bladder cancers were recruited to evaluate the effectiveness of this patient-friendly protocol on reducing urinary bladder FDG activity. The patient-friendly protocol includes encouraging patients to take a tolerable amount of fluid, delaying the administration of low dose diuretic, shortening the urine holding time and using delayed imaging. RESULTS: All of the patients tolerated this patient-friendly procedure well. In addition, the patient-friendly protocol was effective in reducing FDG activity in the urine. One hundred percent of primary bladder cancer were visualized on the FDG PET/CT images using this patient-friendly protocol. CONCLUSIONS: This patient-friendly FDG PET/CT protocol is less intrusive yet effective in reducing urinary FDG activity.

Impact of early statin therapy in patients with ischemic stroke or transient ischemic attack.

BACKGROUND: Statin therapy has demonstrated benefits in ischemic stroke patients. However, little is known about whether the timing of statin initiation affects clinical outcomes. The possible association of statin use and cerebral hemorrhage is also a concern for early statin therapy after stroke. The objective of this study was to evaluate the efficacy and safety of the initiation timing of statins in acute ischemic stroke. METHODS: A cohort study was performed using 5-year National Health Insurance Research Database in Taiwan. Patients without prior statin therapy admitted for their new ischemic stroke or transient ischemic attack (TIA) were enrolled. Patients were recognized as inhospital use group (2019 patients, statin initiation during hospitalization), intermediate use group (2266 patients, statin initiation within 1 year after discharge) or late use group (2958 patients, statin initiation 1 year later after discharge). The study endpoint was the composite outcome of ischemic stroke, TIA, hemorrhagic stroke, or acute coronary event. RESULTS: As compared with inhospital use, patients with late use had a 49% increased risk (adjusted HR: 1.49, 95% CI: 1.26-1.76) of composite endpoint. In contrast, patients with intermediate use had similar risk of endpoint as those with inhospital use. The risk of cerebral hemorrhage was similar in patients receiving inhospital, intermediate, or late statin treatment. CONCLUSIONS: In acute ischemic stroke, patients receiving late statin treatment carried a poorer clinical outcome than those with earlier statin initiation. Inhospital statin use after an acute ischemic stroke did not increase the risk of cerebral hemorrhage.

Update on diversity and distribution of HIV-1 subtypes in Yunnan province.

The aim of this study was to characterize updated HIV subtypes in Yunnan to determine their origins and distribution within the population. RT-PCR of both the gag and env genes were sequenced from Yunnan province inhabitants newly diagnosed with HIV-1. Sequence data from 290 samples were used for statistical analysis of subtype distribution and phylogenetic tree construction. Distribution data were adjusted to account for different geographical distributions of HIV-1 subtypes in the population. Phylogenetic analysis revealed six HIV-1 subtypes in Yunnan, including eight types of unique recombination forms (URFs). The most prevalent subtypes in this province, CRF07_BC (18·9%), CRF08_BC (39·1%), CRF01_AE (22·4%), and URFs (subtype C, 5·9% and subtype B, 4·5%), were all recombinants. We found significant differences in the distribution of these HIV-1 subtypes not only geographically, but also between various ethnic groups and with respect to transmission routes. Our findings indicate a complex population of HIV-1 subtypes, URFs, and recombinant subtypes in Yunnan province. This diversity could make the prevention and control of HIV infection in Yunnan more difficult due to the possibility of virus recombination or infection by multiple subtypes.

Universal pharmacological thromboprophylaxis for total knee arthroplasty may not be necessary in low-risk populations: a nationwide study in Taiwan.

BACKGROUND: Thromboprophylaxis should be universally administered in major orthopedic surgery. However, epidemiology of venous thromboembolism (VTE) following major knee surgery in Asia is scarce. OBJECTIVE: To describe the use of thromboprophylaxis and calculate the incidence and risk factors of symptomatic VTE following major knee surgery in Taiwan. METHODS: We used Taiwan's National Health Insurance Research Database to retrospectively identify patients (≥45 years) who underwent major knee surgery from 1998 to 2007 and collected the medical records within 3 months after the discharge. Logistic regression analysis was used to determine the risk factors of symptomatic VTE after the surgery. RESULTS: We identified 113 844 patients (mean age, 69.0 ± 7.7 years; female, 75.2%) receiving major knee arthroplasties. The mean length of stay was 9.1 ± 3.3 days. The overall pharmacological thromboprophylaxis rate was 2.2%. The 3-month cumulative incidence of procedure-related symptomatic VTE was 0.46% (95% CI, 0.42­0.50%). The median time to the first post-operation VTE was 7 days, with 85.4% occurring within 2 weeks after the discharge.Logistic regression analysis showed that previous VTE, malignancy, heart failure and neurologic disorder with extremity paralysis or pararesis were independent risk factors (P < 0.05) for symptomatic VTE following major knee arthroplasties. CONCLUSIONS: The thromboprophylaxis rate is low, which may be due to the very low incidence of symptomatic VTE after the surgery in Taiwan. Most symptomatic VTE occurred within 2 weeks after the surgery. Universal thromboprophylaxis for knee arthroplasties may not be necessary in Taiwan, but it should be considered in some high-risk populations.

High bone marrow angiopoietin-1 expression is an independent poor prognostic factor for survival in patients with myelodysplastic syndromes.

BACKGROUND: Angiogenic factors have an essential role in normal and pathologic angiogenesis. However, the clinical implication of angiogenic factor expression in myelodysplastic syndromes (MDS) remains unclear. METHODS: In this study, we sought to investigate the prognostic impact of the expression of genes encoding angiopoietin-1 (Ang-1), Ang-2, the receptor Tie2, vascular endothelial growth factor-A (VEGF-A) and VEGF-C in the bone marrow (BM) in 208 patients with newly diagnosed primary MDS. RESULTS: BM Ang-1 expression was significantly higher in MDS patients, especially those with higher-risk subtypes, than in normal controls. With a median follow-up time of 32.9 months, the disease transformed to acute leukaemia more frequently in the patients bearing higher Ang-1 expression than in those with lower expression (31.5% vs 18.6%, P=0.023). The MDS patients with higher Ang-1 expression had shorter overall survival than those with lower expression (median 20.8±4.5 months vs 63.3±17.8 months, P<0.001). Multivariate analyses showed that higher Ang-1 expression was an independent unfavourable prognostic factor for overall survival. There was no impact of the expression of other angiogenic factors on survival. CONCLUSION: BM Ang-1 expression may serve as a new biomarker to predict clinical outcome in MDS patients.

Characterizing protein activities on the lysozyme and nanodiamond complex prepared for bio applications.

Recently, nanodiamond particles have attracted increasing attention as a promising nanomaterial for its biocompatibility, easy functionalization and conjugation with biomolecules, and its superb physical/chemical properties. Nanodiamonds are mainly used as markers for cell imaging, using its fluorescence or Raman signals for detection, and as carriers for drug delivery. For the success of these applications, the biomolecule associated with the nanodiamond has to retain its functionality. In this work, the protein activities of egg white lysozyme adsorbed on nanodiamond particles of different sizes is investigated. The lysozyme nanodiamond complex is used here as a protein model for analyzing its structural conformation changes and, correspondingly, its enzymatic activity after the adsorption. Fourier-transform infrared spectroscopy (FTIR) is used for the analysis of the sensitive protein secondary structure. To access the activities of the adsorbed lysozyme, a fluorescence-based assay is used. The process of adsorption is also analyzed using UV-visible spectroscopic measurements in combination with analysis of nanodiamond properties with FTIR, Raman spectroscopy, and ζ-potential measurements. It is found that the activity of lysozyme upon adsorption depends on the nanodiamond's size and surface properties, and that the nanodiamond particles can be selected and treated, which do not alter the lysozyme functional properties. Such nanodiamonds can be considered convenient nanoparticles for various bioapplications.

Direct peroral cholangioscopy using an ultraslim endoscope and overtube balloon-assisted technique: a case series.

Overtube balloon-assisted direct peroral cholangioscopy (POC) using an ultraslim endoscope may be an effective alternative to the conventional mother-baby endoscope system. A total of 14 patients with biliary diseases underwent direct POC with an ultraslim endoscope. The endoscope was successfully advanced into the bile duct in all 14 patients (100 %). The success rate of the POC was 92.9 % (13/14) on the criterion of reaching the hilum or stricture site. Endoscopic biopsy was performed in six patients. Cystic duct or residual common bile duct stones were removed successfully under direct endoscopic visualization in three patients. A diagnosis of malignant or indeterminate bile duct stricture was changed to benign lesion or stricture or normal biliary mucosa in eight of ten patients. Procedure-related biliary tract infection occurred in one patient. This series demonstrated that direct POC using an ultraslim endoscope is useful for both diagnosis and treatment.

Assessment of the clinical outcomes and cost-effectiveness of the management of systolic heart failure in Chinese patients using a home-based intervention.

This study was designed to assess the clinical effect of a home-based telephone intervention in Chinese heart failure patients. A total of 550 Chinese heart failure patients were enrolled into either (i) a group that received the usual standard of care (UC group); or (ii) a group that received a home-based heart failure centre management programme using nursing specialist-led telephone consultations (HFC group). The impact of the home-based intervention on admission rate, admission length and medical costs over 6 months was measured. Although the mean left ventricular ejection fraction in HFC patients was 29.3% compared with 34.8% in UC patients, the home-based intervention resulted in a significantly lower all-cause admission rate per person (HFC 0.60 +/- 0.77 times/person; UC 0.96 +/- 0.85 times/person), a shorter all-cause hospital stay (reduced by 8 days per person) and lower total 6-month medical costs (reduced by US$2682 per patient). These results suggest that the home-based intervention with nursing specialist-led telephone consultations may improve the clinical outcome and provide cost-savings for Chinese patients with heart failure.

Incidence and cumulative recurrence rates of venous thromboembolism in the Taiwanese population.

SUMMARY BACKGROUND: Little information is available on the epidemiology of venous thromboembolism (VTE) in Asian populations. OBJECTIVES: To investigate VTE incidence, VTE cumulative recurrence rates and risk factors for VTE recurrence among the adult Taiwanese population. METHODS: This population-based cohort study used the Taiwanese National Health Insurance claims databases to identify 5347 adult patients (2463 men, 46.1%) with VTE diagnosed in 2001 and 2002. We calculated the crude incidence of VTE and its recurrence. We also conducted a nested case-control study (n = 3576) among this population to estimate the association between VTE recurrence and exposure to potential VTE risk factors by conditional logistic regression. RESULTS: The crude incidence of VTE was 15.9 per 100,000 person-years, and its recurrence rate was 5.1% per person-year. During 11 566 person-years of follow-up, the cumulative rates of VTE recurrence at 6, 12, 24, 36 and 47 months were 6.7%, 9.4%, 12.4%, 13.9%, and 14.4%, respectively. By conditional logistic regression, histories of VTE [adjusted odds ratio (OR) 1.71, 95% confidence interval (CI) 1.32-2.16] or malignant neoplasm (adjusted OR 1.64, 95% CI 1.26-1.99), major extremity trauma (adjusted OR 2.76, 95% CI 1.82-4.52), serious neurologic diseases (adjusted OR 1.43, 95% CI 1.12-1.84) or undergoing major surgery (adjusted OR 4.57, 95% CI 1.72-12.50) were associated with higher risks of VTE recurrence. CONCLUSIONS: The incidence of VTE is lower in the Taiwanese population than in Caucasians. Most VTE recurrences occur within 12 months, but they continue to occur beyond 1 year. The VTE recurrences are associated with malignancy, history of VTE, and major surgery after a previous VTE.

Demonstrating the pharmacogenetic effects of angiotensin-converting enzyme inhibitors on long-term prognosis of diastolic heart failure.

The objective of this study was to evaluate the effects of angiotensin-converting enzyme (ACE) inhibitors and pharmacogenetic interaction on the survival of the patients with diastolic heart failure (DHF). A total of 285 subjects with DHF confirmed by echocardiography were recruited in the period between 1995 and 2003. Baseline characteristics (age, sex, prior history, medication, and echocardiographic findings) and genetic polymorphisms (ACE gene insertion/deletion (I/D) polymorphism; T174M, M235T, G-6A, A-20C, G-152A, and G-217A polymorphisms of the angiotensinogen (AGT) gene; and A1166C polymorphisms of the angiotensin II type I receptor (AT1R)) were collected and matched (by propensity score) in those who received and those who did not receive ACE inhibitors. The patients were followed up to 10 years. Kaplan-Meier curves and Cox regression models were used to demonstrate the survival trend. The 85 patients who received ACE inhibitors and the other 85 patients who did not were found to have comparable baseline characteristics and polymorphism distribution. Prescription of ACE inhibitors was associated with a significant decrease in overall mortality (hazard ratio (HR), 0.45; 95% confidence interval (CI), 0.24-0.83; P=0.01), and a lower rate of cardiovascular events at 4000 days (HR, 0.53; 95% CI, 0.32-0.90; P=0.02). In addition, ACE I/D gene D allele was associated with higher overall mortality as compared with the I allele (HR, 2.04; P=0.003). This effect was diminished in those who received ACE inhibitors. The use of ACE inhibitor was associated with a significant decrease in long-term mortality and cardiovascular events in the patients with DHF. Genetic variants in the renin-angiotensin system genes were also associated, but their effects could be modified by the use of ACE inhibitors.

An effective surface-enhanced Raman scattering template based on a Ag nanocluster-ZnO nanowire array.

An effective surface-enhanced Raman scattering (SERS) template based on a 3D hybrid Ag nanocluster (NC)-decorated ZnO nanowire array was fabricated through a simple process of depositing Ag NCs on ZnO nanowire arrays. The effects of particle size and excitation energy on the Raman scattering in these hybrid systems have been investigated using rhodamine 6G as a standard analyte. The results indicate that the hybrid nanosystem with 150 nm Ag NCs produces a larger SERS enhancement factor of 3.2 x 10(8), which is much higher than that of 10 nm Ag NCs (6.0 x 10(6)) under 532 nm excitation energy. The hybrid nanowire arrays were further applied to obtain SERS spectra of the two-photon absorption (TPA) chromophore T7. Finite-difference time-domain simulations reveal the presence of an enhanced field associated with inter-wire plasmon coupling of the 150 nm Ag NCs on adjacent ZnO nanowires; such a field was absent in the case of the 10 nm Ag NC-coated ZnO nanowire. Such hybrid nanosystems could be used as SERS substrates more effectively than assembled Ag NC film due to the enhanced light-scattering local field and the inter-wire plasmon-enhanced electromagnetic field.

Size-dependent surface CO stretching frequency investigations on nanodiamond particles.

In this work, the spectroscopic properties of surface functionalized nanodiamond particles are investigated via Fourier transform infrared spectroscopy. The functionalization of the nanodiamond surface was achieved chemically using strong acid treatment method. The size dependent C=O stretching frequency (between 1680 and 1820 cm(-1)) are studied for particle diameter sizes from the 5 to 500 nm range. The surface C=O stretching frequencies at approximately 1820 cm(-1), for large particle size (500 nm), down shifted to 1725 cm(-1) (5 nm) with decreasing particle sizes. We attributed the shift as a result of hydrogen bond formation between the COOH groups in the carboxylated nanodiamond surfaces. Particle size was characterized with dynamic light scattering method and surface morphology of the particles was investigated with scanning electron microscopy. The influence of pH value on C=O stretching frequency is also analyzed. This finding affords useful information for the studying of surface functionalized nanodiamonds with implications for their interaction with biomolecules.

Combination regimen in the treatment of chronic prostatitis.

The aim of the study was to report our experiences in the treatment of chronic prostatitis using combination regimen including ciprofloxacin, doxazosin, allopurinol and biofeedback perineal massage. From May 2003 to April 2004, 7 patients with NIH Category II-chronic bacterial prostatitis and 7 patients with NIH Category IIIA-inflammatory chronic pelvic pain syndrome were treated. The NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) was scored by the patient before and after the treatment, 6 months later. In Category II patients, the bacterial eradication rate was 71% after ciprofloxacin treatment during a follow-up of 6 months. The beneficial response rate to allopurinol, doxazosin and biofeedback perineal massage was 50%, 42% and 85%, respectively. In NIH Category IIIA patients, the individual beneficial response rate to ciprofloxacin, allopurinol, doxazosin and biofeedback perineal massage was 57%, 100%, 71% and 100%, respectively. Comparing pre-treatment and post-treatment results of the combination regimen, there was a statistically significant improvement in the 3 domains of pain score, urinary symptoms and quality of life impact of the NIH-CPSI. Combination regimen including ciprofloxacin, doxazosin allopurinol and biofeedback perineal massage in the treatment of chronic prostatitis is a safe and effective modality in our limited experience.

Effects of a calcineurin inhibitor, tacrolimus, on glutamate-dependent potentiation in pelvic-urethral reflex in anesthetized rats.

Effects of tacrolimus, a protein phosphatase 2B inhibitor, on the reflex plasticity between the pelvic afferent nerve fibers and the urethra were examined in urethane-anesthetized rats. Repetitive stimulation (1 Hz) induced a potentiation (0.9+/-0.2 and 10.5+/-1.6 spikes in control and repetitive stimulation groups, respectively, P<0.01, N=10) in the activities of the pelvic-urethral reflex. Intrathecal tacrolimus (0.1 mM, 10 microl, bolus) blocked repetitive stimulation-induced potentiation in pelvic-urethral reflex activities (3.2+/-0.9 spikes in tacrolimus group versus 10.5+/-1.6 spikes in repetitive stimulation group, P<0.01, N=10). Glutamate (intrathecal, 0.1 mM, 10 microl, bolus) and N-methyl-D-aspartic acid (intrathecal, 0.1 mM, 10 microl, bolus) both reversed the blocking effects exerted by tacrolimus on repetitive stimulation-induced pelvic-urethral reflex potentiation (15.0+/-1.4 spikes in glutamate group and 11.4+/-1.4 spikes in N-methyl-D-aspartic acid group versus 3.2+/-0.9 spikes in tacrolimus-treated repetitive stimulation group, P<0.01, N=7). In addition, the reversal effect elicited by these two agonists of glutamate receptors showed no statistical difference (P=NS, N=7). All these results demonstrated that tacrolimus could block glutamatergic N-methyl-D-aspartic acid receptor-mediated potentiation in pelvic-urethral reflex activities. This finding may be pathologically relevant in patients who take tacrolimus as immunosuppressant therapy. Whether tacrolimus will induce urine incontinence in such patients or not needs further investigation.

Light-induced retinal damage involves tyrosine 33 phosphorylation, mitochondrial and nuclear translocation of WW domain-containing oxidoreductase in vivo.

WW domain-containing oxidoreductase WOX1, also named WWOX or FOR, is a known proapoptotic protein and a candidate tumor suppressor. Stress stimuli activate WOX1 via tyrosine 33 (Tyr33) phosphorylation and translocation to the mitochondria and nuclei in vitro. Here, the potential role of WOX1 in light-induced retinal degeneration in vivo was investigated. WOX1 is expressed primarily in the inner retina at perinatal stages, whereas an enhanced expression of WOX1, along with its Tyr33 phosphorylation (p-WOX1), is shown specifically in the retinal ganglion cells in adults. Prolonged exposure of mature rats to constant, low-intensity light (500 lux) for 1-2 months resulted in substantial death of photoreceptors and the presence of activated microglia, astrocytes and Muller glial in the outer retina. However, the inner retina was not or barely affected. In the damaged inner and outer nuclear layers of rat retina, WOX1 and p-WOX1 were overly expressed. Also, WOX1 colocalized with fragments of opsin-positive cones. In rd mice with an inherited retinal deficiency, upregulation of WOX1 and p-WOX1 in degenerated retina was observed with age. By electron microscopy, a large number of immunogold particles of WOX1 and p-WOX1 were found in the damaged mitochondria and condensed nuclei of degenerating photoreceptors, indicating that WOX1 undergoes activation and translocation to these organelles. In contrast, little or no WOX1-positive particles were found in the Golgi apparatus. In conclusion, activated WOX1 is likely to exert apoptosis of neuronal cells in the outer retina during the light-induced injury and in mice with an inherited retinal defect.