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We conducted a study to assess the pressure difference between the aqueous and vitreous humors in rabbit eyes using a direct intraocular pressure (IOP) measurement method. A micro-optic-fiber pressure sensor was utilized for this purpose. Preliminary experiments with enucleated porcine eyes confirmed the sensor's accuracy in measuring both aqueous and vitreous humor pressure. The main study involved six healthy albino rabbits, where the sensor measured the pressure in the anterior chamber (aIOP) and posterior vitreous-cavity (pIOP). These measurements were compared to aIOP values obtained through rebound tonometry. Additionally, pre- and postoperative pressure comparisons were made after performing a vitrectomy. Results revealed a significant disparity between aqueous and vitreous humor pressures. Prior to vitrectomy, pIOP was 22.8 mmHg, over twice as high as aIOP (11.0 mmHg), but decreased to a similar level following the procedure. Comparison between the sensor measurements and rebound tonometry showed agreement in aIOP values. In conclusion, our study demonstrates that vitreous humor pressure is consistently higher than aqueous humor pressure, reaching the upper limit of normal IOP. Furthermore, vitrectomy effectively reduces pIOP, aligning it with aIOP. These findings contribute valuable insights into intraocular pressure dynamics and have implications for clinical interventions targeting ocular pressure regulation. [ABSTRACT FROM AUTHOR]

The pathogenesis of both diabetic retinopathy (DR) and rheumatoid arthritis (RA) has recently been considered to involve autoimmunity. Serum and synovial fluid levels of anti-type II collagen antibodies increase early after the onset of RA, thus inducing immune responses and subsequent hydrarthrosis and angiogenesis, which resemble diabetic macular edema and proliferative DR (PDR), respectively. We previously reported that DR is also associated with increased serum levels of anti-type II collagen antibodies. Retinal hypoxia in DR may induce pericytes to express type II collagen, resulting in autoantibody production against type II collagen. As the result of blood-retinal barrier disruption, anti-type II collagen antibodies in the serum come into contact with type II collagen around the retinal vessels. A continued loss of pericytes and type II collagen around the retinal vessels may result in a shift of the immune reaction site from the retina to the vitreous. It has been reported that anti-inflammatory M2 macrophages increased in the vitreous of PDR patients, accompanied by the activation of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, a key regulator of innate immunity. M2 macrophages promote angiogenesis and fibrosis, which might be exacerbated and prolonged by dysregulated innate immunity. [ABSTRACT FROM AUTHOR]

Purpose: To elucidate how factors associated with swimming affect the lacrimal ducts of swimmers. Study design: Prospective, interventional cohort study, Methods: Five hundred seventy four consecutive epiphora patients were surveyed via a questionnaire regarding details of their swimming-pool usage; i.e., frequency, swim-goggles' wear, and type of pool activity (i.e., swimming vs. waist-depth walking). In this cohort, all the swimmers over 20 years old with anatomical lacrimal duct obstruction underwent surgical reconstruction. The surgical success rates at 12-months postoperative were compared using multivariable logistic regression analyses between swimmer/non-swimmer patients, those with a history of high/low frequency of pool usage, and those with high/low amount of conjunctival contact with the swimming-pool water. Results: Of the patients with anatomical lacrimal duct obstruction, 6.4% were habitual swimmers; nasolacrimal duct obstruction was more common in the swimmers than in the non-swimmers' controls (89.1%/66.7%, P = 0.025). The success rate of lacrimal surgery for the swimmers with anatomical nasolacrimal duct obstruction was lower (60.6%) than of the non-swimmers (83.3%, P = 0.048). A receiver operating characteristic curve analysis of the frequency for the prediction of surgical failure showed that the threshold was 4 days/week. The success rate was statistically lower (26.7%) in the high-frequency swimmers compared to the low-frequency swimmers (88.9%, P = 0.037). However, no statistical difference in the high/low ocular surface contact to the swimming-pool water was observed (71.4%/57.7%, P = 0.56). Conclusion: Habitual swimmers have a high risk of nasolacrimal-duct damage retrogradely from the nasal cavity that lowers lacrimal surgery's success rate. [ABSTRACT FROM AUTHOR]

Purpose: The pathomechanism leading to retinal vein occlusion (RVO) is unclear. Mechanical compression, thrombosis, and functional contractions of veins are discussed as the reasons for the increased resistance of venous outflow. We evaluated changes in the retinal venous pressure (RVP) following intravitreal injection of anti-vascular endothelial growth factor (VEGF) agent to determine the effect on RVO-related macular edema. Methods: Twenty-six patients with RVO-related macular edema (16 branch RVOs [BRVOs] and 10 central RVOs [CRVOs], age 72.5 ± 8.8 years) who visited our hospital were included in this prospective study. Visual acuity (VA), intraocular pressure (IOP), central retinal thickness (CRT) determined by macular optical coherence tomography, and RVP measured using an ophthalmodynamometer were obtained before intravitreal injection of ranibizumab (IVR) and 1 month later. Results: Comparison of the BRVOs and CRVOs showed that VA was significantly improved by a single injection in BRVOs (P < 0.0001; P = 0.1087 for CRVOs), but CRT and RVP were significantly decreased without significant difference in IOP after the treatment in both groups (P < 0.0001). Conclusion: The anti-VEGF treatment resulted in a significant decrease in the RVP, but the RVP remained significantly higher than the IOP. An increased RVP plays a decisive role in the formation of macula edema, and reducing it is desirable. [ABSTRACT FROM AUTHOR]

Determine the impact of the mTOR inhibitor, rapamycin, on the hyperglycemia-induced expression of vascular endothelial growth factor (VEGF) and the production of reactive oxygen species (ROS) in retinal cells. Rats made hyperglycemic for 8 weeks by streptozotocin, as well as control rats, received i.p. rapamycin (1 mg/kg) for 3 days prior to immunostaining of their retinas with anti-VEGF and anti-glial fibrillary acidic protein (GFAP) and measuring retinal protein levels of VEGF and GFAP by Western blotting. In other experiments, flow cytometry analysis of ethidium fluorescence determined intracellular ROS levels in the absence or presence of rapamycin (1 μM) under normoglycemic (5.5 mM) and hyperglycemic (25 mM) conditions in a rat retinal Müller cell line (TR-MUL5) and primary human retinal microvascular endothelial cells (HRMECs). In the diabetic retina, VEGF was elevated and colocalized with the glial marker, GFAP, whose level was also elevated. Treatment with rapamycin inhibited the diabetes-induced VEGF and GFAP increases. We also found that raising extracellular glucose from 5.5 mM to 25 mM resulted in significant rapamycin-sensitive increases in the ROS levels of TR-MUL5 cells and HRMECs. In rat retina, rapamycin attenuates the diabetes-induced VEGF overexpression, and in cultured Müller cells and HRMECs, inhibits the hyperglycemia-induced boost ROS. [ABSTRACT FROM AUTHOR]

Purpose: The photopic negative response (PhNR) is a negative wave following the b-wave of the photopic electroretinogram (ERG). The PhNR originates from the retinal ganglion cells (RGCs), and it can be used to assess the function of RGCs noninvasively and objectively. The purpose of this study was to determine whether the relative amplitudes (affected/normal eye) of the PhNR are significantly correlated with the degree of the relative afferent pupillary defect (RAPD) in eyes with unilateral or asymmetrical damage of the optic nerve. Methods: The PhNRs of the full-field photopic ERGs were measured. In addition, videopupillography and automated perimetry were performed on 27 cases with asymmetrical optic nerve disorders including glaucoma. The differences of these assessments were expressed by the relative amplitudes of the PhNRs of the two eyes, the neutral density (ND) filter required to equate the amplitudes of the pupillary light reflexes between the two eyes, and differences of the mean defects (ΔMDs) of the sensitivities of the Humphrey visual fields. The correlations between these values were determined by linear regression analyses. Results: The relative PhNR amplitudes were significantly and negatively correlated with the ΔMDs (R2 = 0.58, P = 0.0001). In addition, the relative PhNR amplitudes were moderately but significantly and positively correlated with the RAPDs (R2 = 0.36, P = 0.002). Conclusion: The relative amplitudes of the PhNR of the affected eyes to the contralateral eyes indicate an asymmetric alteration of the RGCs, and they can be used to monitor the physiology of the RGCs objectively. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the thermal injuries caused by ultrasonic pars plana phacoemulsification and aspiration (PPPEA) using pig eyes. Method: Using a 20-gauge (G) vitrectomy system (Accurus®, Fragmatome; Alcon Laboratories) in both the 'open-tip' and 'closed-tip' techniques, PPPEA was performed in pig eyes and the subsequent thermal injuries generated around the scleral wound were measured by infrared thermal imaging (thermography). Post surgery, the state of the scleral wound was observed under a microscope, and a tissue slice containing the scleral wound was then prepared and observed under an optical microscope. Results: Thermography measurements revealed a slight temperature rise around the scleral wound in the open-tip case, yet a marked temperature rise in the closed-tip case. The scleral wound incision produced by the open tip was linear, while that produced by the closed tip was expanded. Histological examination revealed mild degeneration of the sclera around the wound in the open-tip case, yet marked tissue degeneration by thermal injuries in the closed-tip case. Conclusion: Our findings showed that in PPPEA, the temperature of the tip of a 20G vitrectomy system rapidly increases due to the closed-tip technique, thus producing obvious thermal damage to the scleral wound. In order to prevent thermal injuries to the scleral wound during PPPEA, it is important to shorten the time of ultrasonic oscillation during surgery as much as possible while the tip is occluded with nuclear fragments. [ABSTRACT FROM AUTHOR]

Purpose: Diabetic retinopathy (DR) involves a proliferation of vascular endothelial cells and loss of pericytes. There is a link among the action of protein kinase C (PKC) and insulin signaling. Thus, we investigated the differences between these cells in insulin receptor (IR) phosphorylation in DR. Methods: Retinas were removed from streptozotocin-induced diabetic or healthy rats, and IR expression levels were compared by immunoblot and immunohistochemistry. In vitro assays also were performed in order to determine the expressions of phosphorylated IR in both cells cultured under 5.5 or 25 mM glucose by immunoblot. Cell viability was determined in both cells cultured under different concentrations of phorbol myristate acetate (PMA), a PKC activator. To determine the involvement of the PI3 kinase pathway of IR, PMA with or without wortmannin-induced changes in Akt was also analyzed. Results: Immunoreactivity to the IR was decreased in diabetic retina. High glucose (25 mM) increased phosphorylated IR levels in endothelial cells but not in pericytes. PMA (1 nM or higher) induced death of pericytes, while endothelial cells were increased. PMA increased phosphorylated Akt in endothelial cells and decreased in pericytes. Wortmannin suppressed the PMA-induced phosphorylation of Akt in endothelial cells. Conclusions: The different responses to 25 mM glucose and PMA were observed between retinal endothelial cells and pericytes. Thus, IR phosphorylation is likely important for retinal vascular cells to survive in diabetic retina. [ABSTRACT FROM AUTHOR]

Purpose: Aquaporin 4 (AQP4), a water channel protein, is known to be expressed in retinal Müller cells. The purpose of this study was to determine the effects of VEGF and AQP4 channels on the volumetric changes in Müller cells. Methods: Retinas from diabetic rats and a cultured Müller cell line, TR-MUL5, were used in this study. Intravitreal injections of VEGF or PBS were performed on either streptozotocin (STZ)-induced diabetic or normoglycemic rats. Retinal sections were immunostained for anti-glial fibrillary acidic protein (GFAP), anti-AQP4, and anti-VEGF. VEGF protein levels from collected retinas were determined by western blot analysis. Volumetric changes and nitric oxide (NO) levels in cultured Müller cells were determined using flow cytometry (FACS), in the presence or absence of VEGF and TGN-020, a selective AQP4 inhibitor. Results: In the diabetic rat retina, VEGF immunoreactivity was concentrated in the internal retinal layers, and AQP4 immunoreactivity was higher than controls. The expressions of AQP4 were colocalized with GFAP. Protein levels of VEGF in the hyperglycemic rat retina were significantly higher than controls. FACS analyses showed that exposure to VEGF enlarged Müller cells, while exposure to TGN-020 suppressed the enlargement. Intracellular levels of NO were increased after exposure to VEGF, which was suppressed following the addition of TGN-020. Conclusion: The observed Müller cell swelling is mediated by VEGF and AQP4. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether P7C3-A20, a proneurogenic neuroprotective agent, can protect the retinal ganglion cells (RGCs) of rats from optic nerve crushing. Methods: The left optic nerve of 67 rats was crushed, and 5.0 mg/kg/day of P7C3-A20 (crush-P7C3) or its vehicle (crush-placebo) was injected intraperitoneally for 3 days from one day prior to the crushing. The protective effects were determined by the number of Tuj-1-stained RGCs and by the ratio of the mRNA levels of BAX/Bcl- 2 on day 7. The levels of NAD and NAD-related genes were also determined. Results: The density of RGCs was 2009.4 ± 57.7 cells/mm in the sham controls; it was significantly lower in the crush-placebo group at 979.7 ± 144.3 cells/mm ( P < 0.0001). The neuroprotective effects of P7C3-A20 was demonstrated by the significantly higher density of 1266.0 ± 193.1 cells/mm than in the crush-placebo group ( P = 0.01, Scheffe). After crushing the optic nerve the BAX/Bcl- 2 ratio was higher in the optic nerves and retina, application of P7C3-A20 significantly reduced this ratio. P7C3-A20 significantly increased the NAD level in the untouched optic nerves from 1.36 ± 0.05 to 1.59 ± 0.10 nmol/mg protein ( P = 0.02, t test). Crushing the optic nerve decreased the level to 1.27 ± 0.21 nmol/mg protein and P7C3-A20 preserved the level at 1.43 ± 0.10 nmol/mg protein. Crushing the optic nerve decreased the mRNA levels of Nampt and Sirt- 1 in the optic nerves, while P7C3-A20 significantly restored the levels. Conclusions: P7C3-A20 can protect RGCs from optic nerve crushing possibly through preserving the NAD levels in the optic nerves. [ABSTRACT FROM AUTHOR]

To evaluate the histopathological findings of idiopathic and secondary epithelial membranes (ERMs). This study involved 19 ERM cases that underwent pars plana vitrectomy (PPV). ERM specimens were obtained from each patient during PPV and immediately fixed in 10 % formalin. Paraffin sections were stained with hematoxylin eosin (HE) and immunohistochemical analysis was performed with glial fibrillary acidic protein (GFAP), Ki-67, CD34, and nestin antibodies. The 19 ERM cases included 11 idiopathic ERM cases and 8 secondary ERM cases i.e., 2 eyes that underwent PPV for retinal detachment and 6 eyes that underwent PPV for proliferative diabetic retinopathy. HE staining showed that some of the idiopathic ERM specimens consisted of internal limiting membrane. In contrast, numerous invasive cells were observed in the secondary ERM specimens compared to the idiopathic ERM specimens. Immunohistochemical analysis revealed GFAP-positive cells in 4 of the 11 idiopathic ERMs cases, yet no nestin-, Ki-67-, or CD34-positive cells in those cases. In contrast, there were 4 GFAP-positive cases, 2 Ki67-positive cases, 3 CD34-positive cases, and 7 cases including nestin-positive cells. The findings of this study indicate that there are different histological characteristics between idiopathic and secondary ERM and that mature nestin-positive cells in the retina might be related to secondary ERM formation. [ABSTRACT FROM AUTHOR]

The expression of versican, a hyaluronic acid (HA)-binding protein, during the development and differentiation of the retina has been reported. In this study, we performed histochemical and immunohistological analysis of HA and versican from the ciliary body to the retina in cynomolgus monkey eyes. Paraffin-embedded sections of cynomolgus monkey eyes, including from the ciliary body to the macular region, were prepared. The distribution of versican and HA was examined by histochemical and immunohistochemical methods. The sites of HA expression and versican expression in the eye specimens were similar. Expression of HA and versican was observed in the peripheral retina and ciliary body, but not from the macular region to the mid-periphery of the retina. Versican was strongly expressed in the ciliary body, particularly in the non-pigmented ciliary epithelium. Expression in the retina from the periphery to posterior pole gradually decreased. Versican is expressed from the ciliary body to the peripheral retina, but this expression decreases toward the posterior pole. This suggests a physiological function for versican in the peripheral retina. [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis (EoE) is diagnosed by microscopic findings of eosinophilic infiltration into the squamous epithelium. In contrast, another disease concept termed 'eosinophilic esophageal myositis (EoEM)' has been proposed, whereby there is eosinophilic infiltration into the muscularis propria instead. A 60-year-old man was referred to our hospital for chest pain, dysphagia, and several episodes of esophageal food impaction. Although EoE was suspected based on clinical features, biopsy specimens showed no mucosal eosinophilic infiltration. Endoscopic ultrasound (EUS) showed thickening of the muscularis propria layer and subsequent EUS-guided fine-needle aspiration biopsy (EUS-FNA) revealed eosinophilic infiltration into the muscularis propria. Although the patient's symptoms gradually improved after steroid administration, complete remission was not achieved after 1 year of treatment. This case may reflect a disorder distinct from typical EoE based on eosinophilic infiltration of the muscularis propria but not the squamous epithelium, and we, therefore, diagnosed it as EoEM using the EUS-FNA findings as reference. [ABSTRACT FROM AUTHOR]

The patient was a 42-year-old man who presented at our hospital with obstructive jaundice. Although antinuclear antibody test results were negative, and immunoglobulin G4 (IgG4) was not elevated, endoscopic ultrasound revealed a mixed internal hyperechoic and diffuse hypoechoic pattern, a finding consistent with autoimmune pancreatitis. Endoscopic retrograde cholangiopancreatography further revealed irregular narrowing of the main pancreatic duct and sclerosing cholangitis with distal biliary stricture. In addition, endoscopic ultrasound with fine needle aspiration cytology resulted in a diagnosis of type 1 autoimmune pancreatitis. Oral prednisolone treatment was initiated at 30 mg/day, and the dosage was gradually decreased. However, in accordance with the patient's wishes, maintenance treatment was discontinued once dosage reached 5 mg/day. Despite this, relapse of obstructive jaundice occurred 1 month post discontinuation, and was treated with methyl-prednisolone pulse therapy (500 mg/day) followed by oral prednisolone. However, computed tomography, magnetic resonance imaging, and endoscopic ultrasound did not reveal sufficient improvement after 6 months of treatment. Therefore, an immunosuppressant (azathioprine) was introduced. Subsequent imaging analyses and endoscopic ultrasound fine needle aspiration revealed clear improvements in pathology. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the clinical findings and original treatment method of granulation tissue formation post silicone intubation (SI) for primary acquired lacrimal drainage obstruction (PALDO). Methods: This retrospective, consecutive, comparative, interventional case series study involved 85 consecutive PALDO patients treated by SI and followed by dacryoendoscopy for 12 months post surgery. Patients in whom complication by granulation tissue formation occurred were treated every 2 weeks until it disappeared with an injection of prednisolone acetate ophthalmic ointment into the lacrimal duct without removing the tube. The frequency of granulation tissue formation post SI, relationship between the locations where the primary obstruction and granulation tissue formation occurred, and impact of the complication on the surgical outcome were evaluated. Results: Granulation tissue formation occurred in 9 of the 85 cases (10.6 %) at 2-8 weeks post surgery, yet disappeared via treatment during that same period. No relationship was found between the location of the primary obstruction and the granulation tissue formation, and no statistical difference was found when comparing the success rate of our surgical treatment in patients with or without the complication ( P = 0.46, Fisher's exact test). Conclusions: Complication by granulation tissue formation occurred in 10.6 % of the patients who underwent SI for PALDO, yet the injection of prednisolone acetate ophthalmic ointment into the lacrimal passage may have successfully treated the complication without removal of the silicone tube. [ABSTRACT FROM AUTHOR]

The purpose of this study was to report the surgical outcomes after creating a 120° intentional giant retinal tear for use in removing hemorrhage and subretinal proliferative tissue in patients with polypoidal choroidal vasculopathy (PCV) or age-related macular degeneration (ARMD). This study involved 12 eyes of 12 patients (10 eyes: PCV, 2 eyes: ARMD). After removal of the lens in phakic eyes, we performed a vitrectomy with artificial posterior vitreous detachment. Subsequently, a 120° intentional giant retinal tear was created in the temporal periphery, the retina was then turned, and the subretinal hemorrhage and proliferative tissue were removed. In order to preserve as much of the retinal pigment epithelium (RPE) as possible, we used a bimanual technique under direct visualization. After stretching the retina by use of perfluorocarbon liquid (PFCL), we performed endophotocoagulation around the tear followed by PFCL/silicone oil exchange. Except for 1 eye in which extensive loss of the RPE occurred, the fundus findings and the visual acuity (VA) improved in all patients. In addition, postoperative VA improved to ≥20/50 in 3 eyes in which the macular RPE was preserved. This surgical procedure is an effective treatment for PCV or ARMD patients with extensive subretinal hemorrhage and proliferative tissue. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of the postoperative administration of rebamipide ophthalmic suspension on the success rate of lacrimal stent intubation (LSI) for the treatment of primary acquired nasolacrimal duct obstruction (PANDO). Methods: This comparative interventional cohort study investigated 110 consecutive patients with PANDO who were treated with LSI and followed up for 12 months postoperatively at one institution. LSI was performed by one surgeon, and all patients received identical postoperative care. Among the total 110 patients, 71 underwent LSI with postoperative administration of rebamipide ophthalmic suspension, and 39 underwent LSI without administration of the suspension. Data related to patient age, gender, laterality, and postoperative administration of rebamipide ophthalmic suspension were collected and used as independent variables, and logistic regression analyses were performed to compare the anatomical success rate at 12 months postoperatively between patients with and without postoperative administration of the suspension. Results: The anatomical success rate of LSI in patients with and without postoperative administration of rebamipide ophthalmic suspension was 90.1 and 69.2 %, respectively. A comparison of these success rates showed statistical significance, in that the rate of treatment success was higher in PANDO patients who underwent LSI with postoperative administration of the suspension [odds ratio (OR), 3.37; P < 0.05]. Conclusions: The findings of this study show that postoperative administration of rebamipide ophthalmic suspension increases the rate of anatomical success in patients who undergo LSI for the treatment of PANDO. [ABSTRACT FROM AUTHOR]

Purpose: To study the indications for and effectiveness of Nunchaku-style silicone tube intubation (NSTI) in treating primary acquired lacrimal drainage obstruction (PALDO). Methods: In this interventional cohort study, 235 consecutive patients in 1 institution who had complete lacrimal obstruction were investigated. Of those, 212 PALDO patients were enrolled, and 156 of the PALDO patients ultimately satisfied our treatment protocol and were then followed up for 12 months postsurgery. Patients without dacryocystitis underwent NSTI, while those with dacryocystitis underwent NSTI or endonasal dacryocystorhinostomy (EN-DCR) using the NST as a stent. The tubes were left in place for 8 weeks, and all patients received identical postoperative care. Resolution was deemed as patency assessed by irrigation. Logistic regression analyses were performed to compare the success of NSTI for upper (puncta and canaliculus) and lower (lacrimal sac and nasolacrimal duct) obstruction, NSTI for lower obstruction with and without dacryocystitis, and NSTI and EN-DCR for lower obstruction with dacryocystitis. Results: Comparison of the success rates at 12 months postsurgery showed significance as follows: treatment with NSTI was more successful for upper obstruction (94.6 %) than for lower obstruction (71.4 %) [odds ratio (OR) 8.23; P < 0.01]; treatment with NSTI was more successful for lower obstruction without dacryocystitis (82.9 %) than for dacryocystitis (52.4 %) (OR 4.96; P < 0.05); and treatment with EN-DCR (95.5 %) was more successful than NSTI (52.4 %) for treating lower obstruction with dacryocystitis (OR 16.99; P < 0.001). Conclusions: NSTI is effective for treating PALDO; however, EN-DCR is more effective for treating PALDO cases complicated by dacryocystitis. [ABSTRACT FROM AUTHOR]

Purpose: To report a case of pseudo-unilateral occult macular dystrophy (OMD) with an Arg45Trp mutation in the RP1L1 gene and had unilateral functional changes for about 9 years. Case report: A 64-year-old woman with a decimal visual acuity of 1.0 in both eyes complained about difficulties with visual tasks because of presbyopia. At the age of 65 years, her visual acuity in the left eye decreased to 0.2, while that in the right eye was 0.7. The fundus of both eyes was normal except for drusen. After 10 years and at the age of 75 years, her visual acuity in the right eye decreased to 0.3. Focal macular electroretinograms (ERGs) at this time were severely attenuated in both eyes, while the full-field ERGs were within normal limits. Ophthalmoscopy showed that the fundus of both eyes was still normal. Genetic analysis revealed a heterozygous mutation, Arg45Trp, in the RP1L1 gene. Conclusions: These findings indicate that the phenotype in some cases of OMD with an Arg45Trp mutation in the RP1L1 gene can be unilateral for a considerable period. [ABSTRACT FROM AUTHOR]

The diagnosis of amyotrophic lateral sclerosis (ALS) is difficult due to lack of definitive biomarkers. Our aim was to identify characteristic serum protein patterns that could provide candidate biomarkers for ALS. We divided mutant superoxide dismutase-1 (SOD1) rats into three groups based on disease progression: pre-symptom (90 days), onset, and end-stage. After separation of serum proteins using two-dimensional electrophoresis, we selected clear protein spots and identified two candidate proteins-inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) and glutathione peroxidase 3 (Gpx3). The 120 kDa ITIH4 increased at the onset of the disease and the 85 kDa ITIH4, a cleaved form, at the end-stage in the sera of the SOD1 rats. Expression of the 85 kDa ITIH4 was substantial in ALS compared with controls or patients with muscular dystrophy, Alzheimer diseases, or Parkinson diseases. The Gpx3 protein levels in the sera of SOD1 rats were upregulated pre-symptom and gradually decreased as the disease progressed. The Gpx3 protein levels were lower in the sera of the patients with ALS than in other diseases. These results indicate that ITIH4 and Gpx3 are potential biomarkers for ALS. [ABSTRACT FROM AUTHOR]

Background: We have developed inorganically-coated all-trans retinoic acid (atRA) nanoparticles, nano-sized egg-like particles of atRA (NANOEGG®-atRA). The purpose of this study was to determine the effects of NANOEGG®-atRA on corneal wound healing in vivo and in vitro. Methods: A rabbit corneal epithelial wound healing model was exposed to different concentrations of NANOEGG®-atRA. Wound healing was serially quantified as the ratio of fluorescein-stained area at the selected times to that at baseline. After wound closure, the barrier function of the cornea was determined using low concentrations of tropicamide. At the completion of the experiments, the corneal epithelium was histologically examined. For the in vitro studies, linear scratch wounds were made on cultured SV40-immortalized human corneal epithelial cells (HCE-T). Then, the cells were exposed to different concentrations of NANOEGG®-atRA, and wound healing was determined by the degree of closure of the scratch wound. In addition, the effects of NANOEGG®-atRA on the proliferation of HCE-T cells were determined by WST-8 assays. Results: Exposure to NANOEGG®-atRA decreased the injured area 24 hrs after the ablation. The maximum effect of NANOEGG®-atRA was observed at a concentration of 33 mM. Histologically, no abnormal or differentiated corneal epithelial cells were observed in the histological sections treated with NANOEGG®-atRA. The tropicamide-induced pupillary dilation was significantly slowed in the eyes treated with NANOEGG®-atRA. NANOEGG®-atRA at concentrations of 3.3 and 33 nM induced earlier wound closure in vitro, but did not induce proliferation of HCE-T cells. Conclusion: NANOEGG®-atRA promotes wound healing and should be considered for the treatment of wounds of the corneal epithelium. [ABSTRACT FROM AUTHOR]

Modulation of enzyme activity through nitrosylation has recently been identified as a new physiological activity of nitric oxide (NO). We hypothesized that NO enhances the TNF-α-induced death of retinal neurons through a suppression of nuclear factor-κB (NF-κB) by nitrosylation. In this study, cells from the RGC-5 line were exposed to different concentrations (2.0, 10, and 50 ng/ml) of TNF-α, and the degree of TNF-α-induced cell death was determined by the WST-8 assay and by flow cytometric measurements of the externalization of phosphatidylserine. The effects of etanercept, a soluble TNFR-Fc fusion protein, and S-nitroso- N-penicillamine (SNAP), an NO donor, on the toxicity were determined. Experiments were also performed to determine whether nitric oxide synthase (NOS) was associated with the toxicity of TNF-α. The activation of NF-κB was determined by the detection of the p65 subunit in the nuclear extracts. Our results showed that exposure of RGC-5 cells to different concentrations of TNF-α significantly decreased the number of living cells in a dose-dependent way. The death was partially due to apoptosis with an externalization of phosphatidylserine, and the death was suppressed by etanercept. Exposure to TNF-α increased the activation of NF-κB and the expression of iNOS. Although NF-κB inhibitors suppressed the increase of iNOS, they also potentiated the TNF-α-induced death. Both L-NAME and aminoguanidine, both NOS inhibitors, rescued the cells from death. In contrast, addition of SNAP caused nitrosylation of the inhibitory κB kinase, and suppressed the NF-κB activation and potentiated the TNF-α-induced neurotoxicity. These results indicate that NO potentiates the neurotoxicity of TNF-α by suppressing NF-κB. [ABSTRACT FROM AUTHOR]

Objectives: This study evaluates the feasibility of chemosensitivity testing by use of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) samples and determines the optimum cut-off value for gemcitabine. Methods: Thirty-four consecutive patients with unresectable pancreatic cancer were enrolled. Chemosensitivity (treated/control ratio: T/C ratio) was calculated as the quantity of adenosine triphosphate for a tumor treated with gemcitabine as a percentage of that for the control. To identify the cut-off value sufficient to predict 180 days of progression-free survival (PFS), the receiver operating characteristic curve and the corresponding area under the curve (AUC) were calculated. Results: The success of this assay was 88.2% (30/34); therefore, 30 patients were assessable and included in the population of analyzable patients.. The response was 6.7%. Median PFS was 96 days and median overall survival was 241 days, respectively. The cut-off value was determined as 74% (AUC, 0.745; p = 0.053; 95% CI 0.485-1.005). According to this cut-off value, we predicted 180 days PFS with a sensitivity and specificity of 71.4 and 91.3%, respectively. When patients were divided into two groups at T/C ratio 74%, a significant difference was found in PFS (median 77 vs. 205 days, p = 0.0036). Moreover, T/C ratio < 74% and decrease of CA19-9 were significant and independent prognostic factors by multivariate analysis. Conclusion: Chemosensitivity testing by use of EUS-FNA samples in patients with unresectable pancreatic cancer is feasible. This definition emphasizes the possibility of selecting patients for whom favorable results from gemcitabine treatment can be expected. [ABSTRACT FROM AUTHOR]

A 58-year-old woman was admitted to our institute in June 2007 because of obstructive jaundice. A mass in the pancreatic head and multiple swollen lymph nodes surrounding the common hepatic artery were identified using computed tomography (CT). Subsequently, endoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS-FNA) was done. Histopathologic results revealed anaplastic carcinoma of the pancreas. Using specimens obtained with EUS-FNA, chemosensitivity testing with adenosine triphosphate assay was performed. Testing indicated high chemosensitivity to paclitaxel (PTX). According to this result, chemotherapy using PTX was performed, and the primary lesion and lymph node metastases disappeared completely on CT. The patient has been doing well with no recurrence for 1 year and 11 months since initial chemotherapy. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) with rapid on-site evaluation (ROSE) has been reported to provide a more accurate diagnosis than EUS-FNA without such evaluation. However, even endosonographers can evaluate ROSE regarding sample adequacy. The aim of this study was to evaluate the diagnostic accuracy of EUS-FNA with ROSE by endosonographers compared to ROSE by cytopathologists in patients with solid pancreatic masses. Between September 2001 and October 2005, of the 73 EUS-FNA procedures with the final diagnoses, 38 procedures after the introduction of ROSE by endosonographers (September 2001–September 2003, period 1), and 35 procedures after the introduction of ROSE by cytopathologists (October 2003–October 2005, period 2) were included. The specimens were stained with Diff-Quik stain and assessed. When the on-site assessors (endosonographers or cytopathologists) indicated that the amounts of cell samples were adequate, the procedure was stopped. Results are presented with 95% confidence limits. The average numbers of needle passes were 4.0 ± 1.6 and 3.4 ± 1.5 in periods 1 and 2, respectively ( P = 0.06). The specimen collection rates were 97.4 and 97.1% in periods 1 and 2, respectively ( P = 0.51). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for malignancy and benign were 92.9, 100, 100, 83.3, and 94.7%, respectively, in period 1, and 93.1, 100, 100, 75.0, and 94.3%, respectively, in period 2 ( P = 0.97, P = 1.0, P = 1.0, P = 0.65, P = 0.93, respectively). No complications were seen. For accurate diagnosis, ROSE should be performed during EUS-FNA by the endosonographer, if no cytopathologist is available. [ABSTRACT FROM AUTHOR]

The original publication of this paper contains mistakes. [ABSTRACT FROM AUTHOR]

This study was designed to detect apoptosis in both human senile cataracts and cataracts associated with diabetic retinopathy (DR) and to elucidate the signaling pathway involved in its regulation. Samples of human cataracts were obtained from 56 patients (senile cataracts, n = 40; cataracts with DR, n = 16) and were analyzed by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method, transmission electron microscopy, immunohistochemistry, and reverse transcriptase-polymerase chain reaction (RT-PCR) assay of apoptotic modulators. The TUNEL study demonstrated that the percentage of TUNEL-positive cells in the cataracts with proliferative DR was higher than in the senile cataracts ( P < 0.05). The immunohistochemistry and RT-PCR assay showed a higher level of Fas expression and Fas mRNA in the cataracts with DR than in the senile cataracts, although there was no difference in the expression level of the Fas ligand, Bcl-2, and their mRNAs between both groups. The number of dark cells, which were characterized by a convoluted nucleus and chromatin condensation with abundant free 3′-OH DNA ends, was higher in the cataracts with DR than in the senile cataracts ( P < 0.01). Apoptosis plays an important role in the development of cataracts with DR, but not in senile cataracts, and may be induced by Fas-mediated signaling. [ABSTRACT FROM AUTHOR]

Purpose. To investigate the changes in retinal blood flow (RBF) during a 75-g oral glucose tolerance test in the contralateral eye of patients with retinal branch vein occlusion (BRVO). Methods. Seventeen patients with BRVO were included. None had a known history of diabetes mellitus. The blood velocity and vessel diameter of the upper temporal retinal artery in the contralateral eye were measured using laser Doppler velocimetry with an eye-tracking system before and 1, 2, and 3 h after oral intake of 75 g glucose. Blood sugar, systemic blood pressure, and intraocular pressure were monitored. Eleven healthy volunteers were examined similarly as control. Results. Nine patients (53%) with BRVO had an abnormal pattern on the glucose tolerance test. RBF significantly increased at 1, 2, and 3 h in eight patients with normal glucose tolerance. The changes in RBF primarily resulted from changes in vessel diameter; the blood velocity did not change significantly. The nine patients with impaired glucose tolerance or diabetes mellitus had a RBF pattern that was significantly lower at 2 and 3 h than those with normal oral glucose tolerance. In the control group, all 11 volunteers showed the same increases in RBF at 2 and 3 h as the BRVO patients with a normal glucose pattern. Conclusion. A relatively high number of patients with BRVO had an abnormal pattern on glucose tolerance testing. Glucose intake increased RBF in BRVO patients without diabetes and in healthy volunteers. The RBF response may differ between subjects with diabetes and those without diabetes. [ABSTRACT FROM AUTHOR]

• Background: Diplopia after cataract surgery has been reported by several authors, but diplopia after recovery from vitreous hemorrhage (VH) has not been described. •Methods: We examined eight patients with manifest exotropia and binocular diplopia after recovery from dense VH by vitreous surgery. VH was bilateral in three patients and unilateral in five, and lasted for an average of 7.7 years. • Results: Visual acuity before vitrectomy ranged from 20/200 to light perception; that after vitrectomy ranged from 20/20 to 20/60. Exotropia was present in all patients after vitrectomy. Additionally, seven out of eight patients had vertical strabismus with an average deviation of 6 prism diopters (Δ). Fusion was confirmed in four patients with an average amplitude of 13 Δ. Four patients underwent horizontal strabismus surgery. Fusion was present in two before strabismus surgery and in all four after surgery; however, unstable diplopia persisted in three of the four after surgery. • Conclusion: Diplopia after vitrectomy for longstanding VH may occur due to fusion impairment comparable to that occasionally seen after surgery for traumatic cataract. [ABSTRACT FROM AUTHOR]

This study aimed to clarify predictive biomarkers of mild and severe ocular complications of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) by examining the cytokines in tears. In 121 chronic-phase SJS/TEN eyes, cytokines in tear samples collected using Schirmer test strips were measured, and ocular sequelae severity was evaluated using an Ocular Surface Grading Score (OSGS) involving 7 components (conjunctivalization, neovascularization, opacification, keratinization, symblepharon, and upper/lower conjunctival-sac shortening), with findings categorized into grades 0–3 (maximum total OSGS: 21). Changes in cytokines between the mild and severe groups (mild: total OSGS of 10 or less, severe: total OSGS of 11 or more), and changes between SJS/TEN cases with and without each of the 7 components, were compared. In the severe group, there was significant upregulation of interleukin (IL)-8 (P < 0.01) and Granzyme B (GrzB) (P < 0.05). IL-8 was significantly upregulated in eyes with conjunctivalization, neovascularization, or opacification, GrzB was upregulated in eyes with keratinization, interferon-γ-inducible protein 10 (IP-10) was downregulated in eyes with conjunctivalization or neovascularization, and IL-1α was upregulated in eyes with opacification (all: P < 0.05). IL-8 and IP-10 was involved in conjunctivalization and neovascularization, while GrzB was involved in keratinization. IL-8 and GrzB in tears may reflect SJS/TEN-related ocular sequelae severity. [ABSTRACT FROM AUTHOR]

The fovea centralis, an anatomically concave pit located at the center of the macula, is avascular, hypoxic, and characteristic of stem-cell niches of other tissues. We hypothesized that in the fovea, undifferentiated retinal-stem-cell-like cells may exist, and that neurogenesis may occur. Hence, we performed an immunohistological study using cynomolgus monkey retinas. After preparing frozen tissue sections of the retina including the foveal pit, immunostaining was performed for glial fibrillary acidic protein (GFAP), nestin, vimentin, neuron-specific class III β-tubulin (Tuj-1), arrestin 4, neurofilament, CD117, CD44, Ki67, and cellular retinaldehyde-binding protein (CRALBP), followed by fluorescence and/or confocal microscopy examinations. Immunostaining of the tissue sections enabled clear observation of strongly GFAP-positive cells that corresponded to the inner-half layer of the foveolar Müller cell cone. The surface layer of the foveal slope was partially costained with GFAP and vimentin. Tuj-1-positive cells were observed in the innermost layer of the foveolar retina, which spanned to the surrounding ganglion cell layer. Moreover, colocalization of Tuj-1 and GFAP was observed at the foveal pit. The coexpression of CD117 and CD44 was found in the interphotoreceptor matrix of the fovea. The foveolar cone stained positive for both nestin and arrestin 4, however, the photoreceptor layer outside of the foveola displayed weak staining for nestin. Colocalization of nestin and vimentin was observed in the inner half of the Henle layer, while colocalization of nestin and neurofilament was observed in the outer half, predominantly. Scattered Ki67-positive cells were observed in the cellular processes of the outer plexiform layer and the ganglion cell layer around the foveola. Immunostaining for CRALBP was negative in most parts of the GFAP-positive area. The Müller cell cone was divided into GFAP-strongly positive cells, presumably astrocytes, in the inner layer and nestin-positive/GFAP-weakly positive radial glia-like cells in the outer layer. These findings indicated that groups of such undifferentiated cells in the foveola might be involved in maintaining morphology and regeneration. [ABSTRACT FROM AUTHOR]