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Body temperature in homeothermic animals does not remain constant but displays a regular circadian fluctuation within a physiological range (e.g., 35°C–38.5°C in mice), constituting a fundamental systemic signal to harmonize circadian clock-regulated physiology. Here, we find the minimal upstream open reading frame (uORF) encoded by the 5′ UTR of the mammalian core clock gene Per2 and reveal its role as a regulatory module for temperature-dependent circadian clock entrainment. A temperature shift within the physiological range does not affect transcription but instead increases translation of Per2 through its minimal uORF. Genetic ablation of the Per2 minimal uORF and inhibition of phosphoinositide-3-kinase, lying upstream of temperature-dependent Per2 protein synthesis, perturb the entrainment of cells to simulated body temperature cycles. At the organismal level, Per2 minimal uORF mutant skin shows delayed wound healing, indicating that uORF-mediated Per2 modulation is crucial for optimal tissue homeostasis. Combined with transcriptional regulation, Per2 minimal uORF-mediated translation may enhance the fitness of circadian physiology., 全身の体内リズムを調和させるRNA配列の発見 --体温の日内変化に合わせてしなやかに調和させる--. 京都大学プレスリリース. 2023-03-07.

We report the variability in carbon and oxygen isotopic compositions, chemical compositions, and cathodoluminescence intensities within calcite grains in the Yamato-791198 CM chondrite measured by secondary ion mass spectrometry. To understand the change in carbon isotopic compositions during calcite formation, the carbon isotope-analyses were performed on a series of crystal growth bands of each calcite grain. The crystal growth of calcite grains was inferred from comprehensive analyses of oxygen isotopes, chemical compositions, and cathodoluminescence characteristics. The observed δ18O variations within individual grains are as large as 13‰. The oxygen-isotope data plot on a single straight line with a slope of 0.61 ± 0.06 (2σ) in an oxygen three-isotope diagram. This slope steeper than that of the terrestrial fractionation line indicates that the oxygen isotopic compositions of aqueous fluids evolved from higher δ18O and Δ17O to lower δ18O and Δ17O compositions due to the oxygen-isotope exchange between water and anhydrous silicates in the parent body. Thus, calcite crystals grew from higher Δ17O to lower Δ17O areas. The crystal growth inferred from oxygen isotopic compositions is corroborated by the morphology and cathodoluminescence characteristics of the calcite grains. The minor element concentrations of the calcite grains did not increase/decrease monotonically during calcite formation. The δ13C variations within individual grains are no more than 4‰ except for one grain. The intra-grain δ13C variations observed here are much smaller than inter-grain δ13C variations of ∼80‰ previously reported. These observations indicate that the carbon isotopic compositions of dissolved carbon species did not change during calcite formation and that they were locally heterogeneous which reflects variable proportions of carbon reservoirs with different isotopic compositions.

Liver cancer, including hepatocellular carcinoma (HCC), is the fifth most common cause of cancer deaths in Japan. The main treatment options for HCC are surgical resection, liver transplantation, radiofrequency ablation (RFA), transarterial chemoembolization (TACE), and systemic chemotherapy. Here, recent medical treatments for HCC, including surgery, percutaneous ablation, transcatheter arterial chemoembolization/transcatheter arterial embolization, and drug therapy, are reviewed with a focus on Japan.

Simple hepatic cysts are typically saccular, thin-walled masses with fluid-filled epithelial lined cavities that arise from aberrant bile duct cells during embryonic development. With the development of diagnostic modalities such as ultrasonography, computed tomography and magnetic resonance imaging, simple hepatic cysts are seen with relative frequency in daily clinical examination. US is the most useful and noninvasive tool for the diagnosis of simple hepatic cysts, and can generally differentiate simple hepatic cysts from abscesses, hemangiomas and malignancies. Cysts with irregular walls, septations, calcifications or daughter cysts on US should be evaluated with enhanced CT or MRI to differentiate simple hepatic cysts from cystic neoplasms or hydatid cysts.Growth and compression of hepatic cysts cause abdominal discomfort, pain, distension and dietary symptoms such as nausea, vomiting, a feeling of fullness and early satiety. Complications of simple hepatic cysts include infection, spontaneous hemorrhage, rupture, and external compression of biliary tree or major vessels.Asymptomatic simple hepatic cysts should be observed. Treatment for symptomatic simple hepatic cysts includes percutaneous aspiration, aspiration followed by sclerotherapy, and surgery. The American College of Gastroenterology clinical guidelines recommend laparoscopic fenestration based on its high success rate and low invasiveness. Percutaneous procedures for treatment of simple hepatic cysts are particularly effective for the immediate palliation of patient symptoms; however, they are not generally recommended because of the high rate of recurrence.Management of simple hepatic cysts requires correct differentiation from neoplasms and infections, and the selection of a reliable treatment.

Background The number of patients with hemodialysis is increasing increased yearly. Few reports are available on hepatobiliary and gastrointestinal surgery in these patients. Patients and methods A total of 222 patients who underwent partial liver resection or segmentectomy in our hospital between January 2015 and September 2019 were included in this study. Patients were divided into the hemodialysis group (n=9) and non-hemodialysis group (n=213). Results No significant difference was observed in postoperative complications between the hemodialysis and non-hemodialysis group. The hemodialysis group had a significantly higher infectious complication rates than the non-hemodialysis group (33.3% vs. 8.0%, p=0.009). In logistic regression analysis, hemodialysis was only a significant risk factor for postoperative infectious complications (OR=5.61, 95% CI=1.12-28.20, p=0.036). Conclusion Liver resections, at least segmentectomy or smaller, is acceptable in patients on hemodialysis. However, these patients may have a higher risk of postoperative infectious complications than other patients.

Background Patients with recurrent hepatocellular carcinoma or metastatic liver cancer from colorectal cancer after surgical resection have traditionally been treated with conventional open surgery. However, recent technical advances have facilitated laparoscopic repeat hepatectomy (LapRH), which has advantages over open laparotomy. We describe the results of LapRH at our institution and retrospectively compare short-term outcomes after LapRH and initial laparoscopic partial liver resection (LapPLR). Methods From April 2010 through December 2017, 24 patients (16 men, 8 women; median age, 69 years) underwent LRH for cancer recurrence or metastasis after initial partial hepatectomy at our institution. LapRH involved partial hepatectomy in 21 patients and lateral segmentectomy in 3 patients. Short-term outcomes (operative time, intraoperative blood loss, and postoperative hospital stay) for these 24 patients were compared with those for 117 patients who underwent initial LapPLR during the same period. Results There were no significant differences between the LapPLR and LapRH groups in baseline characteristics, including patient age and underlying disease. No LapRH procedure required conversion to open surgery. There were no statistically significant differences between the groups in median operation time (268 min for LapPLR, 294 min for LapRH; p = 0.55), blood loss (224.0 mL for LapPLR, 77.5 mL for LapRH; p = 0.76), or length of hospital stay (11.0 days for LapPLR, 10.2 days for LapRH; p = 0.83). Conclusions LapRH for recurrent liver cancer yielded satisfactory outcomes when compared with those of initial hepatectomy. Further studies are needed, however, to confirm the present results.

Ravuconazole is a fourth generation azole exerting strong antifungal activity, with low drug-drug interaction and hepatic dysfunction risks. Fosravuconazole l-lysine ethanolate (fosravuconazole; NAILIN® Capsules 100 mg) was developed as a ravuconazole prodrug. Ravuconazole exerts strong antifungal activity against various pathogenic fungi including dermatophytes and Candida. Through prodrug formation, pharmacokinetic improvement was achieved, and bioavailability after oral administration reached 100%. The plasma ravuconazole concentration became 10-35 times higher than with current oral anti-onychomycosis drugs, and showed good skin and nail tissue transition plus tissue retention. This improvement obtained with fosravuconazole reflects its superior pharmacokinetic properties. We conducted a clinical trial with fosravuconazole orally administered once a day (100 mg ravuconazole) for 12 weeks in Japanese onychomycosis patients. The ravuconazole concentration in nail tissues exceeded the MIC90 against dermatophytes, even after treatment completion. Furthermore, the placebo-controlled, double-blind, comparative trial showed significantly superior effects (at 48 weeks after starting treatment, with a complete cure rate of 59.4%, a marked clinical improvement rate of 83.1%, and a mycological cure rate by direct microscopy of 82.0%). The major adverse reactions were laboratory abnormalities and gastrointestinal disorders with no severe symptoms, suggesting good tolerability. Fosravuconazole has fewer drug-drug interactions, is not affected by food, and is also expected to improve medication adherence since the administration period is only 12 weeks and there is no drug-free period as required with pulse therapy. Thus, fosravuconazole has many favorable pharmacological properties and can reasonably be expected to become a new oral treatment option for onychomycosis.

Follicular pancreatitis (FP) is characterized by nodular mass composed of lymphoid hyperplasia and fibrosis. We here present radiological and pathological features of three cases of FP. The three patients were middle- or old-aged men, and nodular mass was pointed out at health examination. Computed tomography failed to demonstrate a mass. Magnetic resonance imaging demonstrated a mass in each case. 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET) demonstrated two nodular masses with high standardized uptake value (SUV) in two cases and single mass in one case. The pathological examination disclosed two lesions with fibrosis and hyperplastic lymphoid follicles in two cases and one lesion in one case. Masses with high SUV appeared to correspond with the lesions of FP. Compared with the features of FDG-PET images of pancreatic ductal carcinoma, multiple lesions with high SUV favor a diagnosis of FP rather than pancreatic cancer. FDG-PET is useful for the diagnosis of FP.

The Pringle maneuver is often used in liver surgery to minimize bleeding during liver transection. Many authors have demonstrated that intermittent use of the Pringle maneuver is safe and effective when performed appropriately. However, some studies have reported that the Pringle maneuver is a significant risk factor for portal vein thrombosis. In this study, we evaluated the effectiveness of portal vein flow after the Pringle maneuver and the impact that massaging the hepatoduodenal ligament after the Pringle maneuver has on portal vein flow. Patients treated with the Pringle maneuver for hepatectomies performed to treat hepatic disease at our hospital between August 2014 and March 2019 were included in the study (N = 101). We divided these patients into two groups, a massage group and nonmassage group. We measured portal vein blood flow with ultrasonography before and after clamping of the hepatoduodenal ligament. We also evaluated laboratory data after the hepatectomy. Portal vein flow was significantly lower after the Pringle maneuver than before clamping of the hepatoduodenal ligament. The portal vein flow after the Pringle maneuver was improved following massage of the hepatoduodenal ligament. After hepatectomy, serum prothrombin time was significantly higher and serum C-reactive protein was significantly lower in the massage group than in the nonmassage group. Massaging the hepatoduodenal ligament after the Pringle maneuver is recommended in order to quickly recover portal vein flow during hepatectomy and to improve coagulability.

Background: Relatively high mortality and morbidity rates are reported after liver resection (LR). However, the early predictors of complications after LR are not clear. This study was performed to clarify the usefulness of procalcitonin (PCT) for the early prediction of complications after elective LR. Methods: This observational study included 72 consecutive patients who underwent elective LR from December 2015 to March 2017. Patients were categorized into two groups: those with and without postoperative complications (Clavien-Dindo grade ≥II). The values of postoperative inflammatory markers (white blood cell [WBC] count, C-reactive protein [CRP] and PCT) were compared between the two groups. Results: CRP and PCT were significantly higher in patients with than without complications; however, the WBC count showed no difference within 5 days postoperatively. The maximum area under the receiver operating characteristic curves within 2 days after LR using the WBC count, CRP and PCT were 0.608, 0.697 and 0.860, respectively, PCT had the best predictive ability in the early postoperative period. The PCT level peaked within 2 days postoperatively in 61 patients (85%). The maximum PCT level within 2 days postoperatively (PCT1−2) was significantly higher in patients with than without complications (0.52 vs. 0.19 ng/mL, p1−2 level of 0.35 ng/mL achieved 80% sensitivity and 83% specificity. In patients without complications, there was no difference in PCT1−2 even when the surgical procedure differed (p=0.935). Conclusions: PCT1−2 is an early predictive marker after LR and can be similarly used regardless of the LR procedure.

Congenital biliary dilatation (CBD) is a congenital malformation involving both dilatation of the extrahepatic bile duct and pancreaticobiliary maljunction. Persistent reflux of pancreatic juice injures the biliary tract mucosa, resulting in chronic inflammation and higher rates of carcinogenesis in the biliary tract, including the gallbladder. Telomeres are repetitive DNA sequences located at the ends of chromosomes. Chromosomal instability due to telomere dysfunction plays an important role in the carcinogenesis of many organs. This study was performed to determine whether excessive shortening of telomeres occurs in the gallbladder mucosa of patients with CBD.Resected gallbladders were obtained from 17 patients with CBD, ten patients with cholecystolithiasis without pancreatic juice reflux, and 17 patients with normal gallbladders (controls) (median age of each group of patients: 37, 50, and 53 years, respectively). The telomere lengths of the gallbladder epithelium were measured by quantitative fluorescence in situ hybridization using tissue sections, and the normalized telomere-to-centromere ratio (NTCR) was calculated.The NTCRs in the CBD, cholecystolithiasis, and control groups were 1.24 [interquartile range (IQR) 1.125-1.52], 1.96 (IQR 1.56-2.295), and 1.77 (IQR 1.48-2.53), respectively. The NTCR in the CBD group was significantly smaller than that in the cholecystolithiasis and control groups (p = 0.003 and 0.004, respectively), even in young patients.Our findings indicate that telomere shortening in the gallbladder mucosa plays an important role in the process of carcinogenesis in patients with CBD. These results support the recommendation of established guidelines for prophylactic surgery in patients with CBD because CBD is a premalignant condition with excessive telomere shortening.

Delamination toughness of a mullite/Si/(SiC/SiC) environmental barrier coating (EBC) system has been measured using a shear-loading test. The EBC system is initially heated to a temperature of 1470 °C (above the melting point of Si (1414 °C)), and then repeated thermal exposure is carried out at a temperature 1320 °C (below the melting point of Si) for 2 h/cycle. Change of the delamination toughness with heat exposure is successfully obtained using the shear-loading test. Formation of cristobalite and transformation from α ↔ β during thermal cycling cause an increase of crack density in the Si bond coat layer and a resulting reduction in delamination toughness.

A simple technique for measurement of delamination toughness in environmental barrier coatings (EBCs) under shear loading has been developed. The technique overcomes micro damage accumulation properties of CMC substrate and a delamination toughness with a phase angle of ~ 80° could be obtained using a simple fixture. Demonstration of the present procedure is carried out using a BSAS/mullite + BSAS/Si standard EBC layer on a three-dimensional woven fabric SiC/SiC composite substrate. The delamination path suggests that it is possible to apply the method to wavy EBC coatings and also to thermal barrier coatings.

The indocyanine green (ICG) fluorescence method is reportedly useful for intraoperative visualization of hepatocellular carcinoma and metastatic liver cancer. Herein, we report the use of an ICG fluorescence navigation system for laparoscopic hepatectomy. The patient was a 73-year-old man with a surgical history of two laparotomies for hepatocellular carcinoma resection. During follow-up at our hospital, abdominal computed tomography revealed recurrence of hepatocellular carcinoma in the lateral area of the liver, after which the patient was hospitalized for surgery. His surgical history indicated that adhesions in the abdominal cavity were likely. We scheduled laparoscopic repeat hepatectomy (LRH) with an ICG fluorescence method in which ICG dye was injected intravenously 2 days before surgery. ICG fluorescence was easily detected intraoperatively. The advantages of the present approach are that it induces pneumoperitoneum and, with laparoscopic magnification, enables good visualization of the surgical field for LRH and clear intraoperative identification of the tumor, thus facilitating LRH. Laparoscopic partial resection of the liver (S3) was successfully performed; the operation time was 197 minutes and bleeding volume was 30 mL. Postoperative course was uneventful and he was discharged on postoperative day 10.

Ravuconazole is a fourth generation azole exerting strong antifungal activity, with low drug-drug interaction and hepatic dysfunction risks. Fosravuconazole l-lysine ethanolate (fosravuconazole; NAILIN

We previously demonstrated that rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), protects against N-methyl-D-aspartic acid (NMDA)-induced retinal neurotoxicity, but the mechanism underlying this protection is not fully understood. The present study aimed to examine the effects of everolimus, another inhibitor of mTOR, on neuronal cell loss and inflammation in a rat model of NMDA-induced retinal neurotoxicity, and to determine whether the extracellular signal-regulated kinase (ERK) pathway contributes to the protective effect of everolimus. Intravitreal injection of NMDA (200 nmol) resulted in (1) cell loss in the ganglion cell layer, (2) increase in the numbers of CD45-positive leukocytes and Iba1-positive microglia, and (3) phosphorylation of ribosomal protein S6 (pS6), a downstream indicator of mTOR activity. Simultaneous injection of everolimus with NMDA significantly attenuated these NMDA-induced responses. The neuroprotective effect of everolimus was almost completely prevented by the mitogen-activated protein kinase/ERK kinase inhibitor U0126 (1 nmol). NMDA increased the level of phosphorylated ERK (pERK) in Muller cells, and increase in pERK levels was also observed after co-injection of NMDA and everolimus. These results suggest that everolimus has a neuroprotective effect against NMDA-induced retinal neurotoxicity, an effect that seems to be mediated partly by activation of the ERK pathway in Muller cells.

Brain metastases originating from esophageal or gastric cancer are rare, accounting for 2.1-3.3% of all brain tumors registered in Japan. There are no established therapeutic measures for brain metastases, which accordingly have a poor prognosis. We present here a patient who survived for 5 years after surgery and gamma knife treatment of a cerebellar metastasis from esophagogastric adenocarcinoma. The primary gastric cancer was treated by laparotomy with total gastrectomy, splenectomy, and D2 lymphadenectomy. It was diagnosed as a esophagogastric junction Siewert type II tumor, type 3, tub1-2, pT3 (SS), pN1, and stage IIB on histopathological examination of the surgical specimen. Five months postoperatively, a solitary cerebellar metastasis was identified and surgically removed, followed by 20 Gy administered by gamma knife stereotactic radiosurgery; the patient received no subsequent treatment such as chemotherapy. Five years after the primary surgery, there have been no recurrences and the patient has a good quality of life. There are very few case reports of long-term survival after surgical treatment of cerebellar metastases from esophagogastric junction cancer. We report our experience and review published case reports of surgical treatment of brain metastases from gastric cancer.

Background The vein that runs between ventral and dorsal Segment 8 is called the anterior fissure vein (AFV). AFV is sometimes needed as a boundary for Subsegmentectomy in Segment 8. The aim of the present study was to investigate the AFV to determine whether the AFV can be used a landmark for subsegmentectomy of the liver at Segment 8. Methods We analyzed data from 151 patients who had undergone abdominal computed tomographic (CT) examinations. The position of the AFV is identified by determining whether the AFV drains flows into the proximal, medial, or distal portion of the middle hepatic vein (MHV) or right hepatic vein (RHV). Furthermore, the proximal region is divided into 2 halves; the proximal portion is designated as P1 and the distal portion is designated as P2. Results The AFV could be identified in 78.8% (119/151) of the patients. The AFV flowed into the MHV in 84.9% of the patients and into the RHV in 15.1%. Among the former, the AFV flowed into the proximal MHV in 69.7% of the patients. Conclusions Although the AFV might not be easily identifiable, the AVF can be used to determine the border between the ventral and dorsal portions of Segment 8. The AFV should thus be used as a landmark for Subsegmentectomy.

In the original publication of this article, Fig. 5 was published with incorrect color of the approximate lines of CBD and Control.

We previously demonstrated that rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), protects against N-methyl-D-aspartic acid (NMDA)-induced retinal neurotoxicity, but the mechanism underlying this protection is not fully understood. The present study aimed to examine the effects of everolimus, another inhibitor of mTOR, on neuronal cell loss and inflammation in a rat model of NMDA-induced retinal neurotoxicity, and to determine whether the extracellular signal-regulated kinase (ERK) pathway contributes to the protective effect of everolimus. Intravitreal injection of NMDA (200 nmol) resulted in (1) cell loss in the ganglion cell layer, (2) increase in the numbers of CD45-positive leukocytes and Iba1-positive microglia, and (3) phosphorylation of ribosomal protein S6 (pS6), a downstream indicator of mTOR activity. Simultaneous injection of everolimus with NMDA significantly attenuated these NMDA-induced responses. The neuroprotective effect of everolimus was almost completely prevented by the mitogen-activated protein kinase/ERK kinase inhibitor U0126 (1 nmol). NMDA increased the level of phosphorylated ERK (pERK) in Müller cells, and increase in pERK levels was also observed after co-injection of NMDA and everolimus. These results suggest that everolimus has a neuroprotective effect against NMDA-induced retinal neurotoxicity, an effect that seems to be mediated partly by activation of the ERK pathway in Müller cells.

We previously demonstrated that rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), protects against N-methyl-d-aspartic acid (NMDA)-induced retinal damage in rats. Rapamycin inhibits mTOR activity, thereby preventing the phosphorylation of ribosomal protein S6, which is a downstream target of S6 kinase. Therefore, we aimed to determine whether PF-4708671, an inhibitor of S6 kinase, protects against NMDA-induced retinal injury. Intravitreal injection of NMDA (200 nmol/eye) caused cell loss in the ganglion cell layer and neuroinflammatory responses, such as an increase in the number of CD45-positive leukocytes and Iba1-positive microglia. Surprisingly, simultaneous injection of PF-4708671 (50 nmol/eye) with NMDA significantly attenuated these responses without affecting phosphorylated S6 levels. These results suggest that PF-4708671 and rapamycin likely protect against NMDA-induced retinal damage via distinct pathways. The neuroprotective effect of PF-4708671 is unlikely to be associated with inhibition of the S6 kinase, even though PF-4708671 is reported to be a S6 kinase inhibitor.

Background: Nausea and vomiting are the most frequent side effects of opioids and may cause the opioids to be discontinued. New methods for preventing opioid-induced nausea can improve cancer pain management. Oxycodone is one of the most frequently used opioid used in Japan because patients receiving oxycodone report less nausea and vomiting than do patients receiving morphine. The reported incidence of oxycodone-induced nausea varies widely, although the true incidence remains unclear. As a first step toward preventing oxycodone-induced nausea, we aimed to determine the incidence of and risk factors for oxycodone-induced nausea and vomiting. Methods: In this observational study, we analyzed a series of consecutive inpatients with cancer who received oxycodone with prochlorperazine as a preventive antiemetic agent. Oxycodone (5 mg) was administered either at 08:00 and 20:00 or at 09:00 and 21:00, and prochlorperazine (5 mg) was also given at the same times for 5 days. Results: Of the 145 enrolled patients, 138 were suitable for analysis. The incidence of nausea was 18.1%, and that of vomiting was 5.8%. The incidence of nausea was higher, but not to a significant degree, in women than in men (P=0.07). Furthermore, the incidence of vomiting in women was equal to that in men (P=0.28), whereas the incidences of both nausea (P=0.99) and vomiting (P=0.89) in elderly patients were equal to those in younger patients. In addition, the incidence of nausea (P=0.52) and vomiting (P= 0.91) in patients with digestive system cancer was equal to that of patients with non-digestive system cancer. Conclusions: The incidence of nausea induced by oxycodone with prochlorperazine was 18.1% in opioid-naive Japanese inpatients. Female sex may be a risk factor for oxycodone-induced nausea. These results suggest that a clinical study would require 314 participants (157 in each group) to decrease the incidence from 18% to 8% (10% decrease) with a new preventive treatment (alpha error=0.05, beta error=0.2). (J Nippon Med Sch 2015; 82: 100―105)

A mobile ad hoc network (MANET) is a network that consists of mobile wireless terminals without the aid of the base station. It is expected that MANETs are utilized for various purpose such as traffic jam information announce for vehicles and safety confirmation system in the disaster. Each MANET uses a routing protocol adaptive for the purpose of use. Therefore, utilizing the common routing protocol for multiple MANETs is difficult, and each MANET uses a different routing protocol. In this paper, we propose an Autonomous Clustering based Inter-Domain Routing protocol to communicate between different MANETs. Because of the autonomous clustering, the proposed inter-domain routing scheme can adaptively change the network gateways between MANETs according to the network topology change.

Inhibitors of the mammalian target of rapamycin (mTOR) have been shown to protect against neuronal injury, but the mechanisms underlying this effect are not fully understood. The present study aimed to examine the effects of rapamycin, an inhibitor of the mTOR pathway, on inflammation and capillary degeneration in a rat model of N-methyl-D-aspartate (NMDA)-induced retinal neurotoxicity. Inflammation and capillary degeneration were evaluated by counting the numbers of CD45-positive leukocytes and Iba1-positive microglia, and by measuring the length of empty basement membrane sleeves, respectively. Marked increases in the numbers of leukocytes and microglia were observed 1 d after intravitreal injection of NMDA (200 nmol), and significant capillary degeneration was observed after 7 d. These NMDA-induced changes were significantly reduced by the simultaneous injection of rapamycin (20 nmol) with NMDA. These results suggest that rapamycin has preventive effects on inflammation and capillary degeneration during retinal injury.