CD271 mRNA/hnRNPA2B1 complex promotes proliferation and stemness in oral and head and neck squamous cell carcinoma.

RNAs, such as noncoding RNA, microRNA, and recently mRNA, have been recognized as signal transduction molecules. CD271, also known as nerve growth factor receptor, has a critical role in cancer, although the precise mechanism is still unclear. Here, we show that CD271 mRNA, but not CD271 protein, facilitates spheroid cell proliferation. We established CD271-/- cells lacking both mRNA and protein of CD271, as well as CD271 protein knockout cells lacking only CD271 protein, from hypopharyngeal and oral squamous cell carcinoma lines. Sphere formation was reduced in CD271-/- cells but not in CD271 protein knockout cells. Mutated CD271 mRNA, which is not translated to a protein, promoted sphere formation. CD271 mRNA bound to hnRNPA2B1 protein at the 3'-UTR region, and the inhibition of this interaction reduced sphere formation. In surgical specimens, the CD271 mRNA/protein expression ratio was higher in the cancerous area than in the noncancerous area. These data suggest CD271 mRNA has dual functions, encompassing protein-coding and noncoding roles, with its noncoding RNA function being predominant in oral and head and neck squamous cell carcinoma.

Simulation of Changes in Tensile Strain by Airbag Impact on Eyes After Trabeculectomy by Using Finite Element Analysis.

Purpose: We studied the kinetic phenomenon of an airbag impact on eyes after trabeculectomy using finite element analysis (FEA), a computerized method for predicting how an object reacts to real-world physical effects and showing whether an object will break, to sequentially determine the responses at various airbag deployment velocities. Methods: A human eye model was used in the simulations using the FEA program PAM-GENERISTM (Nihon ESI, Tokyo, Japan). A half-thickness incised scleral flap was created on the limbus and the strength of its adhesion to the outer sclera was set at 30%, 50%, and 100%. The airbag was set to hit the surface of the post-trabeculectomy eye at various velocities in two directions: perpendicular to the corneal center or perpendicular to the scleral flap (30° gaze-down position), at initial velocities of 20, 30, 40, 50, and 60 m/s. Results: When the airbag impacted at 20 m/s or 30 m/s, the strain on the cornea and sclera did not reach the mechanical threshold and globe rupture was not observed. Scleral flap lacerations were observed at 40 m/s or more in any eye position, and scleral rupture extending posteriorly from the scleral flap edge and rupture of the scleral flap resulting from extension of the corneal laceration through limbal damage were observed. Even in the case of 100% scleral flap adhesion strength, scleral flap rupture occurred at 50 m/s impact velocity in the 30° gaze-down position, whereas in eyes with 30% or 50% scleral flap adhesion strength, scleral rupture was observed at an impact velocity of 40 m/s or more in both eye positions. Conclusion: An airbag impact of ≥40 m/s might induce scleral flap rupture, indicating that current airbags may induce globe rupture in the eyes after trabeculectomy. The considerable damage caused by an airbag on the eyes of short-stature patients with glaucoma who have undergone trabeculectomy might indicate the necessity of ocular protection to avoid permanent eye damage.

FAXC interacts with ANXA2 and SRC in mitochondria and promotes tumorigenesis in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is one of the most difficult malignancies to treat as the therapeutic options are limited. Although several driver genes have been identified, most remain unknown. In this study, we identified a failed axon connection homolog (FAXC), whose function is unknown in mammals, by analyzing serially passaged CCA xenograft models. Knockdown of FAXC reduced subcutaneous tumorigenicity in mice. FAXC was bound to annexin A2 (ANXA2) and c-SRC, which are tumor-promoting genes. The FAXC/ANXA2/c-SRC complex forms in the mitochondria. FAXC enhances SRC-dependent ANXA2 phosphorylation at tyrosine-24, and the C-terminal amino acid residues (351-375) of FAXC are required for ANXA2 phosphorylation. Transcriptome data from a xenografted CCA cell line revealed that FAXC correlated with epithelial-mesenchymal transition, hypoxia, and KRAS signaling genes. Collectively, these findings advance our understanding of CCA tumorigenesis and provide candidate therapeutic targets.

Characteristics of tissue temperature during ablation with THERMOCOOL SMARTTOUCH SF versus TactiCath versus QDOT MICRO catheters (Qmode and Qmode+): An in vivo porcine study.

INTRODUCTION: High-power short-duration (HPSD) ablation at 50 W, guided by ablation index (AI) or lesion size index (LSI), and a 90 W/4 s very HSPD (vHPSD) setting are available for atrial fibrillation (AF) treatment. Yet, tissue temperatures during ablation with different catheters around venoatrial junction and collateral tissues remain unclear. METHODS: In this porcine study, we surgically implanted thermocouples on the epicardium near the superior vena cava (SVC), right pulmonary vein, and esophagus close to the inferior vena cava. We then compared tissue temperatures during 50W-HPSD guided by AI 400 or LSI 5.0, and 90 W/4 s-vHPSD ablation using THERMOCOOL SMARTTOUCH SF (STSF), TactiCath ablation catheter, sensor enabled (TacthCath), and QDOT MICRO (Qmode and Qmode+ settings) catheters. RESULTS: STSF produced the highest maximum tissue temperature (Tmax ), followed by TactiCath, and QDOT MICRO in Qmode and Qmode+ (62.7 ± 12.5°C, 58.0 ± 10.1°C, 50.0 ± 12.1°C, and 49.2 ± 8.4°C, respectively; p = .005), achieving effective transmural lesions. Time to lethal tissue temperature ≥50°C (t-T ≥ 50°C) was fastest in Qmode+, followed by TacthCath, STSF, and Qmode (4.3 ± 2.5, 6.4 ± 1.9, 7.1 ± 2.8, and 7.7 ± 3.1 s, respectively; p < .001). The catheter tip-to-thermocouple distance for lethal temperature (indicating lesion depth) from receiver operating characteristic curve analysis was deepest in STSF at 5.2 mm, followed by Qmode at 4.3 mm, Qmode+ at 3.1 mm, and TactiCath at 2.8 mm. Ablation at the SVC near the phrenic nerve led to sudden injury at t-T ≥ 50°C in all four settings. The esophageal adventitia injury was least deep with Qmode+ ablation (0.4 ± 0.1 vs. 0.8 ± 0.4 mm for Qmode, 0.9 ± 0.3 mm for TactiCath, and 1.1 ± 0.5 mm for STSF, respectively; p = .005), correlating with Tmax . CONCLUSION: This study revealed distinct tissue temperature patterns during HSPD and vHPSD ablations with the three catheters, affecting lesion effectiveness and collateral damage based on Tmax and/or t-T ≥ 50°C. These findings provide key insights into the safety and efficacy of AF ablation with these four settings.

CD271 promotes proliferation and migration in bladder cancer.

Bladder cancer is a urothelial cancer and effective therapeutic strategies for its advanced stages are limited. Here, we report that CD271, a neurotrophin receptor, promotes the proliferation and migration of bladder cancer cells. CD271 knockdown decreased proliferation in both adherent and spheroid cultures, and vice versa when CD271 was overexpressed in bladder cancer cell lines. CD271 depletion impaired tumorigenicity in vivo. Migration activity was reduced by CD271 knockdown and TAT-Pep5, a known CD271-Rho GDI-binding inhibitor. Apoptosis was induced by CD271 knockdown. Comprehensive gene expression analysis revealed alterations in E2F- and Myc-related pathways upon CD271 expression. In clinical cases, patients with high CD271 expression showed significantly shortened overall survival. In surgically resected specimens, pERK, a known player in proliferation signaling, colocalizes with CD271. These data indicate that CD271 is involved in bladder cancer malignancy by promoting cell proliferation and migration, resulting in poor prognosis.

BEX2 is poor prognostic factor and required for cancer stemness in gastric cancer.

Gastric cancer is the fifth most common malignancy worldwide. However, targeted therapy for advanced gastric cancer is still limited. Here, we report BEX2 (Brain expressed X-linked 2) as a poor prognostic factor in two gastric cancer cohorts. BEX2 expression was increased in spheroid cells, and its knockdown decreased aldefluor activity and cisplatin resistance. BEX2 was found to upregulate CHRNB2 (Cholinergic Receptor Nicotinic Beta 2 Subunit) expression, a cancer stemness-related gene, in a transcriptional manner, and the knockdown of which also decreases aldefluor activity. Collectively, these data are suggestive of the role of BEX2 in the malignant process of gastric cancer, and as a promising therapeutic target.

In vivo tissue temperatures during 90 W/4 sec-very high power-short-duration (vHPSD) ablation versus ablation index-guided 50 W-HPSD ablation: A porcine study.

INTRODUCTION: Neither the actual in vivo tissue temperatures reached with 90 W/4 s-very high-power short-duration (vHPSD) ablation for atrial fibrillation nor the safety and efficacy profile have been fully elucidated. METHODS: We conducted a porcine study (n = 15) in which, after right thoracotomy, we implanted 6-8 thermocouples epicardially in the superior vena cava, right pulmonary vein, and esophagus close to the inferior vena cava. We compared tissue temperatures close to a QDOT MICRO catheter, between during 90 W/4 s-vHPSD ablation during ablation index (AI: target 400)-guided 50 W-HPSD ablation, both targeting a contact force of 8-15 g. RESULTS: Maximum tissue temperature reached during 90 W/4 s-vHPSD ablation did not differ significantly from that during 50 W-HPSD ablation (49.2 ± 8.4°C vs. 50.0 ± 12.1°C; p = .69) and correlated inversely with distance between the catheter tip and the thermocouple, regardless of the power settings (r = -0.52 and r = -0.37). Lethal temperature (≥50°C) was best predicted at a catheter tip-to-thermocouple distance cut-point of 3.13 and 4.27 mm, respectively. All lesions produced by 90 W/4 s-vHPSD or 50 W-HPSD ablation were transmural. Although there was no difference in the esophageal injury rate (50% vs. 66%, p = .80), the thermal lesion was significantly shallower with 90 W/4 s-vHPSD ablation than with 50W-HPSD ablation (381.3 ± 127.3 vs. 820.0 ± 426.1 µm from the esophageal adventitia; p = .039). CONCLUSION: Actual tissue temperatures reached with 90 W/4 s-vHPSD ablation appear similar to those with AI-guided 50 W-HPSD ablation, with the distance between the catheter tip and target tissue being shorter for the former. Although both ablation settings may create transmural lesions in thin atrial tissues, any resulting esophageal thermal lesions appear shallower with 90 W/4 s-vHPSD ablation.

In vivo tissue temperature during lesion size index-guided 50W ablation versus 30W ablation: A porcine study.

BACKGROUND: Neither the actual in vivo tissue temperatures reached with lesion size index (LSI)-guided high-power short-duration (HPSD) ablation for atrial fibrillation nor the safety profile has been elucidated. METHODS: We conducted a porcine study (n = 7) in which, after right thoracotomy, we implanted 6-8 thermocouples epicardially in the superior vena cava, right pulmonary vein, and esophagus close to the inferior vena cava. We compared tissue temperatures reached during 50 W-HPSD ablation with those reached during standard (30 W) ablation, both targeting an LSI of 5.0 (5-15 g contact force). RESULTS: Tmax  (maximum tissue temperature when the thermocouple was located ≤5 mm from the catheter tip) reached during HPSD ablation was modestly higher than that reached during standard ablation (58.0 ± 10.1°C vs. 53.6 ± 9.2°C; p = .14) and peak tissue temperature correlated inversely with the distance between the catheter tip and the thermocouple, regardless of the power settings (HPSD: r = -0.63; standard: r = -0.66). Lethal temperature (≥50°C) reached 6.3 ± 1.8 s and 16.9 ± 16.1 s after the start of HPSD and standard ablation, respectively (p = .002), and it was best predicted at a catheter tip-to-thermocouple distance cut point of 2.8 and 5.3 mm, respectively. All lesions produced by HPSD ablation and by standard ablation were transmural. There was no difference between HPSD ablation and standard ablation in the esophageal injury rate (70% vs. 75%, p = .81), but the maximum distance from the esophageal adventitia to the injury site tended to be shorter (0.94 ± 0.29 mm vs. 1.40 ± 0.57 mm, respectively; p = .09). CONCLUSIONS: Actual tissue temperatures reached with LSI-guided HPSD ablation appear to be modestly higher, with a shorter distance between the catheter tip and thermocouple achieving lethal temperature, than those reached with standard ablation. HPSD ablation lasting <6 s may help minimize lethal thermal injury to the esophagus lying at a close distance.

RELA is required for CD271 expression and stem-like characteristics in hypopharyngeal cancer.

CD271 (also referred to as nerve growth factor receptor or p75NTR) is expressed on cancer stem cells in hypopharyngeal cancer (HPC) and regulates cell proliferation. Because elevated expression of CD271 increases cancer malignancy and correlates with poor prognosis, CD271 could be a promising therapeutic target; however, little is known about the induction of CD271 expression and especially its promoter activity. In this study, we screened transcription factors and found that RELA (p65), a subunit of nuclear factor kappaB (NF-κB), is critical for CD271 transcription in cancer cells. Specifically, we found that RELA promoted CD271 transcription in squamous cell carcinoma cell lines but not in normal epithelium and neuroblastoma cell lines. Within the CD271 promoter sequence, region + 957 to + 1138 was important for RELA binding, and cells harboring deletions in proximity to the + 1045 region decreased CD271 expression and sphere-formation activity. Additionally, we found that clinical tissue samples showing elevated CD271 expression were enriched in RELA-binding sites and that HPC tissues showed elevated levels of both CD271 and phosphorylated RELA. These data suggested that RELA increases CD271 expression and that inhibition of RELA binding to the CD271 promoter could be an effective therapeutic target.

Establishment of a monoclonal antibody against glycosylated CD271 specific for cancer cells in immunohistochemistry.

Various proteins are highly expressed in cancer (e.g., epidermal growth factor receptor); however, the majority are also expressed in normal cells, although they may differ in expression intensity. Recently, we reported that CD271 (nerve growth factor receptor), a glycosylated protein, increases malignant behavior of cancer, particularly stemlike phenotypes in squamous cell carcinoma (SCC). CD271 is expressed in SCC and in normal epithelial basal cells. Glycosylation alterations generally occur in cancer cells; therefore, we attempted to establish a cancer-specific anti-glycosylated CD271 antibody. We purified recombinant glycosylated CD271 protein, immunized mice with the protein, and screened hybridomas using an ELISA assay with cancer cell lines. We established a clone G4B1 against CD271 which is glycosylated with O-glycan and sialic acid. The G4B1 antibody reacted with the CD271 protein expressed in esophageal cancer, but not in normal esophageal basal cells. This specificity was confirmed in hypopharyngeal and cervical cancers. G4B1 antibody recognized the fetal esophageal epithelium and Barrett's esophagus, which possess stem cell-like characteristics. In conclusion, G4B1 antibody could be useful for precise identification of dysplasia and cancer cells in SCC.

Transplantation of Mature Adipocyte-Derived Dedifferentiated Fat Cells Facilitates Periodontal Tissue Regeneration of Class II Furcation Defects in Miniature Pigs.

Adipose tissue is composed mostly of adipocytes that are in contact with capillaries. By using a ceiling culture method based on buoyancy, lipid-free fibroblast-like cells, also known as dedifferentiated fat (DFAT) cells, can be separated from mature adipocytes with a large single lipid droplet. DFAT cells can re-establish their active proliferation ability and transdifferentiate into various cell types under appropriate culture conditions. Herein, we sought to compare the regenerative potential of collagen matrix alone (control) with autologous DFAT cell-loaded collagen matrix transplantation in adult miniature pigs (microminipigs; MMPs). We established and transplanted DFAT cells into inflammation-inducing periodontal class II furcation defects. At 12 weeks after cell transplantation, a marked attachment gain was observed based on the clinical parameters of probing depth (PD) and clinical attachment level (CAL). Additionally, micro computed tomography (CT) revealed hard tissue formation in furcation defects of the second premolar. The cemento-enamel junction and alveolar bone crest distance was significantly shorter following transplantation. Moreover, newly formed cellular cementum, well-oriented periodontal ligament-like fibers, and alveolar bone formation were observed via histological analysis. No teratomas were found in the internal organs of recipient MMPs. Taken together, these findings suggest that DFAT cells can safely enhance periodontal tissue regeneration.

Effect of Rivaroxaban and Clopidogrel Combination Therapy on In-Stent Responses After Everolimus-Eluting Stent Implantation in a Porcine Coronary Model.

AIM: According to recent clinical trials, a combination of direct oral anticoagulants with antiplatelet drugs is often recommended for atrial fibrillation patients who receive drug-eluting stents (DESs). Although the optimal combination comprises direct factor Xa inhibitors and a P2Y12 receptor antagonist (or aspirin), their influence on vascular responses to DESs remains unclear. METHODS: Pigs were given either aspirin and clopidogrel (dual antiplatelet therapy [DAPT] group), aspirin and rivaroxaban (AR group), or clopidogrel and rivaroxaban (CR group), followed by everolimus-eluting stent (Promus Element) implantation into the coronary artery. Stented coronary arteries were evaluated via intravascular optical coherence tomography (OCT) and histological analysis at 1 and 3 months. RESULTS: OCT revealed lower neointimal thickness in the DAPT group and comparable thickness among all groups at 1 and 3 months, respectively. Histological analyses revealed comparable neointimal area among all groups and the smallest neointimal area in the CR group at 1 and 3 months, respectively. In the DAPT and AR groups, the neointima continued to grow from 1 to 3 months. A shortened time course for neointima growth was observed in the CR group, with rapid growth within a month (maintained for 3 months). A higher incidence of in-stent thrombi was observed in the AR group at 1 month; no thrombi were found in either group at 3 months. More smooth muscle cells with contractile features were found in the CR group at both 1 and 3 months. CONCLUSIONS: Our results proved the noninferiority of the combination of rivaroxaban with an antiplatelet drug, particularly the dual therapy using rivaroxaban and clopidogrel, compared to DAPT after DES implantation.

Actual tissue temperature during ablation index-guided high-power short-duration ablation versus standard ablation: Implications in terms of the efficacy and safety of atrial fibrillation ablation.

BACKGROUND: Actual in vivo tissue temperatures and the safety profile during high-power short-duration (HPSD) ablation of atrial fibrillation have not been clarified. METHODS: We conducted an animal study in which, after a right thoracotomy, we implanted 6-8 thermocouples epicardially in the superior vena cava, right pulmonary vein, and esophagus close to the inferior vena cava. We recorded tissue temperatures during a 50 W-HPSD ablation and 30 W-standard ablation targeting an ablation index (AI) of 400 (5-15 g contact force). RESULTS: Maximum tissue temperatures reached with HSPD ablation were significantly higher than that reached with standard ablation (62.7 ± 12.5 vs. 52.7 ± 11.4°C, p = 0.033) and correlated inversely with the distance between the catheter tip and thermocouple, regardless of the power settings (HPSD: r = -0.71; standard: r = -0.64). Achievement of lethal temperatures (≥50°C) was within 7.6 ± 3.6 and 12.1 ± 4.1 s after HPSD and standard ablation, respectively (p = 0.003), and was best predicted at cutoff points of 5.2 and 4.4 mm, respectively. All HPSD ablation lesions were transmural, but 19.2% of the standard ablation lesions were not (p = 0.011). There was no difference between HPSD and standard ablation regarding the esophageal injury rate (30% vs. 33.3%, p > 0.99), with the injury appearing to be related to the short distance from the catheter tip. CONCLUSIONS: Actual tissue temperatures reached with AI-guided HPSD ablation appeared to be higher with a greater distance between the catheter tip and target tissue than those with standard ablation. HPSD ablation for <7 s may help prevent collateral tissue injury when ablating within a close distance.

BEX2 is required for maintaining dormant cancer stem cell in hepatocellular carcinoma.

Cancer stem cells (CSCs) are responsible for therapy resistance and share several properties with normal stem cells. Here, we show that brain-expressed X-linked gene 2 (BEX2), which is essential for dormant CSCs in cholangiocarcinoma, is highly expressed in human hepatocellular carcinoma (HCC) lesions compared with the adjacent normal lesions and that in 41 HCC cases the BEX2high expression group is correlated with a poor prognosis. BEX2 localizes to Ki67-negative (nonproliferative) cancer cells in HCC tissues and is highly expressed in the dormant fraction of HCC cell lines. Knockdown of BEX2 attenuates CSC phenotypes, including sphere formation ability and aldefluor activity, and BEX2 overexpression enhances these phenotypes. Moreover, BEX2 knockdown increases cisplatin sensitivity, and BEX2 expression is induced by cisplatin treatment. Taken together, these data suggest that BEX2 induces dormant CSC properties and affects the prognosis of patients with HCC.

Effect of obesity and epicardial fat/fatty infiltration on electrical and structural remodeling associated with atrial fibrillation in a novel canine model of obesity and atrial fibrillation: A comparative study.

BACKGROUND: How obesity and epicardial fat influence atrial fibrillation (AF) is unknown. METHODS: To investigate the effect of obesity/epicardial fat on the AF substrate, we divided 20 beagle dogs of normal weight into four groups (n = 5 each): one of the four groups (Obese-rapid atrial pacing [RAP] group) served as a novel canine model of obesity and AF. The other three groups comprised dogs fed a standard diet without RAP (Control group), dogs fed a high-fat diet without RAP (Obese group), or dogs fed a standard diet with RAP (RAP group). All underwent electrophysiology study, and hearts were excised for histopathologic and fibrosis-related gene expression analyses. RESULTS: Left atrial (LA) pressure was significantly higher in the Obese group than in the Control, RAP, and Obese-RAP groups (23.4 ± 6.9 vs. 11.4 ± 2.1, 11.9 ± 6.4, and 13.5 ± 2.9 mmHg; p = .005). The effective refractory period of the inferior PV was significantly shorter in the RAP and Obese-RAP groups than in the Control group (p = .043). Short-duration AF was induced at greatest frequency in the Obese-RAP and Obese groups (p < .05). Epicardial fat/Fatty infiltration was greatest in the Obese-RAP group, and greater in the Obese and RAP groups than in the Control group. %interstitial fibrosis/fibrosis-related gene expression was significantly greater in the Obese-RAP and RAP groups (p < .05). CONCLUSIONS: Vulnerability to AF was associated with increased LA pressure and increased epicardial fat/fatty infiltration in our Obese group, and with increased epicardial fat/fibrofatty infiltration in the RAP and Obese-RAP groups. These may explain the role of obesity/epicardial fat in the pathogenesis of AF.

Discovery of a chemical compound that suppresses expression of BEX2, a dormant cancer stem cell-related protein.

Cancer stem cells (CSCs) are believed to cause cancer metastasis and recurrence. BEX2 (brain expressed X-linked gene 2) is a CSC-related gene that is expressed in dormant CSCs in cholangiocarcinoma and induces resistance against chemotherapy. The aim of the present study was to identify small compounds that have activity to inhibit BEX2 expression and result in the attenuation of CSC-related phenotypes. We screened 9600 small chemical compounds in high-throughput screening using cholangiocarcinoma cell line HuCCT1 expressing BEX2 protein fused with NanoLuc, and identified a compound, BMPP (1, 3-Benzenediol, [4-(4-methoxyphenyl)-1H-pyrazol-3-yl]). BMPP was found to exert decreasing effects on BEX2 protein expression and G0 phase population of the tumor cells, and increasing effects on ATP levels and chemotherapeutic sensitivity of the cells. These findings indicate that BMPP is a valuable chemical compound for reducing dormant CSC-related phenotypes. Thus, the identification of BMPP as a potential CSC suppressor provides scope for the development of novel therapeutic modalities for the treatment of cancers with BEX2 overexpressing CSCs.

BEX2 suppresses mitochondrial activity and is required for dormant cancer stem cell maintenance in intrahepatic cholangiocarcinoma.

Cancer stem cells (CSCs) define a subpopulation of cancer cells that are resistant to therapy. However, little is known of how CSC characteristics are regulated. We previously showed that dormant cancer stem cells are enriched with a CD274low fraction of cholangiocarcinoma cells. Here we found that BEX2 was highly expressed in CD274low cells, and that BEX2 knockdown decreased the tumorigenicity and G0 phase of cholangiocarcinoma cells. BEX2 was found to be expressed predominantly in G0 phase and starvation induced the USF2 transcriptional factor, which induced BEX2 transcription. Comprehensive screening of BEX2 binding proteins identified E3 ubiquitin ligase complex proteins, FEM1B and CUL2, and a mitochondrial protein TUFM, and further demonstrated that knockdown of BEX2 or TUFM increased mitochondria-related oxygen consumption and decreased tumorigenicity in cholangiocarcinoma cells. These results suggest that BEX2 is essential for maintaining dormant cancer stem cells through the suppression of mitochondrial activity in cholangiocarcinoma.

Finite Element Analysis of Changes in Tensile Strain by Airsoft Gun Impact on Eye and Deformation Rate in Eyes of Various Axial Lengths.

PURPOSE: We have carried out three-dimensional finite element analysis (FEA) to determine the physical and mechanical response in several ocular injuries. We applied this FEA model to evaluate an airsoft gun impact on an eye and the deformation rate of eyes of various axial lengths at various velocities. METHODS: This study was carried out on a human eye model using an FEA program created by Nihon, ESI Group. The airsoft gun pellet was set to impact the eye at initial velocities of 45, 60 and 75 m/s with the addition of variation in axial length of 20 mm (hyperopia), 22 mm (emmetropia), 24 mm (myopia) and 26 mm (high myopia). Deformation of the eye was calculated as the decrease rate of the volume of the eyeball and the decrease rate of the axial length. RESULTS: In all emmetropic cases, the cornea reached its strain threshold during the impact, and scleral strain showed a patchy strength distribution in the simulation. The deformation was most evident in the anterior segment, while deformation of the posterior segment was less. The decrease rate of the volume of the eyeball and decrease rate of the axial length were highest in the hyperopic eye, followed by the emmetropic eye and myopic eye, and the high myopic eye showed the lowest decrease rates among the four axial lengths in all impact velocity simulations. CONCLUSION: These results suggest that hyperopic eyes are most susceptible to deformation by an airsoft gun impact compared with other axial length eye models in this simulation. The considerable deformation by an airsoft gun impact shown in this study might indicate the necessity of ocular protection to avoid permanent eye injury. FEA using a human eyeball model might be a useful method to analyze and predict the mechanical features of ocular injury by an airsoft gun.

Finite Element Analysis of Air Gun Impact on Post-Keratoplasty Eye.

PURPOSE: Due to the mechanical vulnerability of eyes that have undergone penetrating keratoplasty (PKP), it is clinically important to evaluate the possibility of corneal wound dehiscence by blunt impact. We have previously developed a simulation model resembling a human eye based on information obtained from cadaver eyes and applied three-dimensional finite element analysis (FEA) to determine the physical and mechanical response to an air gun impact at various velocities on the post-PKP eye. METHODS: Simulations in a human eye model were performed with a computer using a FEA program created by Nihon, ESI Group. The air gun pellet was set to impact the eye at three-different velocities in straight or 12° up-gaze positions with the addition of variation in keratoplasty suture strength of 30%, 50% and 100% of normal corneal strength. RESULTS: Furthermore to little damage in the case of 100% strength, in cases of lower strength in a straight-gaze position, wound rupture seemed to occur in the early phase (0.04-0.06 ms) of impact at low velocities, while regional break was observed at 0.14 ms after an impact at high velocity (75 m/s). In contrast, wound damage was observed in the lower quadrant of the suture zone and sclera in 12° up-gaze cases. Wound damage was observed 0.08 ms after an impact threatening corneoscleral laceration, and the involved area being larger in middle impact velocity (60 m/s) simulations than in lower impact velocity simulations, and larger damaged area was observed in high impact velocity cases and leading to corneoscleral laceration. CONCLUSION: These results suggest that the eye is most susceptible to corneal damage around the suture area especially with a straight-gaze impact by an air gun, and that special precautionary measures should be considered in patients who undergo PKP. FEA using a human eyeball model might be a useful method to analyze and predict the mechanical features of eyes that undergo keratoplasty.