Overstretching alveolar epithelial type II cells decreases surfactant secretion via actin polymerization and intracellular trafficking alteration.

Pulmonary surfactant is essential for maintaining proper lung function. Alveolar epithelial type II (AE2) cells secrete surfactants via lamellar bodies (LBs). In tidal loading during each breath, the physiological cyclic stretching of AE2 cells promotes surfactant secretion. Excessive stretching inhibits surfactant secretion, which is considered to contribute to the development of lung damage. However, its precise mechanism remains unknown. This study tested whether actin polymerization and intracellular transport are required for pulmonary surfactant secretion and the association of actin polymerization and transport in identical human AE2-derived A549 cells using live-cell imaging, not in the bulk cells population. We found that overstretching approximately doubled actin polymerization into filaments (F-actin) and suppressed LB secretion by half in the fluorescent area ratio, compared with physiological stretching (F-actin: 1.495 vs 0.643 (P < 0.01); LB: 0.739 vs 0.332 (P < 0.01)). An inhibitor of actin polymerization increased LB secretion. Intracellular tracking using fluorescent particles revealed that cyclic stretching shifted the particle motion perpendicularly to the direction of stretching according to the orientation of the F-actin (proportion of perpendicular axis motion prior particle: 0h 40.12 % vs 2h 63.13 % (P < 0.01)), and particle motion was restricted over time in the cells subjected to overstretching, indicating that overstretching regulates intracellular transport dynamics (proportion of stop motion particle: 0h 1.01 % vs 2h 11.04 % (P < 0.01)). These findings suggest that overstretching changes secretion through the cytoskeleton: overstretching AE2 cells inhibits pulmonary surfactant secretion, at least through accelerating actin polymerization and decreasing intracellular trafficking, and the change in actin orientation would modulate intracellular trafficking.

Spatiotemporal distribution of PTEN before directed cell migration in monolayers.

The intracellular distribution of phosphatase and tensin homolog (PTEN) is closely related to directed cell migration. In single cells, PTEN accumulates at the rear of the cell before and during directed migration; however, the spatiotemporal distribution of PTEN in confluent cell monolayers, particularly before directed migration, remains unclear. In this study, we wounded a cell in confluent fetal rat skin keratinocytes (FRSKs) and examined the dynamics of PTEN in the cells adjacent to the wounded cell. In contrast to single-cell migration, we found that PTEN translocated to the nucleus before the beginning of directed migration. This nuclear translocation of PTEN did not occur in disconnected cells, and it was also suppressed by importin-ß inhibitor and actin inhibitor. When the nuclear localization of PTEN was inhibited by an importin-ß inhibitor, cell elongation in the direction of migration was also significantly inhibited. Our results indicate that PTEN translocation is induced by the disruption of cell-cell adhesion and requires the involvement of importin-ß and actin cytoskeleton signaling. In addition, phosphatidylinositol 3,4,5-triphosphate (PIP3) may regulate PTEN distribution through its localized accumulation at the cell edge. Our findings suggest that the translocation of PTEN is crucial for directed cell migration and for responding to mechanical environmental changes in confluent cell monolayers.

Cold-induced vasodilation response in a Japanese cohort: insights from cold-water immersion and genome-wide association studies.

BACKGROUND: Cold-induced vasodilation (CIVD) occurs after blood vessels in the skin are constricted due to local cold exposure. Although many CIVD studies have been conducted, the underlying molecular mechanisms are yet to be clarified. Therefore, we explored genetic variants associated with CIVD response using the largest-scale dataset reported to date in a CIVD study involving wavelet analysis; thus, the findings improve our understanding of the molecular mechanisms that regulate the CIVD response. METHODS: We performed wavelet analysis of three skin blood flow signals [endothelial nitric oxide (eNO)-independent, eNO-dependent, and neurogenic activities] during finger cold-water immersion at 5 °C in 94 Japanese young adults. Additionally, we conducted genome-wide association studies of CIVD using saliva samples collected from the participants. RESULTS: We found that the mean wavelet amplitudes of eNO-independent and neurogenic activities significantly increased and decreased prior to CIVD, respectively. Our results also implied that as many as ~ 10% of the Japanese subjects did not show an apparent CIVD response. Our genome-wide association studies of CIVD using ~ 4,040,000 imputed data found no apparent CIVD-related genetic variants; however, we identified 10 genetic variants, including 2 functional genes (COL4A2 and PRLR) that are associated with notable blunted eNO-independent and neurogenic activity responses in individuals without CIVD response during local cold exposure. CONCLUSIONS: Our findings indicate that individuals without CIVD response differentiated by genotypes with COL4A2 and PRLR genetic variants exhibited notable blunted eNO-independent and neurogenic activity responses during local cold exposure.

A maternal high-fat diet induces fetal origins of NASH-HCC in mice.

Maternal overnutrition affects offspring susceptibility to nonalcoholic steatohepatitis (NASH). Male offspring from high-fat diet (HFD)-fed dams developed a severe form of NASH, leading to highly vascular tumor formation. The cancer/testis antigen HORMA domain containing protein 1 (HORMAD1), one of 146 upregulated differentially expressed genes in fetal livers from HFD-fed dams, was overexpressed with hypoxia-inducible factor 1 alpha (HIF-1alpha) in hepatoblasts and in NASH-based hepatocellular carcinoma (HCC) in offspring from HFD-fed dams at 15 weeks old. Hypoxia substantially increased Hormad1 expression in primary mouse hepatocytes. Despite the presence of three putative hypoxia response elements within the mouse Hormad1 gene, the Hif-1alpha siRNA only slightly decreased hypoxia-induced Hormad1 mRNA expression. In contrast, N-acetylcysteine, but not rotenone, inhibited hypoxia-induced Hormad1 expression, indicating its dependency on nonmitochondrial reactive oxygen species production. Synchrotron-based phase-contrast micro-CT of the fetuses from HFD-fed dams showed significant enlargement of the liver accompanied by a consistent size of the umbilical vein, which may cause hypoxia in the fetal liver. Based on these findings, a maternal HFD induces fetal origins of NASH/HCC via hypoxia, and HORMAD1 is a potential therapeutic target for NASH/HCC.

Influence of the difference in refractive index on the interface of an object and the surroundings in near-infrared fluorescence tomography.

The refraction of fluorescence from the inside of a sample at the surface results in fluctuations in fluorescence computed tomography (CT). We evaluated the influence of the difference in refractive index (RI) between the sample body and the surroundings on fluorescence CT results. The brightest fluorescent point is away from the correct point on the tomograms owing to the refraction. The speculated position is determined as the exact point if the RI ratio ranges between 0.97 and 1.03 by immersing the body in an RI matching liquid. The results can help in experimental settings of fluorescence CT for acquiring three-dimensional positional information.

Spatiotemporal distribution of PKCα, Cdc42, and Rac1 before directed cell migration.

Cdc42 is a key factor in directed cell migration and accumulates at the leading edge of migrating cells. However, what kind of proteins control Cdc42 and when is unclear. After mechanical wounding, protein kinase C α (PKCα), a conventional PKC isozyme, begins to accumulate at the edges of cells adjacent to the wounded cells (WCs). In this study, we hypothesized that PKCα may be implicated in directed cell migration at an early stage before Cdc42 controls the migration. We focused on the spatiotemporal distribution of PKCα, Cdc42, and Rac1 before cell migration. After wounding, at the edges of cells adjacent to the WCs, PKCα accumulation, Cdc42 accumulation, Rac1 accumulation, and filopodia formation occurred in that order. The PKCα inhibitor suppressed Cdc42 accumulation at the cell edges. These results suggest that inhibition of PKCα activity inhibits cell migration. In addition, it is not Cdc42 but PKCα that may decide the direction of cell migration.

Visualizing the Flow Patterns in an Expanding and Contracting Pulmonary Alveolated Duct Based on Microcomputed Tomography Images.

We visualized the flow patterns in an alveolated duct model with breathing-like expanding and contracting wall motions using particle image velocimetry, and then, we investigated the effect of acinar deformation on the flow patterns. We reconstructed a compliant, scaled-up model of an alveolated duct from synchrotron microcomputed tomography images of a mammalian lung. The alveolated duct did not include any bifurcation, and its entire surface was covered with alveoli. We embedded the alveolated duct in a sealed container that was filled with fluid. We oscillated the fluid in the duct and container simultaneously and independently to control the flow and duct volume. We examined the flow patterns in alveoli, with the Reynolds number (Re) at 0.03 or 0.22 and the acinar volume change at 0%, 20%, or 80%. At the same Re, the heterogeneous deformation induced different inspiration and expiration flow patterns, and the recirculating regions in alveoli changed during respiratory cycle. During a larger acinar deformation at Re = 0.03, the flow patterns tended to change from recirculating flow to radial flow during inspiration and vice versa during expiration. Additionally, the alveolar geometric characteristics, particularly the angle between the alveolar duct and mouth, affected these differences in flow patterns. At Re = 0.22, recirculating flow patterns tended to form during inspiration and expiration, regardless of the magnitude of the acinar deformation. Our in vitro experiments suggest that the alveolated flows with nonself-similar and heterogeneous wall motions may promote particle mixing and deposition.

Voxel-based simulation of flow and temperature in the human nasal cavity.

The nasal airway is an extremely complex structure, therefore grid generation for numerical prediction of airflow in the nasal cavity is time-consuming. This paper describes the development of a voxel-based model with a Cartesian structured grid, which is characterized by robust and automatic grid generation, and the simulation of the airflow and air-conditioning in an individual human nasal airway. Computed tomography images of a healthy adult nose were used to reconstruct a virtual three-dimensional model of the nasal airway. Simulations of quiet restful inspiratory flow were then performed using a Neumann boundary condition for the energy equation to adequately resolve the flow and heat transfer. General agreements of airflow patterns, which were a high-speed jet posterior to the nasal valve and recirculating flow that occupied the anterior part of the upper cavity, and temperature distributions of the airflow and septum wall were confirmed by comparing in-vivo measurements with numerical simulation results.

Low-frequency oscillations of finger skin blood flow during the initial stage of cold-induced vasodilation at different air temperatures.

BACKGROUND: Cold-induced vasodilation (CIVD) is known to be influenced by the ambient temperature. Frequency analysis of blood flow provides information on physiological regulation of the cardiovascular system, such as myogenic, neurogenic, endothelial nitric oxide (NO) dependent, and NO-independent activities. In this study, we hypothesized that the major origin of CIVD occurs prior to the CIVD event and investigated finger skin blood flow during the initial stage of CIVD at different ambient temperatures using frequency analysis. METHODS: Eighteen healthy volunteers immersed their fingers in 5 °C water at air temperatures of 20 °C and 25 °C. Finger skin blood flow was measured using laser Doppler flowmetry and analyzed using Morlet mother wavelet. We defined the time when the rate of blood flow increased dramatically as the onset of CIVD, and defined three phases as the periods from the onset of cooling to minimum blood flow (vasoconstriction), from minimum blood flow to the onset of CIVD (prior to CIVD), and from the onset of CIVD to maximum blood flow (CIVD). RESULTS: The increment ratio of blood flow at CIVD was significantly higher at 20 °C air temperature. In particular, at 20 °C air temperature, arteriovenous anastomoses (AVAs) might be closed at baseline, as finger skin temperature was much lower than at 25 °C air temperature, and endothelial NO-independent activity was significantly higher and neurogenic activity significantly lower during vasoconstriction than at baseline. Additionally, the differences in both activities between vasoconstriction and prior to CIVD were significant. On the other hand, there were no significant differences in endothelial NO-dependent activity between baseline and all phases at both air temperatures. CONCLUSIONS: Our results indicated that the increase of endothelial NO-independent activity and the decrease of neurogenic activity may contribute to the high increment ratio of blood flow at CIVD at 20 °C air temperature.

A metabolic reaction-diffusion model for PKCα translocation via PIP2 hydrolysis in an endothelial cell.

Hydrolysis of the phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) at the cell membrane induces the release of inositol 1,4,5-trisphosphate (IP3) into the cytoplasm and diffusion of diacylglycerol (DAG) through the membrane, respectively. Release of IP3 subsequently increases Ca2+ levels in the cytoplasm, which results in activation of protein kinase C α (PKCα) by Ca2+ and DAG, and finally the translocation of PKCα from the cytoplasm to the membrane. In this study, we developed a metabolic reaction-diffusion framework to simulate PKCα translocation via PIP2 hydrolysis in an endothelial cell. A three-dimensional cell model, divided into membrane and cytoplasm domains, was reconstructed from confocal microscopy images. The associated metabolic reactions were divided into their corresponding domain; PIP2 hydrolysis at the membrane domain resulted in DAG diffusion at the membrane domain and IP3 release into the cytoplasm domain. In the cytoplasm domain, Ca2+ was released from the endoplasmic reticulum, and IP3, Ca2+, and PKCα diffused through the cytoplasm. PKCα bound Ca2+ at, and diffused through, the cytoplasm, and was finally activated by binding with DAG at the membrane. Using our model, we analyzed IP3 and DAG dynamics, Ca2+ waves, and PKCα translocation in response to a microscopic stimulus. We found a qualitative agreement between our simulation results and our experimental results obtained by live-cell imaging. Interestingly, our results suggest that PKCα translocation is dominated by DAG dynamics. This three-dimensional reaction-diffusion mathematical framework could be used to investigate the link between PKCα activation in a cell and cell function.

Computed tomography for in vivo deep over-1000 nm near-infrared fluorescence imaging.

This study aims to develop a novel cross-sectional imaging of fluorescence in over-1000 nm near-infrared (OTN-NIR), which allows in vivo deep imaging, using computed tomography (CT) system. Cylindrical specimens of composite of OTN-NIR fluorophore, NaGdF4 co-doped with Yb3+ and Ho3+ (ex: 980 nm, em: 1150 nm), were embedded in cubic agar (10.5-12 mm) or in the peritoneal cavity of mice and placed on a rotatable stage. When the fluorescence from inside of the samples was serially captured from multiple angles, the images were disrupted by the reflection and refraction of emitted light on the sample-air interface. Immersing the sample into water filled in a rectangular bath suppressed the disruption at the interface and successfully reconstructed the position and concentration of OTN-NIR fluorophores on the cross-sectional images using a CT technique. This is promising as a novel three-dimensional imaging technique for OTN-NIR fluorescent image projections of small animals captured from multiple angles.

Voxel-based modeling of airflow in the human nasal cavity.

This paper describes the simulation of airflow in human nasal airways using voxel-based modeling characterized by robust, automatic, and objective grid generation. Computed tomography scans of a healthy adult nose are used to reconstruct 3D virtual models of the nasal airways. Voxel-based simulations of restful inspiratory flow are then performed using various mesh sizes to determine the level of granularity required to adequately resolve the airflow. For meshes with close voxel spacings, the model successfully reconstructs the nasal structure and predicts the overall pressure drop through the nasal cavity.

The Effectiveness of An Averaged Airway Model in Predicting the Airflow and Particle Transport Through the Airway.

Background: In this study, we proposed an averaged airway model design based on four healthy subjects and numerically evaluated its effectiveness for predicting the airflow and particle transport through an airway. Methods: Direct-averaged models of the conducting airways of four subjects were restored by averaging the three-dimensional (3D) skeletons of four healthy airways, which were calculated using an inverse 3D thinning algorithm. We simulated the airflow and particle transport in the individual and the averaged airway models using computational fluid dynamics. Results: The bifurcation geometry differs even among healthy subjects, but the averaged model retains the typical geometrical characteristics of the airways. The Reynolds number of the averaged model varied within the range found in the individual subject models, and the averaged model had similar inspiratory flow characteristics as the individual subject models. The deposition fractions at almost all individual lobes ranged within the variation observed in the subjects, however, the deposition fraction was higher in only one lobe. The deposition distribution at the main bifurcation point differed among the healthy subjects, but the characteristics of the averaged model fell within the variation observed in the individual subject models. On the contrary, the deposition fraction of the averaged model was higher than that of the average of the individual subject models and deviated from the range observed in the subject models. Conclusion: These results indicate that the direct-averaged model may be useful for predicting the individual airflow and particle transport on a macroscopic scale.

Heterogeneous structure and surface tension effects on mechanical response in pulmonary acinus: A finite element analysis.

BACKGROUND: The pulmonary acinus is a dead-end microstructure that consists of ducts and alveoli. High-resolution micro-CT imaging has recently provided detailed anatomical information of a complete in vivo acinus, but relating its mechanical response with its detailed acinar structure remains challenging. This study aimed to investigate the mechanical response of acinar tissue in a whole acinus for static inflation using computational approaches. METHODS: We performed finite element analysis of a whole acinus for static inflation. The acinar structure model was generated based on micro-CT images of an intact acinus. A continuum mechanics model of the lung parenchyma was used for acinar tissue material model, and surface tension effects were explicitly included. An anisotropic mechanical field analysis based on a stretch tensor was combined with a curvature-based local structure analysis. FINDINGS: The airspace of the acinus exhibited nonspherical deformation as a result of the anisotropic deformation of acinar tissue. A strain hotspot occurred at the ridge-shaped region caused by a rod-like deformation of acinar tissue on the ridge. The local structure becomes bowl-shaped for inflation and, without surface tension effects, the surface of the bowl-shaped region primarily experiences isotropic deformation. Surface tension effects suppressed the increase in airspace volume and inner surface area, while facilitating anisotropic deformation on the alveolar surface. INTERPRETATION: In the lungs, the heterogeneous acinar structure and surface tension induce anisotropic deformation at the acinar and alveolar scales. Further research is needed on structural variation of acini, inter-acini connectivity, or dynamic behavior to understand multiscale lung mechanics.

The disuse effect on canal network structure and oxygen supply in the cortical bones of rats.

In this study, based on the measurements of intracortical vascular canal structure, we investigated the disuse effect on local O2 supply in the cortical bones of growing rats. Hindlimb disuse was produced by unilateral sciatic neurectomy (SN) at 4 weeks age. The canal network structures within tibial cortical bone were evaluated in 8- and 12-week-old rats undergoing SN or no treatment (control) by synchrotron radiation micro-CT. Additionally, we developed an intracortical network model by combining the imaged-based canal network with a bone matrix containing theoretical lacunar-canalicular network, and determined the distribution of O2 concentration in bone tissue numerically. In the control bone, canal network was reduced with growth, resulting in decreased blood flow and averaged O2 concentration and increased spatial heterogeneity in tissue O2 concentration. Disuse reduced the canal network, leading to a lower flow rate, lower average O2 concentration and higher heterogeneity of O2 concentrations. However, the rarefaction of the canal network with growth was smaller under the disuse condition, and accordingly, the flow rate, the average O2 concentration and the heterogeneity of O2 concentrations remained stable. In particular, although the fraction of the canal volume was smaller, the densities of canal segments and bifurcation points under disuse condition tended to be higher than those of the control bone. The heterogeneity of O2 concentration was lower. Our results indicated that the disuse may lead to more uniformity in the canal network structure and thereby uniform O2, possibly contributing to O2 supply efficiency.

Unloading of intercellular tension induces the directional translocation of PKCα.

The migration of endothelial cells (ECs) is closely associated with a Ca2+ -dependent protein, protein kinase Cα (PKCα). The disruption of intercellular adhesion by single-cell wounding has been shown to induce the directional translocation of PKCα. We hypothesized that this translocation of PKCα is induced by mechanical stress, such as unloading of intercellular tension, or by intercellular communication, such as gap junction-mediated and paracrine signaling. In the current study, we found that the disruption of intercellular adhesion induced the directional translocation of PKCα even when gap junction-mediated and paracrine signaling were inhibited. Conversely, it did not occur when the mechanosensitive channel was inhibited. In addition, the strain field of substrate attributable to the disruption of intercellular adhesion tended to be larger at the areas corresponding with PKCα translocation. Recently, we found that a direct mechanical stimulus induced the accumulation of PKCα at the stimulus area, involving Ca 2+ influx from extracellular space. These results indicated that the unloading of intercellular tension induced directional translocation of PKCα, which required Ca 2+ influx from extracellular space. The results of this study indicate the involvement of PKCα in the Ca 2+ signaling pathway in response to mechanical stress in ECs.

A combination of the finite element analysis and experimental indentation via the cornea.

The purpose of this study was to perform a set of experimental indentation test to certify our proposed eye model enables to have a better deformation assessment for the eye globe under the indentation load compared to other eye models. To do that, twenty-four enucleated human globes were removed from the cadavers. A screw at 5 different loading rates indented to the eye globes and the resulting macroscopic force-displacement as a result of the deformation in the apex of the cornea was measured. The experimental results revealed significantly higher stiffness, elastic modulus, and maximum force for the globe at higher loading rates (50 and 100 mm/min) (n = 4 globes, p < 0.05, post hoc Scheffe method) compared to the lower ones (5, 10, and 20 mm/min). The mean stiffness, elastic modulus as well as the mean maximum force of 1.64 ±â€¯0.38 N/mm, 303.40 ±â€¯111.10 kPa, and 53.88 ±â€¯17.63 N (Mean ±â€¯SD) were observed for the eye globes under all loading rates, respectively. Our eye model due to incorporating the anterior (cornea, aqueous body, and iris) and posterior (sclera, retina, and vitreous body) components showed a good agreement with force-displacement diagrams compared to that of the experimental results not only at lower but also at higher loading rates.

Impacts of Diabetes and an SGLT2 Inhibitor on the Glomerular Number and Volume in db/db Mice, as Estimated by Synchrotron Radiation Micro-CT at SPring-8.

BACKGROUND: Recent large-scale clinical studies demonstrate that sodium-glucose cotransporter 2 (SGLT2) inhibitors protect the diabetic kidney. However, clinical and animal studies have not shown the changes of the total glomeruli in the whole kidney treated with SGLT2 inhibitors. METHODS: We performed computed tomography (CT) imaging on mice using synchrotron radiation to investigate the impact of luseogliflozin, a SGLT2 inhibitor, on the number and volume of glomeruli in the whole kidney. FINDINGS: We did not observe a significant difference in the total glomerular number (Nglom) among mice. Luseogliflozin redistributed the number of glomeruli in different regions, accompanied by the normalization of diabetes-augmented renal volume (Vkidney). Diabetic db/db mice had a larger glomerular volume in the mid-cortex than did control db/m mice, and luseogliflozin increased the glomerular volume in all renal cortical zones of the whole kidney in db/db mice. According to the multivariate regression analysis, hemoglobin A1c level was the most relevant determinant of Vkidney, not Nglom or mean glomerular volume (Vglom), indicating that hyperglycemia induced renal (tubular) hypertrophy, but not glomerular enlargement. Luseogliflozin increased hypoxia in the juxtamedullary region, sustained upregulated renal renin expression and plasma renin activity, and failed to decrease albuminuria by downregulating megalin in db/db mice. INTERPRETATION: Based on our findings, SGLT2 inhibitors may alter glomerular distribution and size in addition to their glucose-lowering effects, presumably by affecting oxygen metabolism and humoral factors. FUND: Funding for this research was provided by The Japan Society for the Promotion of Science, the Japan Diabetes Foundation, and Asahikawa Medical University.

Three-dimensional model of intracellular and intercellular Ca2+ waves propagation in endothelial cells.

Intracellular and intercellular Ca2+ waves play key roles in cellular functions, and focal stimulation triggers Ca2+ wave propagation from stimulation points to neighboring cells, involving localized metabolism reactions and specific diffusion processes. Among these, inositol 1,4,5-trisphosphate (IP3) is produced at membranes and diffuses into the cytoplasm to release Ca2+ from endoplasmic reticulum (ER). In this study, we developed a three-dimensional (3D) simulation model for intercellular and intracellular Ca2+ waves in endothelial cells (ECs). 3D model of 2 cells was reconstructed from confocal microscopic images and was connected via gap junctions. Cells have membrane and cytoplasm domains, and metabolic reactions were divided into each domain. Finally, the intracellular and intercellular Ca2+ wave propagations were induced using microscopic stimulation and were compared between numerical simulations and experiments. The experiments showed that initial sharp increases in intracellular Ca2+ occurred approximately 0.3 s after application of stimuli. In addition, Ca2+ wave speeds remained constant in cells, with intracellular and intercellular speeds of approximately 35 and 15 µm/s, respectively. Simulations indicated initial increases in Ca2+ concentrations at points of stimulation, and these were then propagated across stimulated and neighboring cells. In particular, initial rapid increases in intracellular Ca2+ were delayed and subsequent intracellular and intercellular Ca2+ wave speeds were approximately 25 and 12 µm/s, respectively. Simulation results were in agreement with those from cell culture experiments, indicating the utility of our 3D model for investigations of intracellular and intercellular messaging in ECs.

A comparative study to determine the optimal intravitreal injection angle to the eye: A computational fluid-structure interaction model.

This study was aimed at investigating the role of IVI angle on the induced stresses and deformations among the components of the eye. Thereafter, the most optimal angle of IVI to minimize the complications of post IVI at the injection site on a basis of the computed stresses via a Fluid-Structure Interaction (FSI) computational model was proposed. IntraVitreal Injection (IVI) is broadly employed as a principal treatment of vascular vitro-retinal diseases. So far, there have been reports regarding the complications of post IVI and determine them as severe uveitis, tractional retinal detachment, IntraOcular Pressure (IOP) elevation as well as ocular haemorrhage. However, there is a lack of knowledge on how to reduce the subsequent ocular tissue damage and patient symptoms in the injection site. Seven different IVI angles were simulated, including 0∘, 15∘, 30∘, 45∘, 60∘, 75∘, and 90∘, through the Finite Element (FE) code; and the term, 'post IVI complication' or 'injury', in the results was interpreted as the level of maximal principal stress in the eye components. The results revealed the lowest amount of stresses at the angle of 45∘ in respect to the horizontal line (acute to the surface of the sclera) for the lens, iris, vitreous body, aqueous body, ciliary body, sclera, retina, and choroid. The cornea illustrated the same amount of stress at the angles of 45∘, 60∘, 75∘, and 90∘ with the highest one at the IVI angle of 30∘. The lowest and the highest stresses among the eye components regardless of IVI angle were observed in the choroid and retina/sclera, respectively, which imply the importance of the IVI angle on the stresses of these eye components. The findings of the contemporary research revealed that the IVI angle of 45∘ would trigger less post IVI complications and, as a result, a more effective surgery outcome compared to the other angles, i.e., 0∘, 15∘, 30∘, 60∘, 75∘, and 90∘.