Glaucoma is the primary cause of irreversible blindness worldwide associated with high intraocular pressure (IOP). Elevated intraocular pressure will affect the normal aqueous humor outflow, resulting in deformation of iris. However, the deformation ability of iris is closely related to its material properties. Meanwhile, the passive deformation of the iris aggravates the pupillary block and angle closure. The nature of the interaction mechanism of iris deformation and aqueous humor fluid flow has not been fully understood and has been somewhat a controversial issue. The purpose here was to study the effect of IOP, localization, and temperature on the flow of the aqueous humor and the deformation of iris interacted by aqueous humor fluid flow. Based on mechanisms of aqueous physiology and fluid dynamics, 3D model of anterior chamber (AC) was constructed with the human anatomical parameters as a reference. A 3D idealized standard geometry of anterior segment of human eye was performed. Enlarge the size of the idealization geometry model 5 times to create a simulation device by using 3D printing technology. In this paper, particle image velocimetry technology is applied to measure the characteristic of fluid outflow in different inlet velocity based on the device. Numerically calculations were made by using ANSYS 14.0 Finite Element Analysis. Compare of the velocity distributions to confirm the validity of the model. The fluid structure interaction (FSI) analysis was carried out in the valid geometry model to study the aqueous flow and iris change. In this paper, the validity of the model is verified through computation and comparison. The results indicated that changes of gravity direction of model significantly affected the fluid dynamics parameters and the temperature distribution in anterior chamber. Increased pressure and the vertical position increase the velocity of the aqueous humor fluid flow, with the value increased of 0.015 and 0.035 mm/s. The results act on the iris showed that, gravity direction from horizontal to vertical decrease the equivalent stress in the normal IOP model, while almost invariably in the high IOP model. With the increased of the iris elasticity modulus, the equivalent strain and the total deformation of iris is decreased. The maximal value of equivalent strain of iris in high IOP model is higher than that of in normal IOP model. The maximum deformation of iris is lower in the high IOP model than in the normal IOP model. The valid model of idealization geometry of human eye could be helpful to study the relationship between localization, iris deformation and IOP. So far the FSI analysis was carried out in that idealization geometry model of anterior segment to study aqueous flow and iris change.
6 September 2021 in Frontiers in Molecular Biosciences
High intraocular pressure (IOP) is a major risk factor for glaucoma, a leading cause of irreversible blindness. Abnormal fibrotic activity in the human trabecular meshwork (HTM) cells is considered to be partly responsible for the increased resistance of aqueous humor outflow and IOP. This study aimed to identify the fibrotic pathways using integrated bioinformatics and further elucidate their mechanism of regulating fibrotic activity in dexamethasone (DEX)-treated HTM cells. Microarray datasets from the GEO database were obtained and analyzed by GEO2R. Bioinformatics analyses, including GO and KEGG analyses, were performed to explore biological functions and signaling pathways of differentially expressed genes (DEGs). The fibrotic pathways and targets were determined by western blot, RT-qPCR, or immunofluorescence staining. The cellular elastic modulus was measured using an atomic force microscope. A total of 204 DEGs, partly enriched in fibrotic activity (collagen-containing ECM, fibroblast activation) and Rap1, Ras, TGF-β, and Hippo pathways, were identified. Experimental results showed that DEX induced fibrotic activity and regulated the expression of RhoA/ROCK in HTM cells. Similarly, the constitutively active RhoA (RhoAG14V) also promoted the fibrotic activity of HTM cells. Mechanistically, RhoAG14V induced the expression and nuclear translocation of YAP/TAZ to produce CTGF. Moreover, inhibition of ROCK or YAP decreased the expression of Collagen I and α-SMA proteins induced by DEX or RhoAG14V in HTM cells. In conclusion, these results indicate that RhoA/ROCK-YAP/TAZ axis plays a crucial role in regulating the fibrotic activity of DEX-treated HTM cells.
Understanding the mechanical properties of the iris can help to have an insight into the eye diseases with abnormalities of the iris morphology. Material parameters of the iris were simply calculated relying on the ex vivo experiment. However, the mechanical response of the iris in vivo is different from that ex vivo, therefore, a method was put forward to determine the material parameters of the iris using the optimization method in combination with the finite element method based on the in vivo experiment. Ocular hypertension was induced by rapid perfusion to the anterior chamber, during perfusion intraocular pressures in the anterior and posterior chamber were record by sensors, images of the anterior segment were captured by the ultrasonic system. The displacement of the characteristic points on the surface of the iris was calculated. A finite element model of the anterior chamber was developed using the ultrasonic image before perfusion, the multi-island genetic algorithm was employed to determine the material parameters of the iris by minimizing the difference between the finite element simulation and the experimental measurements. Material parameters of the iris in vivo were identified as the iris was taken as a nearly incompressible second-order Ogden solid. Values of the parameters μ1, α1, μ2 and α2 were 0.0861 ± 0.0080 MPa, 54.2546 ± 12.7180, 0.0754 ± 0.0200 MPa, and 48.0716 ± 15.7796 respectively. The stability of the inverse finite element method was verified, the sensitivity of the model parameters was investigated. Material properties of the iris in vivo could be determined using the multi-island genetic algorithm coupled with the finite element method based on the experiment.
The tilt and decentration of intraocular lens (IOL) result in defocussing, astigmatism, and wavefront aberration after operation. The objective is to give a method to estimate the tilt and decentration of IOL more accurately. Based on AS-OCT images of twelve eyes from eight cases with subluxation lens after operation, we fitted spherical equation to the data obtained from the images of the anterior and posterior surfaces of the IOL. By the established relationship between IOL tilt (decentration) and the scanned angle, at which a piece of AS-OCT image was taken by the instrument, the IOL tilt and decentration were calculated. IOL tilt angle and decentration of each subject were given. Moreover, the horizontal and vertical tilt was also obtained. Accordingly, the possible errors of IOL tilt and decentration existed in the method employed by AS-OCT instrument. Based on 6–12 pieces of AS-OCT images at different directions, the tilt angle and decentration values were shown, respectively. The method of the surface fitting to the IOL surface can accurately analyze the IOL’s location, and six pieces of AS-OCT images at three pairs symmetrical directions are enough to get tilt angle and decentration value of IOL more precisely.