MiR-125b attenuates retinal pigment epithelium oxidative damage via targeting Nrf2/HIF-1α signal pathway.

The retinal pigment epithelium cells (RPE) are sensitive to oxidative stimuli due to long-term exposure to various environmental stimuli. Thus, the oxidative injury of RPE cells caused by the imbalance of redox homeostasis is one of the main pathogenic factors of age-related macular degeneration (AMD). But the sophisticated mechanisms linking AMD to oxidative stress are not fully elucidated. Activation of Nrf2 signal pathway can protect RPE cells from oxidative damage. The present study investigated the regulating mechanism of miR-125b in Nrf2 cascade and evaluated its antioxidant capacity. The in vitro studies indicated that overexpression of miR-125b substantially inhibited Keap1 expression, enhanced Nrf2 expression and induced Nrf2 nuclear translocation. Importantly, functional studies demonstrated that forced expression of miR-125b could significantly elevate cell proliferation and superoxide dismutase (SOD) levels while reduce reactive oxygen species (ROS) overproduction and malondialdehyde (MDA) formation. Further studies showed that miR-125b had no effect when Nrf2 was silenced in ARPE-19 cells. Additionally, the results identified that Nrf2 silence induced ROS accumulation enhances HIF-1α protein expression, while miR-125b could offset this effect via promoting HIF-1α protein degradation. Subsequent in vivo studies demonstrated that sodium iodate induced outer retina thinner was reversed with exogenous supplementation of miR-125b, which was cancelled in Nrf2 knockout mice. In conclusion, this study illustrated that miR-125b can protect RPE from oxidative damage via targeting Nrf2/HIF-1α signal pathway and potentially may serve as a therapeutic agent of AMD.

Human lens epithelial cell apoptosis and epithelial to mesenchymal transition in femtosecond laser-assisted cataract surgery.

AIM: To evaluate human lens epithelium cell apoptosis and epithelial to mesenchymal transition (EMT) induced by femtosecond laser in femtosecond laser assisted cataract surgery (FLACS). METHODS: Sixty cataract patients with N2 to N3 stage according to the LOCS III were enrolled in this study and divided into three groups randomly: FLACS1 group (cataract surgery by FLACS with LenSx), FLACS2 group (cataract surgery by FLACS with LensAR) and manual group (cataract surgery by phacoemulsification). Patients in two FLACS groups performed anterior capsulotomy by LenSx or LensAR laser system. Patients in the manual group were performed continuous curvilinear capsulorrhexis (CCC) manually. The anterior capsules were fixed right after moved out of eye. Hematoxylin-eosine staining, immunofluorescence staining and real-time PCR were performed in order to observe human lens epithelium cells changes after cataract surgery. RESULTS: The capsule cutting edge was shown irregularity and roughness in two FLACS groups and smooth edge in manual capsulotomy by pathologic staining. Irregularities of the cell configuration with partly swollen and destroyed nuclei were observed in two FLACS groups. Femtosecond laser could induce a significantly higher cell apoptosis in human lens epithelium cell than manually performed CCC (P<0.05). Lens epithelium cells apoptosis were correlated with femtosecond laser duration according to Pearson correlation analysis. Decreased N-cadherin expression, alpha-SMA and FSP-1 level in two FLACS groups showed the inhibition of cell EMT. CONCLUSION: Femtosecond laser may affect the apoptosis and EMT of lens epithelium cells which are under the peeled central lens capsule.

Optimal incision sites to reduce corneal aberration variations after small incision phacoemulsification cataract surgery.

AIM: To analyze the effect of steep meridian small incision phacoemulsification cataract surgery on anterior, posterior and total corneal wavefront aberration. METHODS: Steep meridian small incision phacoemulsification cataract surgery was performed in age-related cataract patients which were divided into three groups according to the incision site: 12 o'clock, 9 o'clock and between 9 and 12 o'clock (BENT) incision groups. The preoperative and 3-month postoperative root mean square (RMS) values of anterior, posterior and total corneal wavefront aberration including coma, spherical aberration, and total higher-order aberrations (HOAs), were measured by Pentacam scheimpflug imaging. The mean preoperative and postoperative corneal wavefront aberrations were documented. RESULTS: Total corneal aberration and total lower-order aberrations decreased significantly in three groups after operation. RMS value of total HOAs decreased significantly postoperatively in the 12 o'clock incision group (P<0.001). Corneal spherical aberration was statistically significantly lower after steep meridian small incision phacoemulsification cataract surgery in BENT incision group (P<0.05) and Pearson correlation analysis indicated that spherical aberration changes had no significant relationship with total astigmatism changes in all three corneal incision location. CONCLUSION: Corneal incision of phacoemulsification cataract surgery can affect corneal wavefront aberration. The 12 o'clock corneal incision eliminated more HOAs and the spherical aberrations decreased in BENT incision group obviously when we selected steep meridian small incision. Cataract lens replacement using wavefront-corrected intraocular lens combined with optimized corneal incision site would improve ocular aberration results.

Confocal microscopic evaluation of cornea after AquaLase liquefaction cataract extraction.

AIM: The most recent and innovative AquaLase liquefaction technology has offered an alternative to lens extraction. Many studies have investigated its functions and advantages. This article focuses on evaluating the in vivo microscopic cornea changes after AquaLase liquefaction by using a laser confocal microscope. METHODS: In this perspective, randomized case study, 37 eyes of 35 patients submitted to cataract surgery were chosen to undergo AquaLase liquefaction cataract extraction. Each patient was assessed before the operation, on the 1(st), 7(th), and 30(th) postoperative days, and 6 months after the cataract extraction. The morphologies and quantitative comparisons of corneal cells and corneal nerves layer by layer were evaluated in vivo with the Heidelberg Retina Tomograph III-Rostock Cornea Module (HRT-III RCM) confocal microscope. ANOVA and Post-Hoc Bonferroni test were carried out to compare the results pre- and post-operation. RESULTS: ANOVA results indicated no post-operation changes for epithelium and anterior stroma cells. Irregular segments of sub-basal nerve fiber were most pronounced seven days post-operation. In the mid and posterior stroma, keratocytes were obvious compared with the preoperative condition. Corneal endothelium cells became obviously swollen in cytoplasm and nucleus. The mid and posterior stroma cell density decreased from the 1(st) to 7(th) postoperative days (P<0.05). The corneal endothelium cell density decreased (P<0.05) and did not revert to the preoperative level after six months (P<0.05). CONCLUSION: Slight microstructural abnormalities were identified in the corneal recovery process after AquaLase liquefaction. AquaLase liquefaction cataract extraction is safe for cornea.