Tumor Suppressor miR-184 Enhances Chemosensitivity by Directly Inhibiting SLC7A5 in Retinoblastoma.

The expression patterns and functional roles of miRNAs in retinoblastoma (RB) are poorly understood, especially those involved in chemoresistance. Here, we validated the expression pattern of 20 potential RB-suppressive miRNAs and confirmed that miR-184 is the most significantly decreased miRNA in human RB tissues, as well as chemoresistant cell line. Bioinformatic and molecular analyses revealed that SLC7A5 has three binding sites of miR-184 and significantly increased in RB tissues. miR-184 negatively correlated with SLC7A5 expression in RB tissues and mainly target position 2494-2513 of the SLC7A5 3'UTR to inhibit its expression. Furthermore, enforced expression of miR-184 reversed the oncogenic roles of SLC7A5 on proliferation, migration, and invasion of RB cells. In addition, miR-184 also enhances chemosensitivity of RB cells via inducing apoptosis and G2/M cell cycle arrest. Molecular studies revealed that miR-184-decreased phosphorylation status of known DNA damage repair sensors of the ATR/ATM pathways and induced persistent formation of γH2AX foci depend on targeting SLC7A5, leading to persistent DNA damage. Thus, targeting the miR-184/SLC7A5 pathway will provide new opportunities for drug development to reverse chemotherapeutic resistance in RB.

[Role of endothelial progenitor cells in optic nerve injury of rats].

OBJECTIVE: To investigate the role of endothelial progenitor cells (EPC) in the injury of rat optic nerve. METHODS: An experimental study. The rat model of optic nerve injury was created by fluid percussion brain injury device (FPI). On hundred and eight rats (108 eyes) were divided into 2 groups randomly. Each group was further divided into 9 subgroups by the time of injury (24 h before and 3, 12, 24, 48, 72 h, 1, 2 and 3 weeks after the injury). The number of circulating EPCs was measured, HE staining of the optic nerve, immunohistochemistry study of CD31 (markers of vascular endothelial cells) and flash-visual evoked potential (F-VEP) were observed at every time point. Two independent sample t-test was used for the comparison between the control group and the optic nerve injury groups at the same time point. The correlation between different items was analyzed by Pearson test. P value less than 0.05 was considered significant. RESULTS: The number of EPCs in normal rats was 46-52/200 000 monocytes. After traumatic optic nerve injury, the number of EPCs was (34 ± 4, 34 ± 5, 69 ± 9, 76 ± 6, 107 ± 9, 69 ± 7, 58 ± 6 and 56 ± 4)/200 000 monocytes at 3, 12, 24, 48, 72 h, and 1, 2 and 3 weeks. The difference of number of EPCs between the experiment and control groups was significant at 3, 12, 24, 48, 72 h and 1 and 2 weeks after the injury (t = 5.29, 2.90, -4.30, -7.61, -14.17, -5.74 and -2.79; P < 0.05). The number of CD31(+) cell in the optic nerve and surround tissues in normal rats was (7-9)/5 high magnification field. After the injury, the number of CD31(+) cell was 8.36 ± 1.52, 7.17 ± 1.10, 10.41 ± 1.92, 11.43 ± 1.58, 14.29 ± 2.03, 17.33 ± 1.47, 17.86 ± 1.22 and 18.13 ± 1.40 at different time points. The difference of number of CD31(+) cell between the experiment and control groups was significant at 48, 72 h, and 1, 2, and 3 weeks after the injury (t = 4.31, -7.61, -8.17, -10.08, and -10.79; P < 0.05). The number of microvessels in the optic nerve and surround tissues in normal rats was 6-9/5 high magnification field. After traumatic optic nerve injury, the number of microvessels was 7.54 ± 2.01, 8.52 ± 2.21, 11.02 ± 1.62, 15.40 ± 2.04, 18.39 ± 1.96, 23.21 ± 1.50, 22.78 ± 2.40 and 24.13 ± 2.51 at different time points. The difference of number of microvessels between the experiment and control groups was significant at 48, 72 h, 1, 2, and 3 weeks after the injury (t = 4.25, -7.74, -8.26, -10.28 and -11.49; P < 0.05). The latency period of P waves was decreased at 3 h and increased to above basic level at 24 h, and then tend to be stable. The difference of latency period of P waves between the experiment and control groups was significant at 3, 12, 24, 48, 72 h, 1, 2 and 3 weeks after the injury (t = 4.15, 3.74, 5.84, 6.08, 6.40, 6.52, 6.53 and 6.61; P < 0.05). The amplitude of F-VEP was decreased at 3 h and increased to the basic level at 12 h, then decreased to below the basic level gradually. The difference of the amplitude of F-VEP between the experiment and control groups was significant at 3, 24, 48, 72 h, 1, 2 and 3 weeks after the injury (t = 3.95, 4.14, 5.26, 5.78, 6.49, 6.72 and 6.23; P < 0.05). The number of EPCs was correlated with the number of CD31(+) cell, microvessels and F-VEP (r = 0.43, 0.41 and 0.43; P < 0.01). CONCLUSIONS: The present study showed that the number of EPCs in the blood increases significantly after traumatic optic nerve injury, and the cells can arrive the traumatic area to repair injured tissue and enhance angiogenesis.

[Clinical study of ultrathin flap LASIK and LASEK for the treatment of high myopia with thin cornea].

OBJECTIVE: To explore the efficacy and safety of the ultrathin flap LASIK and LASEK for the treatment of high myopia with central corneal thickness below 500 microm. METHODS: Ultrathin flap LASIK and LASEK were randomly selected to treat high myopic patients with corneal thickness between 450 and 500 microm. 39 cases of 23 patients with average spherical equivalent of -7.51D (range from -6.00 to -9.50D) were treated with ultra thin flap LASIK, and 37 cases of 19 patients with average SE of -7.50D (range from -6.00 to -10.75D) were treated with LASEK. The uncorrected visual acuity, best corrected visual acuity, spherical equivalent, intraocular pressure, haze were examined and recorded 1, 3, 6 and 12 months postoperatively. RESULTS: Postoperative reaction was mild in LASIK patients, who showed a quick recovery in UCVA, whereas LASEK patients needed average 4 days to re-epithelization. At 1, 3, 6, 12 months postoperatively, the percentage of UCVA above 1.0 was 64.1%, 87.2%, 87.2% and 79.3% in LASIK patients and 37.8%, 75.7%, 67.6% and 71.4% in LASEK patients respectively. The percentage of spherical equivalent between +/- 0.50D was 48.7%, 51.3%, 61.5%, 82.8% in LASIK patients and 51.4%, 45.9%, 45.9%, 57.1% in LASEK respectively. There was no severe complications that implicate the BSCVA occurred in-operation and postoperatively. The main complications in LASIK group was corneal flap striae and overcorrection, regression and mild haze in LASEK group. CONCLUSION: Ultrathin flap LASIK had the similar efficacy and safety with LASEK in the treatment of high myopia with thin CCT, but the stability of results and satisfaction from the patients was superior to LASEK.

[Comparison of laser subepithelial keratomileusis and photorefractive keratectomy for the correction of myopia].

OBJECTIVE: To compare the effectiveness and difference between laser subepithelial keratomileusis (LASEK) and conventional photorefractive keratectomy (PRK) for the treatment of myopia up to -8.00 diopter. METHODS: In this prospective study, 46 patients with a manifest refactiion of -1.75 to -8.00 diopters were treated and followed up for 6 months. In each case, PRK was performed in one eye and LASEK in the other eye. The first eye treated and surgical method used in the first eye was randomized. Epithelial healing time, postoperative pain, uncorrected visual acuity (UCVA), manifest refraction, corneal HAZE were followed and compared in PRK and LASEK treated eyes. RESULTS: LASEK eyes took a mean time of 3.49 days to heal the epithelium, whereas PRK eyes took 2.45 days, which is statistically significant (P <0.05). Postoperative pain index was 2.04 and 2.45 in LASEK eyes and PRK eyes respectively (P <0.05). There were no significant differences between eyes in UCVA and manifest refraction during the follow time (P >0.05). However, LASEK-treated eyes showed less corneal haze than PRK eyes. CONCLUSIONS: LASEK can effectively and safely treat myopia up to -8.00 diopters as PRK did, and can diminish early pain after surgery and prevent corneal Haze from happening.