Semaphorin 7a participants in pterygium by regulating vascular endothelial growth factor.

AIM: To investigate the relationship between semaphorin 7a expression and cell proliferation and migration in pterygium fibroblasts. METHODS: Twenty-six patients with surgically diagnosed pterygium were enrolled, including 15 cases of primary pterygium and 11 cases of recurrent pterygium. In addition, 12 cases of normal conjunctival tissue were collected. The expression of semaphorin 7a in normal conjunctival tissue, primary pterygium and recurrent pterygium was detected by real-time polymerase chain reaction. Recurrent pterygium fibroblasts were isolated and cultured, and the expression of semaphorin 7a was silenced by small interfering RNA (siRNA) interference technique. Furthermore, the effects of si-semaphorin 7a interference on the mRNA and protein levels of ß1-integrin, vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor receptor (VEGFR), and on fibroblast proliferation were analyzed. Transwell assay was used to detect the effect of semaphorin 7a interference on fibroblast migration. RESULTS: Semaphorin 7a was highly expressed in the primary pterygium and recurrent pterygium samples than that of the normal conjunctival tissue. Compared with the primary pterygium, the expression of semaphoring 7a in the recurrent pterygium samples was significantly increased (P<0.05). The mRNA and protein expression levels of ß1-integrin, VEGFA and VEGFR were decreased after si-semaphorin 7a transfection, and as well as the cell proliferation and migration. CONCLUSION: Semaphorin 7a might play important roles in the pathogenesis of pterygium by affecting the expression of ß1-integrin, VEGFA and VEGFR.

Therapeutic and inducing effect of corneal crosslinking on infectious keratitis.

The corneal crosslinking (CXL) with riboflavin and ultraviolet-A (UVA) is a new therapy method to successfully treat infectious keratitis in clinical practice. However, there are rare reports on the complications of CXL such as the secondary keratitis. The diverse clinical outcomes on keratitis have highlighted the necessity to further evaluate the efficacy and complications of CXL. We reviewed the positive and negative reports on UVA/riboflavin related with keratitis and provided our opinion on the therapeutic and side effect of UVA/riboflavin crosslinking on keratitis.

Corrigendum to "A Review of Collagen Cross-Linking in Cornea and Sclera".

[This corrects the article DOI: 10.1155/2015/289467.].

Combining corneal crosslinking and phakic toric Implantable Collamer Lenses for the treatment of keratectasia: A case report.

The present study reports the use of a phakic toric Implantable Collamer Lens (ICL) that improved the refraction correction of high myopia and astigmatism in a case of keratectasia following corneal cross-linking. A 31-year-old male was diagnosed with keratectasia 12 years after laser-assisted in situ keratomileusis (LASIK). Following LASIK, the manifest refraction was -3.50-2.25×90 [0.1 logarithmic expression (LogMAR) best corrected visual acuity (BVCA)] in the right eye and -8.00-3.50×175 (0.3 LogMAR BCVA) in the left eye, with a LogMAR uncorrected distance visual acuity (UDVA) of 0.8 and a 'counting fingers' value of 3 ft (CF @3 ft) in the left and right eyes, respectively. Riboflavin/ultraviolet A light (UVA) corneal crosslinking (CXL) was conducted on both eyes. Seven months after cross-linking, LogMAR UDVA was 0.4, the manifest refraction was -2.75-2.50×85 and LogMAR BCVA was 0.1 in the right eye. In the left eye, LogMAR UDVA was CF @3 ft, the manifest refraction was -15.00 and LogMAR BCVA was 0.3. The corneal topography was stable 7 months after CXL. Phakic toric ICL was implanted to correct the refractive error, following which the LogMAR UDVA improved to 0.1 in the right eye and 0.3 in left eye, and visual acuity remained stable for 6 months after ICL implantation. In conclusion, combining riboflavin/UVA corneal cross-linking and phakic toric ICL implantation may be an alternative in the correction of high refractive error in patients with keratectasia.

Augmented anti-angiogenesis activity of polysulfated heparin-endostatin and polyethylene glycol-endostatin in alkali burn-induced corneal ulcers in rabbits.

Endostatin (ES) is an endogenous angiogenesis inhibitor that has the ability to inhibit tumor growth and metastasis. However, its clinical application is limited by a number of disadvantages, such as poor stability, short half-life and the requirement of high doses to maintain its efficacy. The chemical modification on ES may offer a solution to these disadvantages. The aim of the present study was to evaluate the effects of ES, polysulfated heparin-endostatin (PSH-ES) and polyethylene glycol-endostatin (PEG-ES) on the endothelial cell proliferation and angiogenesis associated with corneal neovascularization (CNV) and to determine their mechanisms of action. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) was used to study the effects of ES and its derivatives on endothelial cell proliferation in vitro, and rabbits were used to evaluate the effects of ES and its derivatives on CNV in vivo. In the evaluation of CNV, the expression of vascular endothelial growth factor in the cornea was measured via immunohistochemistry and microvessels were counted. ES and its derivatives significantly inhibited endothelial cell proliferation in vitro (P<0.05) and suppressed CNV in vivo. Among the compounds examined, ES most effectively inhibited endothelial cell proliferation in vitro (P<0.05); however, PSH-ES and PEG-ES most effectively inhibited CNV in vivo (P<0.05). These results indicate that PSH-ES and PEG-ES are candidate anti-angiogenesis drugs.

Inhibitory effect of polysulfated heparin endostatin on alkali burn induced corneal neovascularization in rabbits.

AIM: To investigate anti-angiogenic effects of polysulfated heparin endostatin (PSH-ES) on alkali burn induced corneal neovascularization (NV) in rabbits. METHODS: An alkali burn was made on rabbit corneas to induce corneal NV in the right eye of 24 rabbits. One day after burn creation, a 0.2 mL subconjunctival injection of 50 µg/mL PSH-ES, 50 µg/mL recombinant endostatin (ES), or normal saline was administered every other day for a total of 14d (7 injections). Histology and immunohistochemisty were used to examine corneas. Corneal NV growth was evaluated as microvessel quantity and corneal vascular endothelial growth factor (VEGF) expression was measured by immunohistochemical assay. RESULTS: Subconjunctival injection of ES and PSH-ES resulted in significant corneal NV suppression, but PSH-ES had a more powerful anti-angiogenic effect than ES. Mean VEGF concentration in PSH-ES treated corneas was significantly lower than in ES treated and saline treated corneas. Histological examination showed that corneas treated with either PSH-ES or ES had significantly fewer microvessels than eyes treated with saline. Additionally corneas treated with PSH-ES had significantly fewer microvessels than corneas treated with ES. CONCLUSION: Both PSH-ES and recombinant ES effectively inhibit corneal NV induced by alkali burn. However, PSH-ES is a more powerful anti-angiogenic agent than ES. This research has the potential to provide a new treatment option for preventing and treating corneal NV.

A review of collagen cross-linking in cornea and sclera.

Riboflavin/UVA cross-linking is a technique introduced in the past decades for the treatment of keratoconus, keratectasia, and infectious keratitis. Its efficacy and safety have been investigated with clinical and laboratory studies since its first clinical application by Wollensak for the treatment of keratoconus. Although its complications are encountered during clinical practice, such as infection inducing risk, minimal invasion merits a further investigation on its future application in clinical practice. Recently, collagen cross-linking in sclera shows a promising prospect. In present study, we summarized the representative studies describing the clinical and laboratory application of collagen cross-linking published in past decades and provided our opinion on the positive and negative results of cross-linking in the treatment of ophthalmic disorders.

A short-term study of corneal collagen cross-linking with hypo-osmolar riboflavin solution in keratoconic corneas.

AIM: To report the 3mo outcomes of collagen cross-linking (CXL) with a hypo-osmolar riboflavin in thin corneas with the thinnest thickness less than 400 µm without epithelium. METHODS: Eight eyes in 6 patients with age 26.2±4.8y were included in the study. All patients underwent CXL using a hypo-osmolar riboflavin solution after its de-epithelization. Best corrected visual acuity, manifest refraction, the thinnest corneal thickness, and endothelial cell density were evaluated before and 3mo after the procedure. RESULTS: The mean thinnest thickness of the cornea was 408.5±29.0 µm before treatment and reduced to 369.8±24.8 µm after the removal of epithelium. With the application of the hypo-osmolar riboflavin solution, the thickness increased to 445.0±26.5 µm before CXL and recover to 412.5±22.7 µm at 3mo after treatment, P=0.659). Before surgery, the mean K-value of the apex of the keratoconus corneas was 57.6±4.0 diopters, and slightly decreased (54.7±4.9 diopters) after surgery (P=0.085). Mean best-corrected visual acuity was 0.55±0.23 logarithm of the minimal angle of resolution, and increased to 0.53±0.26 logarithm after surgery (P=0.879). The endothelial cell density was 2706.4±201.6 cells/mm(2) before treatment, and slightly decreased (2641.2±218.2 cells/mm(2)) at last fellow up (P=0.002). CONCLUSION: Corneal collagen cross-linking with a hypo-osmolar riboflavin in thin corneas seems to be a promising treatment. Further study should be done to evaluate the safety and efficiency of CXL in thin corneas for the long-term.

Evaluation of the in vitro antimicrobial properties of ultraviolet A/riboflavin mediated crosslinking on Candida albicans and Fusarium solani.

AIM: To evaluate the antimicrobial properties of ultraviolet A (UVA) (365 nm)/riboflavin against Candida albicans and Fusarium solani. METHODS: Two fungus isolates were cultured in vitro and prepared with 10-fold serial PBS dilutions of cell concentration. For each dilution of fungus suspension, the concentration (colony-forming units/mL, CFU/mL) and the inactivation ratio of fungal cells were evaluated under 4 conditions: no treatment (control), UVA (365 nm)/riboflavin, riboflavin, and UVA (365 nm). RESULTS: The cell concentration decreased in UVA (365 nm)/riboflavin group for Candida albicans at each dilution and Fusarium solani at dilutions of 10(4), 10(3), 10(2) CFU/mL, when compared with that in control, riboflavin, and UVA (365 nm) groups (P<0.01). No difference of cell concentration was detected amongst the culture of control, riboflavin, and UVA (365 nm) groups for the two fungus. There is a negative correlation between suspension concentration (log-transformed) and the inactivation ratio in UVA (365 nm)/riboflavin group for Candida albicans and Fusarium solani (P<0.01). CONCLUSION: According to the standard protocol of corneal collagen cross-linking, UVA (365 nm)/riboflavin combination treatment is found to moderately inactivate the viability of Candida albicans and Fusarium solani in vitro. The inactivation ratio was found to increase with the decrease of cell concentration under UVA (365 nm)/riboflavin condition.

Comparative study of visual acuity and aberrations after intralase femtosecond LASIK: small corneal flap versus big corneal flap.

AIM: To study the effect of different flap sizes on visual acuity, refractive outcomes, and aberrations after femtosecond laser for laser in situ keratomileusis (LASIK). METHODS: In each of the forty patients enrolled, 1 eye was randomly assigned to receive treatment with a 8.1mm diameter corneal flap, defined as the small flap, while the other eye was treated with a 8.6mm diameter corneal flap, defined as the big flap. Refractive errors, visual acuity, and higher-order aberrations were compared between the two groups at week 1, month 1 and 3 postoperatively. RESULTS: The postoperative refractive errors and visual acuity all conformed to the intended goal. Postoperative higher-order aberrations were increased, especially in spherical aberration (Z12) and vertical coma (Z7). There were no statistically significant differences between the two groups in terms of postoperative refractive errors, visual acuity, root mean square of total HOAs (HO-RMS), trefoil 30° (Z6), vertical coma (Z7), horizontal coma (Z8), trefoil 0° (Z9), and spherical aberration (Z12) at any point during the postoperative follow-up. CONCLUSION: Both the small and big flaps are safe and effective procedures to correct myopia, provided the exposure stroma meets the excimer laser ablations. The personalized size corneal flap is feasible, as we can design the size of corneal flap based on the principle that the corneal flap diameter should be equal to or greater than the sum of the maximum ablation diameter and apparatus error.

Vitamin K2 inhibits the growth of hepatocellular carcinoma via decrease of des-gamma-carboxy prothrombin.

BACKGROUND: Des-gamma-carboxy prothrombin (DCP) is a serum protein produced by hepatocellular carcinoma (HCC) cells in the absence of vitamin K. Serum and tissue DCP expressions are thought to reflect the biological malignant potential of HCC. Hence, we aimed to examine the efficacy of vitamin K(2) on the production of DCP as well as tumor cell growth and invasion. METHODS: Cell growth and viability were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. The in vivo efficacy of vitamin K(2) was examined in nude mice bearing HCC cells. A 24-well transwell chamber was used to evaluate the motility and invasive ability of HCC cells. Levels of DCP in supernatant of cultures and in serum of mice were measured using an electrochemiluminescence immunoassay method. Western blot and immunohistochemical analysis were employed to evaluate the expression of DCP in HCC. RESULTS: Vitamin K(2) (2-40 muM) significantly decreased the levels of DCP production in supernatant of PLC/PRF/5 and HepG2 cells and in serum of nude mice bearing HCC xenografts. The inhibition of DCP was also observed using the assays of Western blot analysis in HCC cultures and immunohistochemical analysis in HCC xenografts in mice. As a result of administration of vitamin K(2), the capacity of HCC growth was inhibited and the invasion and migration of tumor cells were decreased. Furthermore, the inhibitory effects of HCC growth were also observed in vivo and the sensitivity was well correlated with the decrease of DCP in the serum of mice. CONCLUSION: Vitamin K(2) might suppress the growth and invasion of HCC cells via decrease of DCP.