Anti-inflammatory and anti-apoptotic effects of N-acetylcysteine in diabetic rat corneal epithelium

AIM:To characterize the anti-inflammatory and antiapoptotic effects of N-acetylcysteine(NAC)in streptozotocin(STZ)-induced diabetic rat corneal epithelium and human corneal epithelial cells(HCECs)exposed to a high-glucose environment.METHODS:HCECs were incubated in 0,5,50 mmol/L glucose medium,or 50 mmol/L glucose medium with NAC for 24h.Diabetes was induced in rats by intraperitoneal injection of 65 mg/kg STZ and some of these rats were topically administered NAC to corneas with 3 mice per group.We characterized receptor for advanced glycation end-products(RAGE)expression using immunofluorescence,and interleukin(IL)-1βand cleaved caspase-3(CCAP-3)expression using immunohistochemistry.Circulating tumor necrosis factor(TNF)-αconcentration was measured by ELISA and cleaved poly-ADP ribose polymerase(PARP)concentration was quantified by Western blotting.Apoptotic cells were detected using TUNEL assay and annexin V and propidium iodide staining.RESULTS:Diabetic rats had higher expression of RAGE(2.46±0.13 fold),IL-1β,and CCAP-3 in apoptotic cells of their corneas than control rats.The expression of RAGE(1.83±0.11 fold),IL-1β,and CCAP-3,and the number of apoptotic cells,were reduced by topical NAC treatment.HCECs incubated in 50 mmol/L glucose medium showed high concentrations of TNF-α(310±2.00 pg/mL)and cleaved PARP(7.43±0.56 fold),and more extensive apoptosis than cells in 50 mmol/L glucose medium.However,the addition of NAC reduced the concentrations of TNF-α(153.67±2.31 pg/mL)and cleaved PARP(5.55±0.31 fold)and the number of apoptotic cells.CONCLUSION:NAC inhibits inflammation and apoptosis in the corneas of diabetic rats and HCECs maintained in a high-glucose environment.

Diffractive multifocal intraocular lens implantation in patients with monofocal intraocular lens in the contralateral eye

AIM:To evaluate clinical outcomes of unilateral implantation of a diffractive multifocal intraocular lens(IOL)in patients with contralateral monofocal IOL.METHODS:Twenty-two patients who already had implantation of a monofocal IOL in unilateral eye underwent implantation of a diffractive multifocal IOL in contralateral eye were enrolled.After 1,6,and 12 mo,uncorrected and distant corrected distant visual acuity(UCDVA and DCDVA),uncorrected and distant corrected intermediate-visual acuity(UCIVA and DCIVA),uncorrected and distant corrected near visual acuity(UCNVA and DCNVA),and contrast sensitivity were obtained.Halo/glare symptoms,spectacle dependence,and patient satisfaction were also evaluated.RESULTS:The mean age was 67.86±7.25 y and the average interval between two IOL implantations was 645.82±878.44 d.At 1 mo,binocular UCDVA was lower than 0.20 logMAR in 76%of patients(mean 0.12±0.13 logMAR),which increased to 90%by 6 and 12 mo.The binocular UCDVA was significantly better than the monocular results(P<0.05)at 1,6,and 12 mo.Additionally,UCNVA was lower than 0.40 logMAR in 82%of patients,increasing to 90%by 6 and 12 mo.Mean UCNVA in the multifocal IOL implanted eye was statistically significantly better than that in the monofocal IOL implanted eye(P<0.05)at 1,6,and 12 mo.About 5%of patients at 1 and 6 mo,reported"severe glare or halo".Patient satisfaction rates were 95%and 91%at 6 and 12 mo,respectively.CONCLUSION:Unilateral implantation of multifocal IOL in patients with a contralateral,monofocal IOL implantation results in high patient satisfaction rate,with low severe glare or halo rate during follow-up.It can represent a good option for patients who have previously had a monofocal IOL implantation regardless of two year interval duration between two IOL implantations.

Attenuation of corneal neovascularization by topical low-molecular-weight heparin-taurocholate 7 without bleeding complication

AIM：To investigate the antiangiogenic effects and safety of topically administered low-molecular-weight heparintaurocholate 7（LHT7） on corneal neovascularization（CoNV）.METHODS：Twenty-four Sprague-Dawley rats were randomly distributed into four groups of six rats each.The central corneas were cauterized using a silver/potassium nitrate solution.From 2d after cauterization,12.5 mg/mL（low LHT7 group） or 25 mg/mL（high LHT7group） LHT7 was topically administered three times daily;12.5 mg/mL bevacizumab was topically administered as positive control（bevacizumab） group,with normal saline（NS） administered as negative control（NS group）.The corneas were digitally photographed to calculate the CoNV percentage from the neovascularized corneal area at 1 and 2wk.RESULTS：The 4 study groups did not have different CoNV percentages at 1wk after injury（P〉0.05）.However,the low LHT,high LHT,and bevacizumab groups had significantly lower CoNV percentages than the NS group at 2wk（all P〈0.05）.No significant differences in CoNV percentage were found among the low LHT,high LHT,and bevacizumab groups（all P〉0.05）.All groups except the NS group had lower CoNV percentages at 2wk postinjury than the levels observed at 1wk（all P〈0.05）.CONCLUSION：Topically-administered LHT7 inhibited CoNV without complication after chemical cauterization in the rat.

A new multiple noncontinuous puncture(pointage)technique for corneal tattooing

AIMTo assess the safety and cosmetic efficacy of a new multiple noncontinuous transepithelial puncture technique for tattooing a decompensated cornea.METHODSIt was a non-comparative clinical case series study. The study examines 33 eyes in 33 patients with total corneal opacity due to corneal decompensation, which developed following intraocular surgery. Corneal tattooing was performed using the multiple noncontinuous transepithelial puncture technique (i.e. pointage). The safety of this new surgical strategy was assessed by occurrence of adverse events for the follow-up period. The cosmetic efficacy was determined by the patient's cosmetic satisfaction and independent observer's opinion about patient appearance.RESULTSSeven women and 26 men were included in the study. The mean age was 46.4&#x000b1;17.5y (range: 7-67). In total, 30 of 33 patients (91%) reported cosmetic satisfaction within the follow-up period. Only 3 patients (9%) required additional tattooing due to cosmetic unsatisfaction. Cosmetic outcomes were analyzed and classified as excellent or good in 13 (39%) and 17 (52%) patients, respectively. No serious adverse events developed, except delayed epithelial healing in 3 cases.CONCLUSIONThe cosmetic outcomes of the multiple noncontinuous transepithelial puncture technique for corneal tattooing were good. The safety of this method is higher than conventional procedures. This new procedure also provides improved cost-effectiveness and safety over current corneal tattooing techniques.

Topically administered bevacizumab had longer standing anti-angiogenic effect than subconjunctivally injected bevacizumab in rat corneal neovacularization

AIMTo compare the effect of topically administered and subconjunctivally injected bevacizumab on experimental corneal neovascularization in rats for two weeks after treatment.

In vivo biodistribution of topical low molecular weight heparin-taurocholate in a neovascularized mouse cornea

AIM： To investigate the ocular biodistribution and clearance of topically administered 7-taurocholic acid conjugated low-molecular weight heparin（LHT7） in a neovascularized mouse cornea using an in vivo optical imaging system. METHODS： A total of 10 eyes of 6 to 8-week-old BALB/c mice were analyzed. Corneal neovascularization（CoNV） was induced in the inferior cornea（IC） of each animal by penetrating the stroma with two interrupted sutures. The development of CoNV was verified after one week and the area of each neovascularized region was measured. A near-infrared fluorescent probe of 20 μmol/L Cy5.5 labeled LHT7（LHT7-Cy5.5） in 0.02 mL solution was topically instilled onto the cornea in the experimental group（n=5）. Free-Cy5.5 of 20 μmol/L in 0.02 mL was instilled in the control group（n=5）. In vivo optical images were obtained before instillation and 5 min, 2, 4, and 6 h after instillation. The intensities were separately measured at the superior cornea（SC） and the IC. RESULTS： The mean CoNV areas were 1.97±0.17 mm^2 and 1.92±0.96 mm^2 in the experimental and control groups, respectively（P=0.832）. The SC remained normal in all 10 subject animals. The IC intensity of the LHT7-Cy5.5 was greater than the SC intensity at 5 min（P=0.038）, 2 h（P=0.041）, and 4 h（P=0.041） after application. The IC intensity fell to less than half of its initial value（42.9%±8.6%） at 6 h in the experimental group. In the control mice, here were no significant differences in the free-Cy5.5 intensity between the IC and SC. CONCLUSION： Topically administered LHT7 shows a high biodistribution in CoNV areas for 4 h and should be reapplied accordingly to maintain its effects. In vivo optical imaging can be a useful tool for evaluating the ocular biodistribution of a drug in an animal model.