Melatonin delays photoreceptor degeneration in a mouse model of autosomal recessive retinitis pigmentosa.

Retinitis pigmentosa (RP) comprises a group of incurable inherited retinal degenerations. Targeting common processes, instead of mutation-specific treatment, has proven to be an innovative strategy to combat debilitating retinal degeneration. Growing evidence indicates that melatonin possesses a potent activity against neurodegenerative disorders by mitigating cell damage associated with apoptosis and inflammation. Given the pleiotropic role of melatonin in central nervous system, the aim of the present study was to investigate whether melatonin would afford protection against retinal degeneration in autosomal recessive RP (arRP). Rd10, a well-characterized murine model of human arRP, received daily intraperitoneal injection of melatonin (15 mg/kg) between postnatal day (P) 13 and P30. Retinas treated with melatonin or vehicle were harvested for analysis at P30 and P45, respectively. The findings showed that melatonin could dampen the photoreceptors death and delay consequent retinal degeneration. We also observed that melatonin weakened the expression of glial fibrillary acidic protein (GFAP) in Müller cells. Additionally, melatonin could alleviate retinal inflammatory response visualized by IBA1 staining, which was further corroborated by downregulation of inflammation-related genes, such as tumor necrosis factor alpha (Tnf-α), chemokine (C-C motif) ligand 2 (Ccl2), and chemokine (C-X-C motif) ligand 10 (Cxcl10). These data revealed that melatonin could ameliorate retinal degeneration through potentially attenuating apoptosis, reactive gliosis, and microglial activation in rd10 mice. Moreover, these results suggest melatonin as a promising agent improving photoreceptors survival in human RP.

Development of medical treatment for eye injuries in the mainland of China over the past decade.

In the article, the development of medical treatment for eye injuries in the mainland of China was reviewed. According to the data provided in Eye Injury Vitrectomy Study (EIVS), 27% of 72 eyes with no light perception (NLP) gained recovery in term of antomy and visual function. Vitrectomy initiated at more than 4 weeks after open eye injury is an independent risk factor for developing PVR. Prognosis of anatomy and visual function of the injured eye with PVR is markedly worse than that without PVR. Serious injuries of ciliary body, choroid and retina are three key parts of the eye with NLP. The concept that the treatment of the eye injury gradually focus on the whole globe is embodied. The data from 13575 in patients with traumatic eyes in 14 hospitals revealed that the rate of immediate enucleation was remarkable reduced with comparison of 20 years ago.

Protein tyrosine phosphatase 1B regulates the activity of retinal pigment epithelial cells.

PURPOSE: To determine whether protein tyrosine phosphatase 1B (PTP1B) is expressed in rat retinal pigment epithelium (RPE) cells, to evaluate whether inhibition of PTP1B contributes to initiation of RPE cells into an active state, and to investigate the signaling pathways involved in this process. METHODS: Rat retinas were detached by trans-scleral injection of 1.4% sodium hyaluronate into the subretinal space. Immunocytochemistry evaluated the expression of PTP1B in RPE cells located at normal and detached retinas. From the cultured RPE cells treated with TCS-401, cell proliferation was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetracolium bromide assay, and the protein expression levels of cyclin A and cyclin D1 were determined. The effect of TCS-401 on cell differentiation was confirmed by immunostaining for α-smooth muscle actin and by western blot. Cell migration activity and PTP1B signaling mechanism were determined. Migration Assay was used to evaluate cell migration activity. PTP1B signaling mechanism was determined by use of PD98059 and LY294002. RESULTS: PTP1B was expressed in the RPE layer of the normal retina. After retinal detachment, weak immunolabeling of PTP1B was seen in the RPE cells. TCS-401 promoted the proliferation and expression of cyclin A and cyclin D1 in RPE cells. TCS-401 induced RPE cells to differentiate toward better contractility and motility. A migration assay proved that inhibiting PTP1B improved the migratory activity of RPE cells. TCS-401 activated extracellular signal-regulated kinase (Erk) and protein kinase B (Akt) phosphorylation. Pretreatment with PD98059 and LY294002 abolished TCS-401-induced activation of Erk, Akt, cell proliferation, and cell migration. CONCLUSIONS: PTP1B may be involved in regulating the active state of RPE cells. The inhibition of PTP1B promoted the proliferation, myofibroblast differentiation, and migration of RPE cells, and MEK/Erk and PI3K/Akt signaling pathways played important roles in the proliferation and migration process.

Clinical features and prognosis of eyeball rupture: eye injury vitrectomy study.

BACKGROUND: The objective of the study was to delineate clinical characteristics, surgical interventions, anatomic and visual outcomes of ruptured eye balls after trauma, and establish the prognostic indicators, which can assist clinicians in making correct surgical decisions during globe exploration for ruptured eyes. DESIGN: The study design used was a multicentre prospective cohort study, including six university-affiliated tertiary hospitals. PARTICIPANTS: We selected 242 cases of ruptured globe from the Eye Injury Vitrectomy Study database, until 31 December 2012. METHODS: All selected cases underwent vitreoretinal surgery, enucleation or evisceration, and were followed up for at least 6 months. Age, visual acuity (VA) after injury, ocular trauma zone, time to surgery, corneal laceration, scleral wound, extrusion of iris or lens, ciliary body damage, intraocular haemorrhage, retinal detachment or defect, proliferative vitreoretinopathy (PVR) and choroidal damage were the predisposing factors evaluated by logistic regression models. MAIN OUTCOME MEASURES: We compared the pre-surgical indicators between cases of anatomically restored eyes with VA of 4/200 or better, or eyes with initial no light perception restored light perception or better, and cases of VA worse than 4/200, silicone oil-sustained eyes, phthisis or enucleation. RESULTS: Nearly 40% of cases with ruptured globe were anatomically restored through vitreoretinal surgery. The closed-funnel retinal detachment or extensive retinal loss (odds ratio [OR] = 3.38, P = 0.026), PVR-C (OR = 3.45, P = 0.008), and choroidal damage (OR = 4.20, P = 0.004) were correlated with poor outcomes. CONCLUSION: The closed-funnel retinal detachment or extensive retinal loss, PVR-C, and choroidal damage are the risk factors for unfavourable outcomes in globe ruptures.

Anti-neuroinflammatory efficacy of the aldose reductase inhibitor FMHM via phospholipase C/protein kinase C-dependent NF-κB and MAPK pathways.

Aldose reductase (AR) has a key role in several inflammatory diseases: diabetes, cancer and cardiovascular diseases. Therefore, AR inhibition seems to be a useful strategy for anti-inflammation therapy. In the central nervous system (CNS), microglial over-activation is considered to be a central event in neuroinflammation. However, the effects of AR inhibition in CNS inflammation and its underlying mechanism of action remain unknown. In the present study, we found that FMHM (a naturally derived AR inhibitor from the roots of Polygala tricornis Gagnep.) showed potent anti-neuroinflammatory effects in vivo and in vitro by inhibiting microglial activation and expression of inflammatory mediators. Mechanistic studies showed that FMHM suppressed the activity of AR-dependent phospholipase C/protein kinase C signaling, which further resulted in downstream inactivation of the IκB kinase/IκB/nuclear factor-kappa B (NF-κB) inflammatory pathway. Therefore, AR inhibition-dependent NF-κB inactivation negatively regulated the transcription and expression of various inflammatory genes. AR inhibition by FMHM exerted neuroprotective effects in lipopolysaccharide-induced neuron-microglia co-cultures. These findings suggested that AR is a potential target for neuroinflammation inhibition and that FMHM could be an effective agent for treating or preventing neuroinflammatory diseases.

[Some important aspects about treatment of open globe injury].

Open globe injury is a common cause for blindness. Injured eyes with no light perception (NLP) should not be enucleated before exploratory vitrectomy. Some NLP eyes may attain light perception or better vision through the vitrectomy. The decision of enucleation should be determined during exploratory vitrectomy. The timing of vitrectomy in the open globe injury still has controversy, but more surgeons agreed that vitrectomy should be performed within 2 weeks after open globe injury. The deadline of timing of vitrectomy is 4 weeks after injury. Retinectomy around the edge of the wound and retinal re-attachment surgery are the key points to prevent proliferative vitreoretinopathy resulted from the injury.

Electroacupuncture of Weizhong (BL-40) Acupoint Inspires Muscular Satellite Cell Regeneration and Promotes Muscle Repair Capacity after Back Muscle Injury in Sprague-Dawley Rat Model.

Background: Back muscle injury is the most common illness involved in aged people. Muscular satellite cells, playing a key role in the muscle repairing process, are gradually losing their regenerative ability with aging, which attenuates the injured muscle repairing process. Electroacupuncture at Weizhong acupoint has been widely used in the treatment of young and aged patients with back muscle damage. Its efficacy has been proven by a randomized double-blind placebo clinical trial. However, the rehabilitation mechanisms are largely unknown. This study will explore the possible mechanisms associated with electroacupuncture at the Weizhong acupoint (BL 40) promoting muscle repairing ability. Method: A total of 58 male and female Sprague-Dawley rats were divided into a younger group (4-month-old) and an aged group (16-month-old), younger and aged rats were further divided as a sham, injured, injured rats treated with electroacupuncture at Weizhong point or treated with Non-Weizhong point groups. The back muscle injury model was produced in rats as a previously described method with modification. Furthermore, Weizhong acupoints underwent electroacupuncture treatment with 15 V magnitude, 2 Hz/10 Hz frequency density, 1.0 mA current intensity, and 10 min each day for 10 consecutive days using HANS's electroacupuncture apparatus. After the last treatment, the paravertebral muscles and serum of all animals were undergone histological, immunohistochemistry, and flow cytometry analysis. Serum levels of Creatine Kinase (CK) and proinflammatory cytokine, interleukin 6 (IL-6), were measured separately by using ELISA kit. Results: Electroacupuncture of Weizhong (BL 40) acupoints significantly attenuated back muscle damage in both young and aged rats, increasing PAX7 (a marker of muscle satellite cells) and MYOD (major marker of myoblasts) cells, simultaneously, reducing serum proinflammatory cytokines, IL-6, and downregulation of p38 MAPK signaling in aged muscular satellite cells. Conclusion: Our studies suggest that electroacupuncture of Weizhong (BL 40) acupoints can restore aged back muscular satellite cells and their regeneration capacity. These suggested electroacupuncture may be a potential means of promoting rehabilitation for muscular injury in aged patients.

[The effect of descemet-stripping automated endothelial keratoplasty combined with phacoemulsification cataract surgery or lens exchange].

OBJECTIVE: To evaluate the effect and explore the complications of Descemet-stripping automated endothelial keratoplasty (DSAEK) combined with phacoemulsification cataract surgery or lens exchange in corneal endothelial dysfunction eyes with lens disorders. METHODS: Retrospective case series. Eighteen consecutive cases (20 eyes) were performed DSAEK combined with lens surgery from December 2007 to December 2008 in Department of Ophthalmology, Peking University Third Hospital. Five cases (7 eyes) were performed DSAEK combined with phacoemulsification and intraocular lens (IOL) insertion. Seven cases were combined with anterior chamber IOL extraction, anterior vitrectomy and posterior chamber IOL insertion. Six aphakia cases were performed with DSAEK combined with anterior vitrectomy and sclera fixation posterior chamber IOL insertion. Postoperatively, the visual acuity, corneal transparency, central corneal thickness (CCT), endothelial cell density (ECD) and complications were observed during the follow-up. RESULTS: The irritation was disappeared in all of patients. All of the corneas became transparent. The preoperative and postoperative mean CCT of the recipient beds was 859 µm and 553 µm respectively. T value was 5.303 (t = 5.303, P < 0.01). It was extremely significant difference. The mean ECD of the donors was 2987 cells/mm(2). The ECD was 1803 cells/mm(2) in three months postoperatively. The rate of endothelial cells loss was 41%. The visual acuity improved significantly except 9 eyes which had fundus disorders. Six eyes were better than 0.8. It was 55% in normal retinal function patients (6/11). The inflammatory reaction of the anterior chamber IOL eyes was most serious. Six eyes underwent graft dislocation. Five cases underwent high intraocular pressure. One case occurred graft rejection. These complications occurred in anterior chamber IOL eyes. CONCLUSIONS: DSAEK combined with phacoemulsification cataract surgery or lens exchange is a safe and effective surgical treatment for corneal endothelial dysfunction with lens disorders. More complications occur in anterior chamber IOL eyes. DSAEK should be cautiously chosen in abnormal iris and chamber angle structural eyes.

Traumatic choroidal injuries - classification, incidence, diagnosis and prognosis twenty-year results of Eye Injury Vitrectomy Study.

PURPOSE: To characterize the classification, incidence, diagnosis and prognosis of traumatic choroidal injuries. METHODS: Subjects were selected from the database of the Eye Injury Vitrectomy Study (EIVS) and were examined for occurrences of different categories of choroidal injuries. Standard photographs were collected. Anatomical and visual outcomes were assessed in patients with greater than 1 year of follow-up. Eyes that had no light perception (NLP) and/or phthisis bulbi were defined as having had unfavourable outcomes. The percentage of eyes with an unfavourable outcome was analysed for different types of choroidal injuries. RESULTS: Nine categories of choroidal injuries with distinctive features were identified in the EIVS database. The incidence and the percentage of eyes with an unfavourable outcome in each injury category were as follows: suprachoroidal effusion, 21.2% (7.2%); suprachoroidal haemorrhage, 12.8% (11.2%); massive suprachoroidal haemorrhage, 4.0% (64.9%); choroidal avulsion, 4.2% (92.2%); traumatic chorioretinal rupture, 1.8% (13.3%); choroidal rupture, 4.8% (6.8%); choroidal loss, 1.6% (79.3%); choroidal hole, 1.1% (5.3%); and choroidal damage at the wound site, 39.2% (17.7%). CONCLUSIONS: Ocular trauma can cause a variety of choroidal injuries that have distinctive features, some of which are associated with a high frequency of unfavourable prognoses.

Jianpi Qushi Heluo Formula alleviates renal damages in Passive Hemann nephritis in rats by upregulating Parkin-mediated mitochondrial autophagy.

Jianpi Qushi Heluo Formula (JQHF) is an empirical traditional Chinese medicine prescription for treating Membranous Nephropathy (MN) clinically in China. The therapeutic effect of JQHF has been reported in our previous studies. However, the exact mechanism is still unknown. In this study, by establishing an experimental rat model of MN induced by Sheep anti-rat Fx1A serum, we evaluated the effects of JQHF and Tetrandrine (TET), and Benazepril was used as a positive control. As an autophagy agonist, TET is one of the most active components in JQHF. After 4 weeks, significant kidney damage was observed in the rats in the Model group; comparatively, JQHF markedly decreased 24 h urinary protein, Total Cholesterol (TC), and increased serum total Albumin (ALB). Histology showed that JQHF caused significant improvements in glomerular hyperplasia, renal tubular damage, IgG immune complex deposition, and the ultrastructure of mitochondria in MN rats. Flow cytometry analysis showed that treatment with JQHF reduced the level of reactive oxygen species and apoptosis rate, and upregulated mitochondrial membrane potential. Western blot analysis demonstrated that JQHF could protect against mitochondrial dysfunction and apoptosis by upregulating the expression of PINK1, Mitochondrial Parkin, and LC3-II/I, downregulating the expression of Cytoplasmic Parkin, P62, Cytochrome c, and Caspase-3 in the kidneys of MN rats. From images of co-immunofluorescence, it is observed significantly increase in the co-localization of PINK1 and Parkin, as well as LC3 and mitochondria. Similarly, TET treatment significantly upregulated the mitochondrial autophagy and reduced apoptosis in rats after 4 weeks compared with the model group. Comparatively, the ability of JQHF to alleviate renal damage was significantly higher than those of Benazepril and TET. It was demonstrated that JQHF could delay pathology damage to the kidney and hold back from the progression of MN by inhibiting apoptosis and upregulating the mitochondrial autophagy by PINK1/Parkin pathways.

Prognostic factors and long-term outcomes of eye-globe perforation: Eye injury vitrectomy study.

PURPOSE: To delineate anatomic and visual outcomes of injured eye globes with perforating, and to develop the prognostic indicators for perforating eyes. METHODS: The case series study, from a multicenter prospective cohort database. To the date of December 31st, 2018, of 63 perforating globes were selected. All cases underwent vitreoretinal surgeries or enucleations, and were followed up for at least 6 months. Demographic characteristics, basic examination for traumatized eyes, and intraocular tissue damages were recorded by surgery-in-chief. At the follow-up visit, best corrected VA, intraocular pressure, the intraocular tamponade material, retinal anatomic outcome of eye-globes, and phthisis or enucleation were evaluated. RESULTS: Fifty injured eyes (79%) were caused by sharp objects and 13 eyes (21%) were injured by a missiles. Twenty-two injured eyes can be anatomically restored with final vision of more than 4/200 through vitreoretinal surgery. The PVR-C (OR = 5.67, P = 0.01), area of retinectomy more than 2 times of optic disk (OR = 5.16, P = 0.04), and macular damage (OR = 6.38, P = 0.01) were correlated with unfavorable outcomes. CONCLUSION: The injured eyes with perforation can be saved through vitreoretinal surgery, the PVR-C, retinectomy more than 2 times of optic disk, and macular damage were independent risk factors for poor long-term prognosis.

Mechanism and prognostic indicators for explosion-related eye trauma: eye injury vitrectomy study.

PURPOSE: To explore the clinical features, surgical interventions and prognosis of injured eyes following explosion and to develop the risk factors for poor prognosis. METHODS: A nested case-control study. To the date of 31 December 2018, 99 explosion-related eye globes were selected from the Eye Injury Vitrectomy Study database, which is a multicenter prospective cohort study and began in 1990s. All cases selected underwent vitreoretinal surgery or enucleation and were followed up for at least 6 months. Clinically meaningful preoperative variables and outcomes were used to develop logistic regression models. RESULTS: The unfavourable outcomes were defined as silicone oil-filled eyes, phthisis bulbi, enucleation and anatomically restored eyes whose final BCVA is worse than initial vision after 6 months of follow-up. The proportion of unfavourable outcomes was 92.0%, 60.9% and 66.7% in large festive fireworks, detonator and beer bottle groups respective. The anatomic and visual outcome of injured eyes with combined injury of blast wave and projectile were worse than that of ruptured eyes (Fisher's exact = 0.041). The extrusion of iris/lens (OR = 3.20, p = 0.015), PVR-C (OR = 6.08, p = 0.036) and choroid damage (OR = 5.84, p = 0.025) is independent risk factors of unfavourable prognosis for explosion-related eye trauma. CONCLUSION: The extrusion of iris/lens, PVR-C and choroid damage is the independent risk factors for unfavourable outcomes in explosion-related eye trauma. There is a unique injury mechanism in explosion-related eye trauma. SUMMARY STATEMENT: Through the nested case-control study, the extrusion of iris/lens, PVR-C, and choroid damage are the independent risk factors for unfavorable outcomes in explosion-related eye trauma. The mechanism of open globe mixture and close globe mixture in explosion-related eye trauma need more cases and participating units to explore together in the future.

Usefulness of frequency-doubling technology for perimetrically normal eyes of open-angle glaucoma patients with unilateral field loss.

PURPOSE: To determine whether frequency-doubling technology (FDT) perimetry detects visual field loss in perimetrically normal eyes of patients with open-angle glaucoma (OAG) and whether these visual field defects subsequently are detected by standard automated perimetry (SAP), and to explore the relating factors of the progression from abnormalities based on FDT to visual field loss based on SAP. DESIGN: Prospective cohort study. PARTICIPANTS: Sixty-eight OAG patients with unilateral field loss detected by SAP (Octopus, G2 program; Interzeig, Schlieren, Switzerland). METHODS: Perimetrically normal eyes of participants were examined with the FDT N-30 threshold program (Humphrey Instruments, Welch-Allyn, Skaneateles, NY). The visual field examination was followed by a series of SAP examinations administered over 3 years. MAIN OUTCOME MEASURES: The relationship between FDT and subsequent SAP results in perimetrically normal eyes was analyzed. Glaucomatous optic neuropathy (GON), visual field indices, intraocular pressure (IOP), and central corneal thickness (CCT) were compared between converters (eyes with subsequent SAP abnormality) and nonconverters within perimetrically normal eyes with abnormal FDT results. Finally, the SAP test points were matched to the abnormal FDT sectors. The relative risk (RR) of subsequent SAP abnormality corresponding to FDT abnormal sectors was calculated. RESULTS: Sixty perimetrically normal eyes of 60 participants had complete data and a qualifying follow-up. Baseline FDT results were abnormal in 65%. Of the eyes with abnormal FDT results, 51% developed abnormal SAP results after 4 to 27 months, whereas none of the eyes with normal FDT results developed abnormal SAP results (P<0.05). In perimetrically normal eyes with abnormal FDT results, converters had a greater cup-to-disc ratio, more eyes with GON, larger and deeper cups, and worse FDT mean deviation than nonconverters (P<0.05). The IOP and CCT did not differ between the 2 groups. The RR of subsequent SAP abnormality corresponding to abnormal FDT sectors was 5.38 (95% confidence interval, 3.61-8.04; P<0.05). CONCLUSIONS: In perimetrically normal eyes of OAG patients, FDT detected visual field loss in almost 2 of every 3 of these eyes and also predicted to some extent future visual field loss on SAP. Severity of glaucomatous neuropathy at baseline was related to conversion of abnormalities on FDT to visual field loss on SAP.

The effects of sodium orthovanadate-induced phosphatase inhibition on rat retinal pigment epithelium cell activity.

PURPOSE: The purpose of this study was to assess the contribution of sodium orthovanadate (SOV)-induced phosphatase inhibition to the activation of rat retinal pigment epithelium (RPE) cells. METHODS: Confluent cultures of rat RPE cells were treated with the general phosphatase inhibitor SOV. The effects of SOV on the cell cycle were determined by flow cytometry and protein detection of cyclin A and cyclin D1, two different cell cycle regulatory factors. The effects of SOV on cell differentiation were confirmed by immunostaining for α-smooth muscle actin (α-SMA). A migration assay was used to evaluate the effects of SOV on cell migration. RESULTS: SOV could accelerate the cell cycle of RPE cells. Western blotting showed that SOV significantly increased the expression of cyclin A and cyclin D1 in a dose-dependent fashion. The results of α-SMA staining and western blotting demonstrated that SOV induced RPE cells to differentiate toward better contractility and motility. The migration assay indicated that SOV improved the migration activity of RPE cells. CONCLUSIONS: Sodium orthovanadate can improve proliferation, differentiation, and migration of rat RPE cells and can also induce the reentry of contact-inhibited rat RPE cells into the cell cycle.

[Eye injuries in China: a five-year update].

Remarkable advance for the treatment of opening eye injuries have been achieved in the past 5 years. Very valuable results have been obtained from the database of cumulative studies on eye injuries managed with vitrectomy. Timing of vitrectomy for opening-injured eyes was a significant factor to influence their outcome. Estimation of a quarter of injured eyes with no light perception could gain anatomic recovery with various improvement of visual acuity. Previous conventional treatment pattern for opening anterior segment injury lacked proper debridement on inside of wound which resulted unfavorable outcome. Vitrectomy at early stage (1-3 weeks after initial repair of wound) in selected cases could be a recommended treatment to improve outcomes in opening anterior segment injury.

[Clinical study of Descemet membrane stripping with automated endothelium keratoplasty].

OBJECTIVE: To investigate the clinical efficacy, prevention and management complications and choice of indication with Descemet membrane stripping with automated endothelium keratoplasty (DSAEK). METHODS: Clinical case series. Nine patients (9 eyes) with bullous keratopathy underwent DSAEK procedure from Peking University Eye Center, Peking University Third Hospital during September to December in 2007. Visual acuity, cornea transparency, graft position, corneal thickness, curvature, astigmatism and endothelial cells density (ECD) were observed over 3-7 month follow-up period. RESULTS: One patient with iris cornea endothelium syndrome was fail to insert graft into anterior chamber and changed procedure to penetrating keratoplasty. Eight patient successfully performed procedure. One graft dislocation in was managed in first day after surgery. All 8 grafts remained transparent and improved visual acuity. After surgery, mean corneal thickness was (775 +/- 30)microm. Mean corneal curvature was (44.19 +/- 2.28) D. Mean corneal astigmatism was (2.20 +/- 0.83) D. Mean endothelial cells density was (1439 +/- 296) cells/mm(2). CONCLUSIONS: DSAEK is a less damage, faster recovery vision, safer procedure. It is expected to be the important procedure to treat bullous keratopathy.

[Evaluation of toxicity of manganese ions to rabbit retina].

OBJECTIVE: To research the Mn(2+) toxicity in vivo rabbit retina. Mn(2+) is used as a tracer in MRI. METHODS: It was an experimental study. Sixty pigmented rabbits (120 eyes) were divided into 5 groups randomly. Manganese chloride solution 25 µl of 10, 15, 20, 30, 40 mmol/L were injected intravitreally in one eye of each rabbit respectively as 5 experimental groups (n = 12). The saline (0.9%) 25 µl was injected intravitreally in other eye of each rabbit as control group (60 eyes). After intravitreal injections, all eyes were examined by color fundus camera, fluorescein angiography, flash electroretinography, light microscopy, and transmission electron microscopy on the 0(th), 7(th), and 28(th) day. RESULTS: On the 7(th) day after intravitreal injection, the average of the F-ERG b-wave amplitude was reduced significantly from 337 µV to 189 µV in the group of 15 mmol/L (F = 20.43, P < 0.05), but the amplitude was returned to normal on the 28(th) day. On the 7(th) day after intravitreal injections, the F-ERG b-wave amplitude was reduced significantly in the group of ≥ 20 mmol/L, and the amplitude was not returned to normal on the 28(th) day. There were abnormal changes in the structure of the retina in ≥ 20 mmol/L group at difference time after intravitreal injections. CONCLUSION: MnCl(2) as a tracer in vivo optic nerve, the concentration of ≤ 15 mmol/L caused only reversible changes in retinal function; The concentration of ≥ 20 mmol/L appears, damages in retinal function and morphology appeared.

Effect of intravitreal ranibizumab pretreatment on vitrectomy in young patients with proliferative diabetic retinopathy.

BACKGROUND: Younger patients who underwent vitrectomy for proliferative diabetic retinopathy (PDR) display more aggressive nature distinguished from the older patients. Preoperative anti-VEGF therapy has been widely used as an adjunct for PDR surgery. However, the effect of anti-VEGF administration in young diabetics has rarely been evaluated in previous studies. The purpose of this study was to evaluate the effects of ranibizumab pretreatment on vitrectomy surgery in young patients with PDR. METHODS: This was a prospective nonrandomized comparative study. Young patients (<40 years old) undergoing diabetic vitrectomy with or without ranibizumab pretreatment (25 eyes in each group) were analyzed in this study. The use of the drug was determined by the patients' own preference. The two surgical groups were matched according to a complexity score. Intravitreal injection of ranibizumab (IVR) was performed 3-5 days prior to the vitrectomy surgery in the IVR group. Intraoperative records including total surgical time, intraoperative bleeding, the use of endodiathermy, the frequency of relaxing retinotomies, the incidence of iatrogenic retinal breaks, and the use of perfluorocarbon liquid (PFCL) and silicone oil tamponade, and postoperative indices regarding recurrent vitreous hemorrhage (VH), neovascular glaucoma (NVG), recurrent retinal detachment, and visual outcome were evaluated between the two groups. All patients were followed up for one year after surgery. RESULTS: In young PDR patients, the severity of intraoperative bleeding was significantly lower in the IVR group than in the control group (P=0.04). The total surgical time was shorter in the IVR group than in the control group. However, the rate of relaxing retinotomy, the incidence of iatrogenic retinal breaks and the use of PFCL and silicone oil tamponade were not affected by IVR pretreatment but affected by the complexity score of the case. Early postvitrectomy hemorrhage occurred less frequently in the IVR group than in the control group (P<0.001), Early visual recovery was better in the IVR group than in the control group (P=0.03). However, there were no significant differences in the development of late recurrent VH, NVG, recurrent retinal detachment, and final visual outcome. CONCLUSIONS: IVR pretreatment is a safe and effective adjunct to vitrectomy in reducing intraoperative and early postvitrectomy bleeding and should be suggested in young PDR patients. However, IVR does not reduce the incidence of intraoperative and late postoperative complications in these patients. The risk of iatrogenic retinal breaks and silicone oil use are closely correlated with the complexity score of the surgical cases.

Simultaneous expression of two pathogenic genes in four Chinese patients affected with inherited retinal dystrophy.

AIM: To describe the complex, overlapping phenotype of four Chinese patients with inherited retinal dystrophies (IRDs) who harbored two pathogenic genes simultaneously. METHODS: This retrospective study included 4 patients affected with IRDs. Medical and ophthalmic histories were obtained, and clinical examinations were performed. A specific Hereditary Eye Disease Enrichment Panel (HEDEP) based on exome capture technology was used for genetic screening. RESULTS: Four patients were identified to harbor disease-causing variants in two different genes. Patient retinitis pigmentosa (RP) 01-II:1 exhibited both classical ABCA4-induced Stargardt disease (STGD) 1 and USH2A-associated RP, patient RP02-III:2 exhibited both classical ABCA4-induced STGD1 and CDH23-associated RP, patient RP03-II:1 exhibited both USH2A-induced autosomal recessive retinitis pigmentosa (arRP) syndrome and SNRNP200-induced autosomal dominant retinitis pigmentosa (adRP), and patient RP04-II:2 exhibited USH2A-induced arRP syndrome and EYS-induced arRP at the same time. CONCLUSION: Our study demonstrates that genotype-phenotype correlations and comprehensive genetic screening is crucial for diagnosing IRDs and helping family planning for patients suffering from the disease.

Echinacoside elicits endothelium-dependent relaxation in rat aortic rings via an NO-cGMP pathway.

The aim of this study was to identify and elucidate the vasorelaxant activity of echinacoside, a phenylethanoid glycoside isolated from the medicinal herb Cistanche tubulosa, and its possible underlying mechanism on isolated rat thoracic aortic rings pre-contracted with phenylephrine (PE, 1 microM) and KCl (60 mM). Echinacoside (30-300 microM) exhibited an acute relaxation in endothelium-intact rings in a concentration-dependent manner, while this relaxation was significantly inhibited in endothelium-denuded condition and in the presence of the endothelial nitric oxide synthase (eNOS) inhibitor, N(W)-nitro-L-arginine methyl ester (L-NNA, 100 microM), an unselective soluble guanylate cyclase blocker, methylene blue (10 microM), the selective sGC inhibitor 1 H-[1, 2, 4]oxadiazolo[4,3- A]quinoxalin-1-one (ODQ, 1 microM); in addition, atropine (1 microM), a selective muscarinic receptor antagonist, partially affected the relaxation. However, the cyclooxygenase inhibitor indomethacin (5 microM) had no influence on the action. Echinacoside enhanced the cyclic guanosine monophosphate (cGMP) production in aortic rings contracted with PE. These results indicate for the first time that echinacoside mediates the endothelium-dependent vasodilator action in rat thoracic aortic rings through nitric oxide (NO)-cGMP pathway.