Myosin 1f-mediated activation of microglia contributes to the photoreceptor degeneration in a mouse model of retinal detachment

Photoreceptor death and neurodegeneration is the leading cause of irreversible vision loss. The inflammatory response of microglia plays an important role in the process of neurodegeneration. In this study, we chose retinal detachment as the model of photoreceptor degeneration. We found Myosin 1f was upregulated after retinal detachment, and it was specifically expressed in microglia. Deficiency of myosin 1f protected against photoreceptor apoptosis by inhibiting microglia activation. The elimination of microglia can abolish the protective effect of myosin 1f deficiency. After stimulation by LPS, microglia with myosin 1f deficiency showed downregulation of the MAPK and AKT pathways. Our results demonstrated that myosin 1f plays a crucial role in microglia-induced neuroinflammation after retinal injury and photoreceptor degeneration by regulating two classic inflammatory pathways and thereby decreasing the expression of inflammatory cytokines. Knockout of myosin 1f reduces the intensity of the immune response and prevents cell death of photoreceptor, suggesting that myosin 1f can be inhibited to prevent a decline in visual acuity after retinal detachment.Subject terms: Neuroimmunology, Retina     

Acute injuries in soccer,ice hockey,volleyball, basketball,judo, and karate: analysis of national registry data.

OBJECTIVE--To determine the acute injury profile in each of six sports and compare the injury rates between the sports. DESIGN--Analysis of national sports injury insurance registry data. SETTING--Finland during 1987-91. SUBJECTS--621,691 person years of exposure among participants in soccer, ice hockey, volleyball, basketball, judo, or karate. MAIN OUTCOME MEASURES--Acute sports injuries requiring medical treatment and reported to the insurance company on structured forms by the patients and their doctors. RESULTS--54,186 sports injuries were recorded. Injury rates were low in athletes aged under 15, while 20-24 year olds had the highest rates. Differences in injury rates between the sports were minor in this adult age group. Overall injury rates were higher in sports entailing more frequent and powerful body contact. Each sport had a specific injury profile. Fractures and dental injuries were most common in ice hockey and karate and least frequent in volleyball. Knee injuries were the most common cause of permanent disability. CONCLUSIONS--Based on the defined injury profiles in the different sports it is recommended that sports specific preventive measures should be employed to decrease the number of violent contacts between athletes, including improved game rules supported by careful refereeing. To prevent dental injuries the wearing of mouth guards should be encouraged, especially in ice hockey, karate, and basketball.     

Tauroursodeoxycholic acid (TUDCA) protects photoreceptors from cell death after experimental retinal detachment

Background

Detachment of photoreceptors from the underlying retinal pigment epithelium is seen in various retinal disorders such as retinal detachment and age-related macular degeneration and leads to loss of photoreceptors and vision. Pharmacologic inhibition of photoreceptor cell death may prevent this outcome. This study tests whether systemic administration of tauroursodeoxycholic acid (TUDCA) can protect photoreceptors from cell death after experimental retinal detachment in rodents.

Methodology/Principal Findings

Retinal detachment was created in rats by subretinal injection of hyaluronic acid. The animals were treated daily with vehicle or TUDCA (500 mg/kg). TUNEL staining was used to evaluate cell death. Photoreceptor loss was evaluated by measuring the relative thickness of the outer nuclear layer (ONL). Macrophage recruitment, oxidative stress, cytokine levels, and caspase levels were also quantified. Three days after detachment, TUDCA decreased the number of TUNEL-positive cells compared to vehicle (651±68/mm² vs. 1314±68/mm², P = 0.001) and prevented the reduction of ONL thickness ratio (0.84±0.03 vs. 0.65±0.03, P = 0.002). Similar results were obtained after 5 days of retinal detachment. Macrophage recruitment and expression levels of TNF-a and MCP-1 after retinal detachment were not affected by TUDCA treatment, whereas increases in activity of caspases 3 and 9 as well as carbonyl-protein adducts were almost completely inhibited by TUDCA treatment.

Conclusions/Significance

Systemic administration of TUDCA preserved photoreceptors after retinal detachment, and was associated with decreased oxidative stress and caspase activity. TUDCA may be used as a novel therapeutic agent for preventing vision loss in diseases that are characterized by photoreceptor detachment.     

Fibulin 2, a Tyrosine O-Sulfated Protein,Is Up-regulated Following Retinal Detachment

Retinal detachment is the physical separation of the retina from the retinal pigment epithelium. It occurs during aging, trauma, or during a variety of retinal disorders such as age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, or as a complication following cataract surgery. This report investigates the role of fibulin 2, an extracellular component, in retinal detachment. A major mechanism for detachment resolution is enhancement of cellular adhesion between the retina and the retinal pigment epithelium and prevention of its cellular migration. This report shows that fibulin 2 is mainly present in the retinal pigment epithelium, Bruch membrane, choriocapillary, and to a lesser degree in the retina. In vitro studies revealed the presence of two isoforms for fibulin 2. The small isoform is located inside the cell, and the large isoform is present inside and outside the cells. Furthermore, fibulin 2 is post-translationally modified by tyrosine sulfation, and the sulfated isoform is present outside the cell, whereas the unsulfated pool is internally located. Interestingly, sulfated fibulin 2 significantly reduced the rate of cellular growth and migration. Finally, levels of fibulin 2 dramatically increased in the retinal pigment epithelium following retinal detachment, suggesting a direct role for fibulin 2 in the re-attachment of the retina to the retinal pigment epithelium. Understanding the role of fibulin 2 in enhancing retinal attachment is likely to help improve the current therapies or allow the development of new strategies for the treatment of this sight-threatening condition.     

Bone marrow mesenchymal stem cells enhance autophagy and help protect cells under hypoxic and retinal detachment conditions

Our study aimed to evaluate the protective role and mechanisms of bone marrow mesenchymal stem cells (BMSCs) in hypoxic photoreceptors and experimental retinal detachment. The cellular morphology, viability, apoptosis and autophagy of hypoxic 661w cells and cells cocultured with BMSCs were analysed. In retinal detachment model, BMSCs were intraocularly transplanted, and then, the retinal morphology, outer nuclear layer (ONL) thickness and rhodopsin expression were studied as well as apoptosis and autophagy of the retinal cells. The hypoxia-induced apoptosis of 661w cells obviously increased together with autophagy levels increasing and peaking at 8 hours after hypoxia. Upon coculturing with BMSCs, hypoxic 661w cells had a better morphology and fewer apoptosis. After autophagy was inhibited, the apoptotic 661w cells under the hypoxia increased, and the cell viability was reduced, even in the presence of transplanted BMSCs. In retina-detached eyes transplanted with BMSCs, the retinal ONL thickness was closer to that of the normal retina. After transplantation, apoptosis decreased significantly and retinal autophagy was activated in the BMSC-treated retinas. Increased autophagy in the early stage could facilitate the survival of 661w cells under hypoxic stress. Coculturing with BMSCs protects 661w cells from hypoxic damage, possibly due to autophagy activation. In retinal detachment models, BMSC transplantation can significantly reduce photoreceptor cell death and preserve retinal structure. The capacity of BMSCs to reduce retinal cell apoptosis and to initiate autophagy shortly after transplantation may facilitate the survival of retinal cells in the low-oxygen and nutrition-restricted milieu after retinal detachment.     

兔眼孔源性视网膜脱离手术复位后视功能以及超微结构的变化

目的对比研究兔眼视网膜脱离后选择不同时期手术复位视功能的变化情况,为临床手术时机的选择及预测术后视功能的恢复情况提供理论与实验依据。方法利用家兔制备孔源性视网膜脱离模型,成模后1 d、7 d1、4 d时经手术达解剖复位,采用多焦视网膜电流图检测复位后视网膜的功能,数据处理应用SPSS软件。制备组织病理学切片。结果多焦视网膜电流图显示1 d、7 d、14 d的RRD手术复位后P1波平均象限反应密度(QAP1,nV/deg2),P1波幅值(AP1,μV),N1波幅值(AN1,μV),P1波潜伏期(TP1,ms),N1波潜伏期(TN1,ms)各项数值差异有显著性(P<0.05)。光镜电镜显示视网膜脱离复位后组织病理学改变。结论视网膜脱离手术复位后视网膜细胞功能的恢复与脱离时间有明显的负相关性;多焦视网膜电流图对于局部视网膜功能的评价有重要意义;组织病理学研究提供了解释视功能变化的重要依据。     

A Case Report of Intravitreal Dexamethasone Implant with Exudative Retinal Detachment for Ocular Toxocariasis Treatment

Toxocariasis is one of the most common geohelminth infections in several parts of the world. We describe a rare case of ocular toxocariasis with secondary exudative retinal detachment treated with albendazole and an intravitreal dexamethasone implant. A 13-year-old boy with counting finger vision was diagnosed with retinal vasculitis and exudative retinal detachment in his right eye. Fundoscopic examination revealed retinal hemorrhage, retinal vasculitis, and exudative retinal detachment. Serological test using serum and intraocular aqueous humor were positive for anti-Toxocara specific IgG antibodies. He received repeated doses of intravitreal dexamethasone implants combined with oral albendazole. A sequential follow-up optical coherence tomography revealed that the retina was successfully reattached. His visual acuity subsequently improved to 20/400.     

Axial eye length after retinal detachment surgery

Changes in the eye axial diameter were studied to assess the eye globe impact of conventional operation for retinal detachment. The study included 69 eyes in 69 patients operated on for rhegmatogenous retinal detachment. There were 46.4% of men and 53.6% of women, mean age 52.7 (+/- 15.21) years. Results of preoperative and postoperative ultrasonographic measurement of axial diameter are presented. The mean preoperative and postoperative eye axial diameter was 23.69 (+/- 1.84) mm and 24.43 (+/- 1.91) mm, respectively. Postoperative results showed the axial eye length to increase by a mean of 0.74 (+/- 0.44) mm, yielding a statistically significant difference from the preoperative measurement (p < 0.001). The mean myopia induced by this eyeball elongation was 1.77 D. The encircling band with and without segmental buckling used in surgical repair of retinal detachment creates circular and segmental indentation of the eyeball, thus increasing its axial length. The myopia induced by elongation of the eyeball results in considerable myopia, which requires appropriate correction in the early postoperative period to achieve favorable vision rehabilitation.     

Risk of injury associated with bodychecking experience among youth hockey players

Background:

In a previous prospective study, the risk of concussion and all injury was more than threefold higher among Pee Wee ice hockey players (ages 11–12 years) in a league that allows bodychecking than among those in a league that does not. We examined whether two years of bodychecking experience in Pee Wee influenced the risk of concussion and other injury among players in a Bantam league (ages 13–14) compared with Bantam players introduced to bodychecking for the first time at age 13.

Methods:

We conducted a prospective cohort study involving hockey players aged 13–14 years in the top 30% of divisions of play in their leagues. Sixty-eight teams from the province of Alberta (n = 995), whose players had two years of bodychecking experience in Pee Wee, and 62 teams from the province of Quebec (n = 976), whose players had no bodychecking experience in Pee Wee, participated. We estimated incidence rate ratios (IRRs) for injury and for concussion.

Results:

There were 272 injuries (51 concussions) among the Bantam hockey players who had bodychecking experience in Pee Wee and 244 injuries (49 concussions) among those without such experience. The adjusted IRRs for game-related injuries and concussion overall between players with bodychecking experience in Pee Wee and those without it were as follows: injury overall 0.85 (95% confidence interval [CI] 0.63 to 1.16); concussion overall 0.84 (95% CI 0.48 to 1.48); and injury resulting in more than seven days of time loss (i.e., time between injury and return to play) 0.67 (95% CI 0.46 to 0.99). The unadjusted IRR for concussion resulting in more than 10 days of time loss was 0.60 (95% CI 0.26 to 1.41).

Interpretation:

The risk of injury resulting in more than seven days of time loss from play was reduced by 33% among Bantam hockey players in a league where bodychecking was allowed two years earlier in Pee Wee compared with Bantam players introduced to bodychecking for the first time at age 13. In light of the increased risk of concussion and other injury among Pee Wee players in a league where bodychecking is permitted, policy regarding the age at which hockey players are introduced to bodychecking requires further consideration.Rates of participation in youth-level ice hockey are high in North America.^1,2 There is growing concern regarding the impact of concussion in this population.^3–5 Body-checking is the reported mechanism for 45%–86% of injuries in youth ice hockey.^5–11 Internationally, the age group at which bodychecking is introduced varies. In Canada, bodychecking is introduced in Pee Wee leagues (ages 11–12 years), except in the province of Quebec, where it is introduced in Bantam (ages 13–14).¹²The age at which bodychecking should be introduced is controversial. We recently reported that the risk of injury and concussion in a Pee Wee league that allows bodychecking was more than threefold higher than in a Pee Wee league that does not allow bodychecking.⁹ Findings from systematic reviews support these findings.^13,14Injury rates may increase when players begin to learn bodychecking, because it is a new skill. If so, injury rates would be expected to be higher among players without bodychecking experience in Pee Wee (i.e., those in Quebec) than among players introduced to body-checking two years earlier in Pee Wee (e.g., in Alberta). We examined whether the risk of concussion and other injury among hockey players in Bantam leagues differed between players with and those without bodychecking experience in Pee Wee.     

The biomechanics of concussion for ice hockey head impact events

The purpose of this research was to conduct reconstructions of concussive and non-concussive impacts in ice hockey to determine the biomechanics and thresholds of concussive injury in ice hockey. Videos of concussive and non-concussive impacts in an elite professional ice hockey league in North America were reconstructed using physical and finite element model methods. Eighty concussive and 45 non-concussive events were studied. Logistic regressions indicate significant thresholds for concussion for linear/rotational acceleration and CSDM_10%. Impacts in ice hockey were mostly long duration events, longer than 15?ms. These results have significant implications for helmet standards and development to prevent concussion.     

Ocular angiostrongyliasis without meningitis symptoms in Okinawa,Japan

A 62-year-old female farmer presented with retinal detachment in her left eye, and an Angiostrongylus cantonensis worm was recovered by vitreous surgery. The case did not show typical clinical symptoms indicating meningitis, although the patient complained of a mild headache, a low-grade fever, and slight ataxia. The symptoms were treated as influenza before the onset of the retinal detachment. The present case is the first confirmed of ocular angiostrongyliasis in Japan.     

Neuron-specific TGF-beta signaling deficiency results in retinal detachment and cataracts in mice

We generated a mouse model (cKO) with a conditional deletion of TGF-beta signaling in the retinal neurons by crossing TGF-beta receptor I (TGF-beta RI) floxed mice with nestin-Cre mice. Almost all of the newborn cKO mice had retinal detachment at the retinal pigment epithelium (RPE)/photoreceptor layer junction of the neurosensory retina (NSR). The immunostaining for chondroitin-6-sulfate showed a very weak reaction in cKO mice in contrast to intense staining in the photoreceptor layer in wild-type mice. Macroscopic cataracts, in one or both eyes, were observed in 50% of the mice by 6 months of age, starting as early as the first month after birth. The cKO mouse model demonstrates that the TGF-beta signaling deficiency in retinal cells leads to decreased levels of chondroitin sulfate proteoglycan in the retinal interphotoreceptor matrix. This in turn causes retinal detachment due to the loss of adhesion of the NSR to RPE.     

Experimental retinal detachment causes widespread and multilayered degeneration in rabbit retina

Retinal detachment remains one of the most frequent causes of visual impairment in humans, even after ophthalmoscopically successful retinal reattachment. This study was aimed at monitoring (ultra-) structural alterations of retinae of rabbits after experimental detachment. A surgical procedure was used to produce local retinal detachments in rabbit eyes similar to the typical lesions in human patients. At various periods after detachment, the detached retinal area as well as neighbouring attached regions were studied by light and electron microscopy. In addition to the well-known degeneration of photoreceptor cells in the detached retina, the following progressive alterations were observed, (i) in both the detached and the attached regions, an incomplete but severe loss of ganglion cell axons occurs; (ii) there is considerable ganglion cell death, particularly in the detached area; (iii) even in the attached retina distant from the detachment, small adherent groups of photoreceptor cells degenerate; (iv) these photoreceptor cells degenerate in an atypical sequence, with severely destructed somata and inner segments but well-maintained outer segments; and (v) the severe loss of retinal neurons is not accompanied by any significant loss of Müller (glial) cells. It is noteworthy that the described progressive (and probably irreparable) retinal destructions occur also in the attached retina, and may account for visual impairment in strikingly large areas of the visual field, even after retinal reattachment.     

Effectiveness of interventions to reduce aggression and injuries among ice hockey players: a systematic review

Background:

The increasing incidence of injuries related to playing ice hockey is an important public health issue. We conducted a systematic review to evaluate the effectiveness of interventions designed to reduce injuries related to aggressive acts in ice hockey.

Methods:

We identified relevant articles by searching electronic databases from their inception through July 2012, by using Internet search engines, and by manually searching sports medicine journals, the book series Safety in Ice Hockey and reference lists of included articles. We included studies that evaluated interventions to reduce aggression-related injuries and reported ratings of aggressive behaviour or rates of penalties or injuries.

Results:

We identified 18 eligible studies. Most involved players in minor hockey leagues. Of 13 studies that evaluated changes in mandatory rules intended to lessen aggression (most commonly the restriction of body-checking), 11 observed a reduction in penalty or injury rates associated with rule changes, and 9 of these showed a statistically significant decrease. The mean number of penalties decreased by 1.2–5.9 per game, and injury rates decreased 3- to 12-fold. All 3 studies of educational interventions showed a reduction in penalty rates, but they were not powered or designed to show a change in injury rates. In 2 studies of cognitive behavioural interventions, reductions in aggressive behaviours were observed.

Interpretation:

Changes to mandatory rules were associated with reductions in penalties for aggressive acts and in injuries related to aggression among ice hockey players. Effects of educational and cognitive behavioural interventions on injury rates are less clear. Well-designed studies of multifaceted strategies that combine such approaches are required.Over the last 15 years, the incidence of brain and spinal cord injuries among ice hockey players has increased.¹ A recent study involving players in junior leagues found that, in the 2009/10 hockey season, the incidence of game-related concussions was 7 times higher than the highest rate previously reported in 1998/99.² Brain injuries frequently result from aggressive bodychecking³ and account for 15% of injuries among players 9–16 years of age.^4,5 In a study of a community-based hockey program involving boys aged 9–15 years, hostile aggressive acts, which have an intention to do harm,⁶ were the primary cause of injury in one-third of games in which an injury resulted.⁷ Among high school students in Minnesota who played varsity ice hockey, those who played to relieve aggression were 4 times more likely than other players to experience a concussion.⁸ These findings highlight the association between aggressive behaviour and injury in ice hockey. However, little is known about what can be done to reduce this behaviour to create a safer environment for the sport.Existing reviews about reducing injury in sport have primarily assessed equipment or risk factors associated with injury.^9–11 Recent systematic reviews highlighted the risks of bodychecking and renewed calls for policies to disallow bodychecking among youth playing ice hockey.^3,12 We conducted a systematic review to assess the effectiveness of interventions designed to reduce aggressive acts and related injuries among ice hockey players. We were particularly interested in evaluating the effectiveness of rule changes, educational interventions and behavioural modification in reducing aggressive acts and related injuries.     

Coagulation factors and fibrinolytic system in subretinal liquid in patients with rheumatogenous retinal detachment

The work deals with estimation of some factors of blood coagulation and fibrinolytic systems, which include antithrombin III, factor X, prothrombin, plasminogen, protein C concentrations in the subretinal fluid of the patients with rhegmatogenous retinal detachment retina. The tendency to increase of the blood coagulation and fibrinolysis factor levels, except protein C, was revealed in the patients with complicated forms of the disease. The investigations mentioned above are capable of serving as a diagnostical and forecasting test characterizing the rhegmatogenous retinal detachment retina and surgical treatment proceeding.     

Rhegmatogenous retinal detachment in a patient with choroidal melanoma simulating choroidal detachment: a case report

Background

Ophthalmologists and retina specialists may consider choroidal detachment if patients with rhegmatogenous retinal detachment present with choroidal elevation. That misdiagnosis may lead to inappropriate treatments, development of tumor cell dissemination, and eventual promotion of patient death. We report a case of a patient with rhegmatogenous retinal detachment associated with choroidal melanoma simulating choroidal detachment according to fundus findings.

Case presentation

A 78-year-old Japanese woman with blurred vision in her right eye was referred to our hospital because of rhegmatogenous retinal detachment with complicated atypical choroidal detachment. Her intraocular pressure was normal with clear anterior chamber. Retinal detachment involving the inferior and nasal retina was observed, and a retinal hole was noted in the same quadrant. A small yellowish choroidal elevation was located in the inferonasal site. Gadolinium-enhanced magnetic resonance imaging revealed enhancement corresponding to the elevation, leading to the identification of a choroidal tumor. Enucleation of the patient’s right eye was eventually performed. The enucleated eye histologically demonstrated malignant melanoma.

Conclusions

If hypotony or an inflammatory sign is absent, ophthalmologists should pay attention to the differential diagnosis of choroidal elevations observed in such patients.

     

Disorders of the Menstrual Cycle in Elite Female Ice Hockey Players and Figure Skaters

The purpose of this study was to assess and compare the incidence of delayed menarche and menstrual dysfunction among elite ice hockey players and figure skaters. Forty-three ice hockey players (23.5 ± 4.8 years, 68.2 ± 1.2 kg, 1.68 ± 0.01 m) and 39 figure skaters (17.5 ± 3.4 years, 53.7 ± 5.8 kg, 1.64 ± 0.05 m) completed a self-administered questionnaire on their menstrual status and history, training regimens and lifestyle. Age at menarche did not differ significantly between ice hockey players (13.3 ± 1.3 years) and figure skaters (13.7 ± 1.4 years). Menarche was unrelated to nationality, vigorous training premenarche or age at which the athlete began her sport, but was correlated with the age at menarche of the athletes’ mothers (r = 0.39, p &lt; 0.05). Hormonal contraceptives were used by 35% of ice hockey players and 15% of the figure skaters. Amenorrhea and oligomenorrhea were experienced by 7.1% and 38.7% of postmenarcheal, ice hockey players and figure skaters respectively not using hormonal contraceptives. Menstrual dysfunction was associated with both age and age at menarche in the ice hockey players only. Training factors, and psychological pressure were perceived by the athletes to contribute to menstrual dysfunction. A greater training volume, younger age at commencing sport, lower body mass, greater subjective body image pressure and younger biological and gynaecological age were reported among the figure skaters, and were proposed to explain the higher incidence of menstrual dysfunction among the figure skaters compared with the ice hockey players. Figure skaters appear at increased risk of amenorrhea and oligomenorrhea compared with ice hockey players, which may be linked to training and physical characteristics of the sports.     

Idiopathic uveal effusion syndrome

Idiopathic uveal effusion syndrome (IUES) is a rare condition characterized by a spontaneous detachment of the choroid, often with a secondary non-rhegmatogenous retinal detachment, in healthy middle-aged men. It is hypothesized that the primary cause of the condition is a congenital scleral anomaly causing abnormal uveoscleral protein transport. The following case report reviews a typical presentation of IUES. The patient was treated with lamellar sclerectomy and sclerostomy with resolution of the choroidal detachment over the next several months. Three months later, the patient developed unilateral disswelling and a non-ischemic central retinal vein occlusion which eventually resolved without sequelae.