Characterization of an anterior segment organ culture model for open globe injuries.
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ABSTRACT:
SUBMITTER: Snider EJ
PROVIDER: S-EPMC8058041 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe prognostic significance of debridement has long been demonstrated for trauma in tissues other than ocular. Unfortunately, the impact of wound healing in the anterior segment (AS) was not paid as much attention as in the posterior segment (PS). This study aims to evaluate whether a better prognosis can be obtained from continuous surgical treatment (CST) before fibrosis or scar formation in an open AS injury.MethodsIn this prospective comparative cohort study, 19 eyes of 19 patients with an experience of AS open globe injury (OGI) were selected from the database of the eye injury vitrectomy study (EIVS) from January 1, 2020 to July 31, 2021. Of 19 patients, 9 who received CST were assigned to group 1, and 10 patients without CST after the initial wound repair were included in group 2. Comparison between the two groups was conducted in the final best corrected visual acuity (BCVA). Significant AS complications after injury were evaluated with χ2 test. The corneal leucoma area ratio, astigmatism, and the score of AS abnormalities were analyzed using the Student's t-test.ResultsThe differences of baseline clinical factors between the two groups were not statistically significant. The final BCVA was better in group 1 than in group 2 (P=0.011). The complications directly caused by AS injury, namely adhesive corneal leucoma, uneven anterior chamber, block of light passing through the pupil, and fibrosis or scarring, were more frequent in group 2 than in group 1 (P=0.011, 0.022, 0.037, and 0.040, respectively). Secondary glaucoma (3 cases) and severe AS structure destruction (2 cases) occurred only in group 2 (P=0.037 and 0.474, respectively). The area ratio of leucoma (0.79±0.44, 0.82±0.50, respectively) and corneal astigmatism (3.69±1.90, 4.50±4.80, respectively) revealed no statistical significance between the two groups. On the other hand, the score of AS abnormalities, mean values being 93.33±11.18 for group 1 and 67.00±29.46 for group 2, was statistically different (P=0.022).ConclusionsInitiating CST before fibrosis or scar formation might improve the prognosis of open AS injury, which was preferable to natural wound healing after wound repair.
| S-EPMC10498217 | biostudies-literature
Project description:To determine the effect of transforming growth factor (TGF)-beta2 treatment on intraocular pressure (IOP), outflow facility, and cochlin expression in vitro in monkey and pig organ-cultured anterior segments (MOCAS and POCAS).MOCAS (rhesus and cynomolgus) or POCAS were infused with media containing 10 ng/mL TGFbeta2 to one segment of each pair and 0.1% BSA (vehicle) to the contralateral segment for up to 14 days at a constant rate. Cochlin expression was determined by immunohistochemical study, ELISA, and Western blot analysis using chicken polyclonal antibodies against different regions of cochlin.TGFbeta2 infusion produced elevated IOP in MOCAS (usually after 5 days), that was approximately 45% greater than baseline and compared to control segments. Outflow facility (OF) was decreased by approximately 40% compared with pretreatment baseline (n=5). In POCAS (n=7), IOP was increased (approximately 3 days) by approximately 75% compared with baseline and contralateral changes. The IOP elevation subsided thereafter. Cochlin levels increased with duration of TGFbeta2 treatment in the media and in the region of the trabecular meshwork in both species.TGFbeta2-induced IOP elevation was associated with an increase in cochlin secretion into the media and expression in the tissue of MOCAS and POCAS. Whether cochlin overexpression contributes to elevated IOP or is a consequence of other changes relevant to IOP elevation remains to be determined.
| S-EPMC2680191 | biostudies-literature
Project description:BackgroundGlaucoma is a blinding disease largely caused by dysregulation of outflow through the trabecular meshwork (TM), resulting in elevated intraocular pressure (IOP). We hypothesized that transplanting TM cells into a decellularized, tissue-engineered anterior segment eye culture could restore the outflow structure and function.MethodsPorcine eyes were decellularized with freeze-thaw cycles and perfusion of surfactant. We seeded control scaffolds with CrFK cells transduced with lentiviral vectors to stably express eGFP and compared them to scaffolds seeded with primary TM cells as well as to normal, unaltered eyes. We tracked the repopulation behavior, performed IOP maintenance challenges, and analyzed the histology.ResultsTransplanted cells localized to the TM and progressively infiltrated the extracellular matrix, reaching a distribution comparable to normal, unaltered eyes. After a perfusion rate challenge to mimic a glaucomatous pressure elevation, transplanted and normal eyes reestablished a normal intraocular pressure (transplanted = 16.5 ± 0.9 mmHg, normal = 16.9 ± 0.9). However, eyes reseeded with eGFP-expressing CrFK cells could not regulate IOP, remaining high and unstable (27.0 ± 6.2 mmHg) instead.ConclusionTissue-engineered anterior segment scaffolds can serve as readily available, scalable ocular perfusion cultures. This could reduce dependency on scarce donor globes in outflow research and may allow engineering perfusion cultures with specific geno- and phenotypes.
| S-EPMC10148776 | biostudies-literature
Project description:ImportanceOpen globe injuries can lead to substantial visual morbidity and lifelong sequelae. Interventions to reduce the burden of open globe injuries in the United States require a better understanding of these injuries through well-designed epidemiologic investigations.ObjectiveTo examine the incidence, common injury mechanisms, and economic burden of open globe injuries in the United States.Design, setting, and participantsThis retrospective, cross-sectional study of US nationwide emergency department (ED) data assessed all ED visits of patients with a primary diagnosis of open globe injury in the Nationwide Emergency Department Sample (NEDS) from January 1, 2006, to December 31, 2014. Data analysis was performed from August 29, 2018, to November 11, 2019.Main outcomes and measuresAnnual incidence of open globe injuries by age, sex, mechanism of injury, and concomitant diagnosis, as well as median charges associated with open globe injuries and variables associated with hospitalization.ResultsA total of 124 989 ED visits for open globe injuries were assessed, with an incidence of 4.49 per 100 000 population in the United States from 2006 to 2014 (mean [SD] age of study participants, 37.7 [22.5] years; 94 078 [75.3%] male). The incidence was highest in 2006 (5.88 per 100 000 population) and decreased by 0.3% per month between 2006 and 2014 (incidence rate ratio, 0.99; 95% CI, 0.99-0.99; P < .001). Open globe injuries occurred in 37 060 individuals (30.6%) of low socioeconomic status. The most common injury mechanism was being struck by or against an object or person (40 119 of all 124 989 injury mechanisms [32.1%]). Open globe injuries associated with falls increased 6.6% between 2006-2010 and 2011-2015 (95% CI, 1.04-1.08; P < .001) and were the most common injury mechanism in individuals older than 70 years. The total cost associated with open globe injuries was $793 million. The cost of ED visits increased from $865 during 2006-2010 to $1557 during 2011-2015. Inpatient costs similarly increased from $21 527 during 2006-2010 to $30 243 during 2011-2015.Conclusions and relevanceThe incidence of open globe injuries in the United States decreased from 2006 to 2014. Although the data are from 5 to 13 years ago, these findings appear to provide valuable information for targeting preventive measures toward individuals at highest risk; targeting young men with lower socioeconomic status and individuals 70 years or older at an increased risk of falls may help lower the incidence of open globe injuries.
| S-EPMC6990674 | biostudies-literature
Project description:Assembly of the ocular anterior segment (AS) is a critical event during development of the vertebrate visual system. Failure in this process leads to anterior segment dysgenesis (ASD), which is characterized by congenital blindness and predisposition to glaucoma. The anterior segment is largely formed via a neural crest-derived population, the Periocular Mesenchyme (POM). In this study, we aimed to characterize POM behaviors and transcriptional identities during early establishment of the zebrafish AS. Two-color fluorescent in situ hybridization suggested that early AS associated POM comprise of a heterogenous population. In vivo and time-course imaging analysis of POM distribution and migratory dynamics analyzed using transgenic zebrafish embryos (Tg[foxc1b:GFP], Tg[foxd3:GFP], Tg[pitx2:GFP], Tg[lmx1b.1:GFP], and Tg[sox10:GFP]) revealed unique AS distribution and migratory behavior among the reporter lines. Based on fixed timepoint and real-time analysis of POM cell behavior a comprehensive model for colonization of the zebrafish AS was assembled. Furthermore, we generated single cell transcriptomic profiles (scRNA) from our POM reporter lines and characterized unique subpopulation expression patterns. Based on scRNA clustering analysis we observed cluster overlap between neural crest associated (sox10/foxd3), POM (pitx2) and finally AS specified cells (lmx1b, and foxc1b). scRNA clustering also revealed several novel markers potentially associated with AS development and/or function including lum, fmoda, adcyap1b, tgfbi, and hmng2. Taken together, our data indicates that AS-associated POM, or Anterior Segment Mesenchyme (ASM), is not homogeneous but rather comprised of several subpopulations with differing colonization patterns, migration behavior, and transcriptomic profiles.
| S-EPMC7266958 | biostudies-literature
Project description:To evaluate demographic characteristics and clinical outcomes of work-related open globe injuries in the most industrialized region of Turkey.The demographic and medical records of patients with work-related open globe injuries who presented to the ophthalmology or emergency departments with an official occupational accident report were retrospectively reviewed. Visual acuity categories were defined according to the World Health Organization. The injury types and zones of the open globes were classified according to Birmingham Eye Trauma Terminology System.Among 479 patients with work-related eye injuries in 5 years, there were 102 eyes of 101 patients with open globe injuries (21%). The mean age of the patients was 34.5±8.9 years with a mean follow-up of 12.5±12.6 months. The injuries peaked in June in the hour between 12:00 and 13:00. Eighty-six percent presented to emergency services within 12 hours after the injury. Twenty-two percent of the patients had been wearing protective eyewear at the time of injury. The open globe injuries were penetrating in 51%, intraocular foreign body in 40%, rupture in 7% and perforation in 2% of the eyes. The most frequent finding was traumatic cataract. Final visual acuity of 33.3% of patients was below 3/60. Seventy-eight percent of patients that had visual acuity worse than 6/18 at presentation had visual acuity of 6/18 or better at final visit. Sixty-three percent of eyes which had injuries involving all 3 zones resulted in phthisis bulbi, enucleation or evisceration.Work-related open globe injuries may have severe consequences such as visual impairment and blindness among the young male working population in industrialized areas. Nearly half of the occupational open globe injuries resulted in visual impairment and blindness.
| S-EPMC5282536 | biostudies-other
Project description:This study compares the clinical features and physician selection of either Regional Anesthesia (peribulbar or retrobulbar block) with Monitored Anesthesia Care (RA-MAC) or General Anesthesia (GA) for open globe injury repair.A non-randomized, comparative, retrospective case series at a University Referral Center.All adult repairable open globe injuries receiving primary repair between January 1st, 2004 and December 31st, 2014 (11 years). Exclusion criteria were patients less than 18 years of age and those treated with primary enucleation.Data was gathered via retrospective chart review.Data collected from each patient was age, gender, injury type, location, length of wound, presenting visual acuity, classification of anesthesia used, duration of the procedure performed, months of clinical follow-up, and final visual acuity.During the 11 years study period, 448 patients were identified who had open globe injuries with documented information on zone of injury. Globe injury repair was performed using RA-MAC in 351/448 (78%) patients and general anesthesia in 97/448 (22%) patients. Zone 1, 2 and 3 injuries were recorded in 241, 135, and 72 patients respectively. The rates in specific zones, of RA-MAC versus GA were as follows: Zone 1 - 213/241 (88%) vs 28/241 (12%), Zone 2 - 104/135 (77%) vs 31/135 (23%) and Zone 3 - 34/72 (47%) vs 38/72 (53%). Open globe injuries repaired under RA-MAC had significantly shorter wound length (p<0.001), more anterior wound location (p<0.001) and shorter operative times (p<0.001). RA-MAC cases also had a better presenting and final visual acuity (p<0.001). Neither class of anesthesia conferred a greater visual acuity improvement (p=0.06). The use of GA did not cause any delay in the time elapsed from injury until surgical repair (p=0.74).RA-MAC is a reasonable alternative to GA for the repair of open globe injuries in selected adult patients. RA-MAC was selected more often for Zone 1 and Zone 2 injuries. For eyes with Zone 3 injuries, there are equal selection ratio for RA-MAC and GA.
| S-EPMC5607023 | biostudies-literature
Project description:PurposeTo evaluate the tilt, decentration, and internal higher-order aberrations (HOAs) of sutured posterior-chamber intraocular lenses (IOLs) in patients with open globe injuries.Methods46 consecutive patients (47 eyes) who underwent transsclerally sutured IOL implantation were enrolled in this prospective cohort study. Nineteen eyes had a history of open globe injury. The tilt and decentration of the IOLs and the visual quality were measured 1 month after surgery.ResultsThe horizontal tilt and decentration of the IOLs in the open-globe-injury group were significantly higher than those in the control group (both P < 0.05). In the open-globe-injury group, the horizontal decentration was significantly greater in the limbus-sclera-involved group (n = 11) than in the only-cornea-involved group (n = 8, P = 0.040). The internal coma, 3rd-order, and total HOA values at pupil sizes of 4 mm (P = 0.006) and 6 mm (P = 0.013) were significantly higher in the open-globe-injury group than in the controls. Consequently, the optical quality data for the modulation transfer function and the Strehl ratio (all P < 0.05) were significantly poorer in the open-globe-injury group.ConclusionsOpen globe injuries damage the structural integrity of the eyeball, resulting in more-misaligned sutured IOLs and poorer visual quality.
| S-EPMC5682077 | biostudies-literature
Project description:Hypoxia plays an important role in several retinal diseases, especially in central retinal artery occlusion (CRAO). Although CRAO has been known for over a hundred years, no cure or sufficient treatment is available. Potential therapies are being evaluated in several in vivo models or primary cultures. However, in vivo models or primary cultures are very time-consuming, expensive, and furthermore several therapies or agents cannot be tested. Therefore, we aimed to develop a standardized organotypic ex vivo retinal hypoxia model. A chamber was developed in which rat retinal explants were incubated for different hypoxia durations. Afterwards, the retinas were adjusted to normal air and incubated for 24, 48 or 72 h under standard conditions. To analyze the retinal explants, and in particular the retinal ganglion cells (RGC) immunohistology, western blot and optical coherence tomography (OCT) measurements were performed. To compare our model to a standardized degeneration model, additional retinal explants were treated with 0.5 and 1 mM glutamate. Depending on hypoxia duration and incubation time, the amount of RGCs decreased and accordingly, the amount of TUNEL-positive RGCs increased. Furthermore, β-III-tubulin expression and retinal thickness significantly decreased with longer-lasting hypoxia. The reduction of RGCs induced by 75 min of hypoxia was comparable to the one of 1 mM glutamate treatment after 24 h (20.27% versus 19.69%) and 48 h (13.41% versus 14.41%) of incubation. We successfully established a cheap, standardized, easy-to-use organotypic culture model for retinal hypoxia. We selected 75 min of hypoxia for further studies, as approximately 50% of the RGC died compared to the control group after 48 h.
| S-EPMC5550914 | biostudies-other
Project description:PurposeTo evaluate the effects of intravitreal anti-VEGF agents in a rabbit model of open-globe injury (OGI).MethodsOGI was induced in the right eyes of 75 Belgian rabbits by making 5 mm circumferential incision placed 6 mm behind the limbus. The rabbits were divided into 4 groups: control (n = 5), OGI group (n = 40), and intravitreal Ranibizumab and Conbercept (n = 15 each). Ranibizumab or Conbercept was injected into the vitreous at 0.5 hours, 3 days, or 7 days. Vitreous fluid was collected, and levels of growth factors and cytokines were measured by enzyme-linked immunosorbent assay (ELISA). On day 28 after OGI, B scan examination and histological examination were performed to evaluate intravitreal proliferation and formation of epiretinal fibrosis.ResultsVitreous levels of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), and plasminogen activator inhibitor-1 (PAI-1) were significantly increased in rabbit eyes after OGI. Compared to eyes in OGI group, anti-VEGF treatments significantly reduced these growth factors and cytokines. Among the 7 eyes examined from each group for intravitreal proliferative changes, they were found in 7 of 7 (100%) in OGI group and were decreased by Ranibizumab and Conbercept to 5 of 7 (71.4%) and 4 of 7 (57.1%), respectively. Both Ranibizumab and Conbercept inhibited epiretinal scar formation at the wound site, with Conbercept showing the greatest effect (maximal length of scar (L), L OGI = 503 ± 82.44 μm, L Ranibizumab = 355 ± 43.66 μm, and L Conbercept = 250.33 ± 36.02 μm).ConclusionAnti-VEGF treatments after OGI significantly attenuated the upregulation of growth factors and cytokines in the vitreous and prevented intravitreal proliferation and epiretinal scar formation and thus may protect against the development of posttraumatic complications such as proliferative vitreoretinopathy (PVR).
| S-EPMC8064804 | biostudies-literature