Corneal Burn Research Articles

Dexamethasone acetate loaded poly(ε-caprolactone) nanofibers for rat corneal chemical burn treatment

Topical eye drop approaches to treat ocular inflammation in dry eyes often face limitations such as low efficiency and short duration of drug delivery. Nanofibers serve to overcome the limitation of the short duration of action of topical eye drops used against ocular inflammation in dry eyes. Several attempts to develop suitable nanofibers have been made; however, there is no ideal solution. Here, we developed polycaprolactone (PCL) nanofibers loaded with dexamethasone acetate (DEX), prepared by electrospinning, as a potential ocular drug delivery platform for corneal injury treatment. Thirty-nine Sprague Dawley rats (7 weeks old males) were divided into four treatment groups after alkaline burns of the cornea; negative control (no treatment group); dexamethasone eyedrops (DEX group); PCL fiber (PCL group); dexamethasone loaded PCL (PCL + DEX group). We evaluated therapeutic efficacy of PCL + DEX by examining the epithelial wound healing effect, the extent of corneal opacity and neovascularization. Additionally, various inflammatory factors, including IL-1β, were investigated through immunochemistry, western blot analysis, and quantitative real-time RT-PCR (qRT-PCR). PCL + DEX group showed histologically alleviated signs of corneal inflammation compared with DEX group, which showed a decrease in IL-1β and MMP9 in the corneal stroma. The quantitative expression on day 1 after alkaline burn of pro-inflammatory markers, including IL-1β and IL-6, in the PCL + DEX group was significantly lower than that in the DEX group. Notably, PCL + DEX treatment significantly suppressed neovascularization, and enhanced the anti-inflammatory function of DEX during the acute phase of ocular inflammation. Collectively, these findings suggest that PCL + DEX may be a promising approach to effective drug delivery in corneal burn injuries.

Doxycycline versus Curcumin for Inhibition of Matrix Metalloproteinase Expression and Activity Following Chemically Induced Inflammation in Corneal Cells.

Sulfur mustard (SM) is a potent blistering agent. This alkylating chemical agent has extremely toxic effects on the eye. MMP-2 and MMP-9 are the two most important matrix metalloproteinase enzymes involved in the pathology of chemical eye injuries. Curcumin is regarded as a natural anti-inflammatory agent. This study aims to compare the anti-inflammatory effects of curcumin versus doxycycline on chemically induced corneal injuries. The HCE-2 cell line was used as a model for corneal cells. The effective concentrations of 2-chloroethyl ethyl sulfide (CEES) - as an analog of SM - doxycycline, and curcumin were determined using the MTT assay. The gene expression of MMP-2, MMP-9, and tissue inhibitors of metalloproteinase (TIMP-1) was evaluated by the real-time PCR method. Also, the activity of MMP-2 and MMP-9 enzymes was determined by zymography. The expression of the MMP-2 and MMP-9 genes increased 5- and 3.3-fold after exposure to CEES, respectively. Following the treatment with curcumin and doxycycline, MMP-2 expression decreased significantly. Also, after treatment with curcumin and doxycycline, the MMP-9 expression decreased 2.5- and 1.6-fold, respectively. The reduction in activity was 32% for MMP-2 and 56% for MMP-9 after treatment with curcumin. The corresponding values were 12% and 40% following doxycycline treatment. There was no significant difference between the effects of curcumin and doxycycline on reducing MMP-2 expression, but the difference was statistically significant in the case of MMP-9. Doxycycline and curcumin can inhibit MMP expression and activity in chemically exposed corneal cells. Curcumin has a greater ability than doxycycline to inhibit MMP-2 and MMP-9 enzymes; however, the difference is statistically significant only in the case of MMP-9. After further validation, these substances can be introduced as anti- inflammatory agents to treat corneal chemical burns.

FP7.20 - Peri-orbital burns: A 5-Year Review of the Epidemiological Characteristics and Outcomes at a Regional Burns Centre in the UK 2019 – 2023

Abstract Background Burn injuries are a major cause of global morbidity. Despite being infrequent, peri-orbital and ocular burns can have significant implications on a patient’s vision and overall quality of life. In Northern Ireland, the current epidemiological landscape of peri-orbital burns is not clear. This study aimed at assessing the incidence of peri-orbital and ocular burns and the management outcomes of patients admitted at the regional burns unit in Northern Ireland 2019-2023. Methods Patients admitted to the regional burns unit in Northern Ireland between January 2019 and September 2023 with periorbital burns were identified from the burns unit electronic records, the burns unit database and hospital image database. Results Over 5 years, 100 patients with facial burns were treated, including 60 patients with eyelid burns. 71% were males and 29% were females with a mean age of 47 years. The mean burn size was 14% total body surface area. The burn depth varied; 55% superficial partial thickness, 22% mixed, 17% full thickness and 6% deep dermal. Majority of burns were flame burns 64%. In total, 7 patients sustained corneal burns, one patient responded to steroids, one underwent amniotic membrane grafting, one lost complete vision in both eyes, one had physical debridement and topical antimicrobials and three patients required periorbital reconstruction to maintain eye closure. Conclusion 60% of Facial burns were associated with eyelid burns, the majority of which were caused by flame burns and were managed conservatively with wound cleaning, physical debridement, and application of topical antimicrobials. Despite being rare, complete loss of vision was associated with mortality among our patients.

A chimeric anti-vascularization immunomodulator prevents high-risk corneal transplantation rejection via ex vivo gene therapy

Corneal blindness affects greater than 5 million individuals, with over 180,000 corneal transplantations (CTs) performed annually. Inhigh-risk CTs, almost all grafts are rejected within 10 years. Herein, adeno-associated virus (AAV) ex vivo gene therapy was investigated to establish immune tolerance in the corneal allograft to prevent high-risk CT rejection. Our previous work has demonstrated that HLA-G contributes to ocular immune privilege by inhibiting both immune cells and neovascularization; however, homodimerization is a rate-limiting step for optimal HLA-G function. Therefore, a chimeric protein termed single chain immunomodulator (sclM), was engineered to mimic the native activity of the secreted HLA-G dimer complex and eliminate the need for homodimerization. In a murine corneal burn model, AAV8-sclM significantly reduced corneal vascularization and fibrosis. Next, ex vivo AAV8-scIM gene delivery to corneal allografts was evaluated in a high-risk CT rejection rabbit model. All sclM treated corneas were well tolerated and transparent after 42 days while 83% of vehicle treated corneas were rejected. Histologically, AAV-scIM treated corneas were devoid of immune cell infiltration, vascularization, with minimal fibrosis at the host-graft interface. The data collectively demonstrate that sclM gene therapy prevents corneal neovascularization, reduces trauma-induced corneal fibrosis, and prevents allogeneic CT rejection in a high-risk large animal model.

The Pattern of Corneal Diseases in North Kordofan State

Background: All corneal diseases cause ocular morbidity and decrease vision, or even blindness, so early management intervention is critical. This study sought to evaluate several corneal disorders, including corneal foreign bodies, corneal tears, and ruptured globes. Methodology: This retrospective descriptive study was undertaken in El-Obeid Teaching Hospital's Ophthalmology Emergency Department in North Kordofan State, Sudan, as well as Dr. Khalil's Ophthalmology Center. This study sample, which represents the entire corneal illness, was obtained from 1000 patient files for various eye conditions. Results: This study examines 205 patients with corneal disorders to assess the prevalence of corneal diseases in North Kordofan State. The study found that the disease is more common in males, with 48 out of 78 patients (62%) being male and 38% being female. The male-to-female ratio is 1.6:1. The age group that is most affected is the group of individuals younger than 9 years, accounting for 34% of the affected population. This is followed by the age groups of 10–20 years, 21–32 years, 33–53 years, and >54 years, which account for 24%, 18%, 14%, and 9%, respectively. Regarding the classification of corneal disorders, the most prevalent form is foreign body corneal disease, accounting for 38% of cases. This is followed by corneal tear (16%), corneal opacity (15%), corneal tear with iris prolapses (10%), bacterial corneal ulcer (7%), and rupture globe (6%). The incidence rates of viral corneal ulcers, chemical trauma, burn trauma, and keratoconus are 3%, 3%, 1%, and 1%, respectively. Conclusion: Eye trauma is prevalent in north Kordofan, leading to an upsurge in corneal illnesses including foreign body cornea, corneal tear, and ruptured globe.

BENEFICIAL EFFECTS OF ANGIOSTATIN K1-3 AND LACTOFERRIN IN ALKALI-BURNED RABBIT CORNEA: A COMPARATIVE STUDY

Corneal injury is associated with hypoxia-induced neovascularization, which interferes optical transparency of the cornea, resulting in vision loss and blindness. The treatment of corneal damage remains a ignificant unmet medical need. Lactoferrin (Lf) and angiostatins (AS) are naturally occurring antiinflammatory and antiangiogenic proteins, which play important roles in eye physiology and can be used as protectors against corneal diseases. The aim of the study was to evaluate and compare the effects of plasminogen fragment AS K1-3 and Lf (as a referent preparation) on the levels of the principal markers of angiogenesis, apoptosis, and autophagy in the burn-injured cornea. Additionally, effects of AS on the metabolic activity of macrophages have been studied. Materials and methods. Experimental model of corneal burn was induced by NaOH application to rabbit’s eye surface. One of the group of animals with injured cornea topically received AS, which were applied as eye drops (1 μM solution) daily for 14 days after injury, another one was treated by the equimolar solution of Lf. The levels of protein markers of angiogenesis (VEGF), apoptosis (caspase-3), and autophagy (beclin-1) were evaluated in corneal lysates by western blot. Histological analysis was performed by hematoxylin/eosin staining of corneal slices followed by light microscopy. Effects of AS in the range of concentrations 10-200 nM on the activity of phagocytic cells were assessed in murine macrophage cell line J744.2 by the test with nitroblue tetrazolium (NBT). The quantitative results were analysed with the use of Mann-Whitney U-test. The difference between group mean values was considered significant at P < 0.05. Results. Dramatically increased levels of protein markers related to angiogenesis, apoptosis, and utophagy were found in the corneas with burn-induced injury. AS or Lf-based treatment reduced burninduced overexpression of VEGF, caspase-3, and beclin-1. It is important to note that AS, along with anti-VEGF activity, appeared to more effectively suppress apoptosis and autophagy by decreasing tested markers near the control level, as compared with Lf. Histochemical examination revealed typical signs of fibrotic and necrotic changes in the injured corneas, which were associated with excessive inflammatory infiltration and intense neovascularization. Treatment of burn-induced injury with AS alleviated histopathological changes in cornea, which is evidenced by improving epithelial regeneration, reducing neovascularization, nd moderating leucocyte infiltration. These observations are in agreement with the ata of NBT test suggesting that AS in the concentrations >50 nM is able to moderately inhibit metabolic activity of macrophages up to 30% as compared with intact cells (P<0.05). Conclusions. Obtained results indicate that AS may serve as an effective treatment option to relief alkali-induced corneal injury with the efficacy comparable or even higher than that of firmly established eye protective protein Lf.

Case Report: A rare case of lightning strike causing corneal burn injury

The likelihood of being hit by the likelihood of experiencing lightning within a year was approximately 1 in 960,000. Despite this alarming statistic, it is reassuring to know that the chances of surviving a lightning strike are relatively high; around 90% of people who are struck by lightning manage to survive. Lightning-caused ophthalmic injuries are caused by heat that can be generated through the direct or indirect flow of electric current, and by resistance and shock waves caused by heat. Electrical burn injuries rarely cause ocular complications, since the initial burn is typically fatal. We present a case of lightning injury that affected the eyes. and its treatment and a brief overview of the literature on the subject.

Tamarind seed polysaccharide-metformin insert: Higher ocular retention, slow-release, and efficacy against corneal burn

Metformin (MET) can be an alternative therapeutic strategy for managing ocular burn primarily because of its pleiotropic mechanism. Longer retention on the ocular surface and sustained release are necessary to ensure the efficacy of MET for ocular application. Although the high aqueous solubility of MET is good for formulation and biocompatibility, it makes MET prone to high nasolacrimal drainage. This limits ocular residence and may be a challenge in its application. To address this, polymers approved for ophthalmic application with natural origin were analyzed through in silico methods to determine their ability to bind to mucin and interact with MET. An ocular insert of MET (3 mg/6 mm) was developed using a scalable solvent casting method without using preservatives. The relative composition of the insert was 58 ± 2.06 %w/w MET with approximately 14 %w/w tamarind seed polysaccharide (TSP), and 28 %w/w propylene glycol (PG). Its stability was demonstrated as per the ICH Q1A (R2) guidelines. Compatibility, ocular retention, drug release, and other functional parameters were evaluated. In rabbits, efficacy was demonstrated in the 'corneal alkali burn preclinical model'. TSP showed potential for mucoadhesion and interaction with MET. With adequate stability and sterility, the insert contributed to adequate retention of MET (10–12 h) in vivo and slow release (30 h) in vitro. This resulted in significant efficacy in vivo.

SICS as a procedure for cataract with severe corneal scar: a case report

Introduction : Cataracts are the most common cause of visual impairment and blindness in Indonesia, according to the Rapid Assessment of Avoidable Blindness (RAAB) survey, which is around 70-80% of patients. Meanwhile, corneal disorders are the second cause of blindness after cataract in the world. Incidence of corneal scar in patients with cataracts can exacerbate visual disturbances to cause blindness and require special treatment.
 Case Illustration : A 75 years old woman with blurry eyes since 1 year ago. Acuity of the right eye (OD) was 1/300 and the left eye (OS) was 1/300. Extensive and severe scars were found on the corneas of both eyes. Lens opacities were found in the anterior eye segment. Patient was diagnosed with ODS mature senile cataract and ODS corneal scar. Surgical treatment was carried out using the small-incision cataract surgery (SICS) method, IOL inserted and iridectomy.
 Discussion : Mature cataract patients with advanced age tend to have a denser and harder lens. Cataract extraction performed by phacoemulsification procedure in very dense and hard cataracts requires higher ultrasound energy settings thereby increasing the risk of corneal endothelial trauma and burns which will exacerbate corneal scarring in patients. SICS is a better treatment compared to phacoemulsification in patients with complex situations such as corneal scarring in dense and hard cataracts with minimal surgical complications and optimal results. Iridectomy in cataract surgery can be performed if iris prolapse occurs due to high pressure from the posterior segment of the eye.
 Conclusion : The SICS procedure shows good results for cataract patients with severe corneal scars

Evaluation of the Use of Highly Concentrated Autologous Platelet-Rich Plasma and Platelet-Rich Fibrin Membrane to Improve the Outcome in the Management of Severe Dry Eye Disease, Corneal Neurotrophic Ulcer and Corneal Burn.

The aim of this study was to evaluate the use of highly concentrated platelet-rich plasma (PRP) subconjunctival injections, in combination with eye drops (eye PRP, or E-PRP), in treating dry eye disease (DED) and the use of platelet-rich fibrin (PRF) membrane in treating corneal burns and neurotrophiculcers for the restoration of the homeostasis of the tear film and the morphology and function of the cornea. We studied 16 patients (n=32 eyes) with severe DED. The disease was graded as severe according to the Oxford Grading Scale.There were 12 males (75%) and four females (25%) with a mean age of 56 years; these patients were treated with monotherapy, which involved a single subconjunctival injection of 0.2-0.3 mL of PRP prepared from autologous blood, followed by application of autologous PRP eye drops four times a day for 15 days between September 2019 and December 2020 in the same geographic area. All patients gave written informed consent before undergoing the outlined treatment protocol. We evaluated best corrected visual acuity (BCVA), Schirmer test score, tear film breakup time (TBUT) and corneal staining with fluorescein (Oxford Grading Scale) before and after six to eight weeks of treatment. Subjective normalization was defined by a decrease in the Ocular Surface Disease Index (OSDI) score to 10 or less, an objective normalization of the TBUT to five to six seconds, improvement in the Schirmer test score and Oxford grading and the BCVA gain of at least one line in the vision chart (Snellen chart). Furthermore, we report on the results from different variants of platelet concentrate-based treatments in five cases of corneal diseases: neurotrophic ulcers and corneal burns due to different causes (e.g., chemical burns) using E-PRP and PRF membrane with regard to normalization of morphology and function. The OSDI score decreased to normalization in 75% of the patients (p=6.545× 10-15). TBUT was restored significantly in 20 of 32 eyes from 2.78±0.55 to 5.43±0.71 (p=1.612× 10-24). The Schirmer test score showed an improvement from 4.46±0.67 to 10.28±1.18 (p=3.411 ×10-29), and BCVA improved by 43.75%, from 0.15±0.19 to 0.09±0.16 (logMAR, p=0.2331). Oxford grading changed to Scale I in 75% and Scale 0 in 25% of the patients. No complications or adverse reactions occurred in the five cases of corneal injuries. We observed a restoration of the morphology and function of the cornea with PRP injections or PRF+PRP application in 7-12 days, depending on the severity of the initial finding. PRP treatment is a new approach in ophthalmology with impressive results. Although patients show good compliance and acceptance of the treatment protocol, studies with larger sample sizes are needed to confirm and optimize its use.

Differential diagnostic criteria for chemical corneal burn in dogs and cats and methods of their treatment

The paper presents data on risk factors for the development of chemical burns of the cornea, and presents the most common causes that can cause burn injury to the cornea. The clinical picture of chemical burns of the cornea in dogs and cats is analyzed in detail, differential diagnostic criteria and their prognostic significance are described. A treatment regimen for chemical burns of the cornea is proposed depending on the location and size of the defect. The most common types of chemical reagents that cause corneal burns are household chemicals. The most severe type of burn is the one that affects the limbal zone, leading to the development of limbal cell insufficiency and, as a consequence, more severe complications. The proposed treatment regimen for chemical burns of the cornea, based on the size and location of the defect, has shown its effectiveness and consistency. With timely treatment, taking into account the clinical picture, and a prognosis based on it, it is possible to save not only the eyeball as an organ, but also to achieve complete restoration of the morphofunctional characteristics of the cornea.

Basic mechanisms and clinical implications of ocular surface inflammation

Basic mechanisms and clinical implications of ocular surface inflammation.The pathopyhsiology of ocular surface inflammation is complex and involves a number of actors. Beside the immune system, a key role is emerging for the vasculature (both blood and lymph vessels), central and peripheral nervous system. From the old dogma of a cornea completely devoided of immune cells, a lot has been learned about how leukocytes, neurons and vessels interact and how imbalances in their function(s) may affect the onset and outcome of blinding diseases such as corneal burns or ocular graft versus host disease.

Modulating neuroinflammation to restore vision

Corneal inflammation is a common feature in most diseases of the eye, including rare eye diseases. Specifically, it has a key role in dry eye, infectious keratitis and after surgery. While the immune system was originally considered the master generator of the inflammatory response, the role of the nervous system (both central and peripheral) in regulating immune activation has finally emerged. Specifically, the role of neurotransmitters and neruopeptides in exacerbating, or modulating, the inflammatory response has been described. These recents findings have shed light on novel mechanisms which can be exploited therapeutically for the treatment of blinding ocular diseases, such as aniridia, graft versus host disease, or corneal burns.

Chemical Corneal Burn After Short Exposure to Alcohol-Containing Chlorhexidine Antiseptic

Chlorhexidine is used routinely for asepsis in craniofacial surgeries. A solution containing a lower concentration of chlorhexidine diluted with alcohol has been developed to decrease chlorhexidine-related side effects. Herein, we report a case of chemical corneal burn caused by hexitanol solution (2% chlorhexidine + 72% ethanol) in a patient after undergoing closed reduction for nasal fracture under general anesthesia. Although the presumptive exposure time of the cornea was short, slit-lamp examination revealed epithelial defects. The patient received conservative care with extensive saline irrigation and conservative treatment with 0.3% gatifloxacin, 1% prednisolone, and carbomer eye drops. Among the various antiseptic solutions, ethanol markedly decreases cell viability in a concentration-dependent manner by inducing cell lysis, even after short exposure. Moreover, chlorhexidine induces corneal toxicity, necessitating corneal transplantation. Therefore, surgeons should be aware of the complications associated with the use of chlorhexidine or alcohol-containing antiseptics and the use povidone for its low ocular toxicity.

Chemical Burn Injury on the Cornea Following Skin Preparation With Chlorhexidine in Tonsillectomy and Adenoidectomy.

This article report discusses a pediatric patient who suffered a corneal chemical burn injury after tonsillectomy and adenoidectomy surgery due to skin preparation with chlorhexidine. In this case, inadequate sealing of the eye shield during skin preparation allowed the chlorhexidine-alcohol solution to accumulate at its edge and gradually penetrate, resulting in the corneal injury. Prompt ophthalmological intervention and appropriate eye care treatment led to a gradual improvement in the patient's symptoms. The authors aim to present the case, share the revisions made to our skin preparation policy, and emphasize the importance of cautious antiseptic use to minimize the risk of adverse events. Adverse effects of chlorhexidine, such as hypersensitivity reactions and burns, including corneal damage, are highlighted. Health care providers should exercise caution when selecting and applying antiseptics, considering patient-specific factors, and comprehensive training should be provided to promote adherence to safe antiseptic practices during surgical procedures.

Nonlinear fourth-order elastic characterization of the cornea using torsional wave elastography

Measuring the mechanical nonlinear properties of the cornea remains challenging due to the lack of consensus in the methodology and in the models that effectively predict its behaviour. This study proposed developing a procedure to reconstruct nonlinear fourth-order elastic properties of the cornea based on a mathematical model derived from the theory of Hamilton et al. and using the torsional wave elastography (TWE) technique. In order to validate its diagnostic capability of simulated pathological conditions, two different groups were studied, non-treated cornea samples (n=7), and ammonium hydroxide (NH4OH\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$NH_4OH$$\\end{document}) treated samples (n=7). All the samples were measured in-plane by a torsional wave device by increasing IOP from 5 to 25 mmHg with 5 mmHg steps. The results show a nonlinear variation of the shear wave speed with the IOP, with higher values for higher IOPs. Moreover, the shear wave speed values of the control group were higher than those of the treated group. The study also revealed significant differences between the control and treated groups for the Lamé parameter μ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\mu$$\\end{document} (25.9–6.52 kPa), third-order elastic constant A (215.09–44.85 kPa), and fourth-order elastic constant D (523.5–129.63 kPa), with p-values of 0.010, 0.024, and 0.032, respectively. These findings demonstrate that the proposed procedure can distinguish between healthy and damaged corneas, making it a promising technique for detecting diseases associated with IOP alteration, such as corneal burns, glaucoma, or ocular hypertension.

Pax6-Induced Proliferation and Differentiation of Bone Marrow Mesenchymal Stem Cells Into Limbal Epithelial Stem Cells.

Corneal integrity, transparency, and visual acuity are maintained by corneal epithelial cells (CECs), which are continuously renewed by limbal epithelial stem cells (LESCs). The limbal stem cell deficiency is associated with ocular diseases. This study aimed to develop a novel method to differentiate bone marrow mesenchymal stem cells (BM-MSCs) into LESC-like cells using a culture medium and paired box 6 (Pax6) transfection. The LESC-like cells were confirmed using the LESC markers CK14 and p63 and CEC marker CK12. Pax6 induces BM-MSCs to differentiate into LESC-like cells in vitro. Mouse models of chemical corneal burn were obtained and treated with the LESC-like cells. The transplantation experiment indicated that Pax6-reprogrammed BM-MSCs attached to and replenished the damaged cornea through the formation of stratified corneal epithelium. The proliferation and colony formation abilities of Pax6-overexpressing BM-MSCs were significantly enhanced. These findings provide evidence that BM-MSCs might serve as an excellent candidate for generating bioengineered corneal epithelium and provide a new strategy for the treatment of clinical corneal damage.

A Rational Design of Metal–Organic Framework Nanozyme with High-Performance Copper Active Centers for Alleviating Chemical Corneal Burns

HighlightsInspired by metalloenzymes with well-defined coordination structures, a series of Cu-X metal–organic frameworks (MOFs) nanozymes with tunable copper active centers were successfully constructed.Experimental and theoretical results strongly supported that precisely tuning the coordination of halogen atoms could directly regulate the enzyme-like activities of Cu-X MOFs by influencing their spatial configuration and electronic structure.The optimal Cu–Cl MOF with excellent enzyme-mimicking activities could effectively relieve ocular chemical burns by possible antioxidant and antiapoptotic mechanisms.

Lens extraction versus laser peripheral iridotomy for acute primary angle closure.

Lens extraction versus laser peripheral iridotomy for acute primary angle closure.

Salubrinal Ameliorates Inflammation and Neovascularization via the Caspase 3/Enos Signaling in an Alkaline-Induced Rat Corneal Neovascularization Model.

Background and Objectives: Ocular alkaline burn is a clinical emergency that can cause permanent vision loss due to limbal stem cell deficiency and corneal neovascularization (CNV). Although the basic pathogenetic mechanisms are considered to be acute oxidative stress and corneal neovascularization triggered by inflammation, the underlying intracellular mechanisms have not been clearly elucidated. The aim of this study was to investigate the role of endoplasmic reticulum (ER) stress on inflammation and neovascularization, and the effect of the ER stress inhibitor salubrinal (SLB), as a novel treatment in a corneal alkaline burn model in rats. Methods: Chemical burns were created by cautery for 4 s using a rod coated with 75% silver nitrate and 25% potassium nitrate in the corneal center for the corneal neovascularization (CNV) model. Twenty-eight Wistar albino rats were divided into four groups: SHAM, CNV, CNV + SLB, and CNV + bevacizumab (BVC). After the CNV model was applied to the right eye, a single subconjunctival dose (0.05 mL) of 1 mg/kg salubrinal was injected into both eyes in the CNV + SLB group. A total of 1.25 mg/mL of subconjunctival BVC was administered to the CNV + BVC group. Fourteen days after experimental modeling and drug administration, half of the globes were placed in liquid nitrogen and stored at -20 °C until biochemical analysis. The remaining tissues were collected and fixed in 10% buffered formalin for histopathological and immunohistochemical analysis. Three qualitative agents from three different pathways were chosen: TNFR for inflammation, endothelial nitric oxide synthase (e-NOS) for vascular endothelial growth factor (VEGF)-mediated vascular permeability, and caspase-3 for cellular apoptosis. Results: Significantly lower caspase-3 and eNOS levels were detected in the CNV + SLB and CNV + BVC groups than in the CNV group. Additionally, histopathological evaluation revealed a significant decrease in neovascularization, inflammatory cell infiltration, and fibroblast activity in the CNV + SLB and CNV + BVC groups. The endoplasmic reticulum stress inhibitor, salubrinal, administered to the treatment group, attenuated apoptosis (caspase-3) and inflammation (e-NOS). In the control group (left eyes of the SLB group), salubrinal did not have a toxic effect on the healthy corneas. Conclusion: The ER stress pathway plays an important role in angiogenesis after alkaline corneal burns, and treatment with SLB modulates this pathway, reducing caspase-3 and eNOS levels. Further studies are needed to understand the molecular mechanisms altered by SLB-mediated therapy. The fact that more than one mechanism plays a role in the pathogenesis of CNV may require the use of more than one molecule in treatment. SLB has the potential to affect multiple steps in CNV pathogenesis, both in terms of reducing ER stress and regulating cellular homeostasis by inhibiting the core event of integrated stress response (ISR). Therefore, it can be used as a new treatment option and as a strengthening agent for existing treatments. Although blockade of intracellular organelle stress pathways has shown promising results in experimental studies, more in-depth research is needed before it can be used in routine practice. To the best of our knowledge, this study is the first to report the role of ER stress in corneal injury.