Fibrotic Membrane Research Articles

An mRNA-encoded dominant-negative inhibitor of transcription factor RUNX1 suppresses vitreoretinal disease in experimental models.

Messenger RNA (mRNA)-based therapies are a promising approach to medical treatment. Except for infectious diseases, no other disease has mRNA-based therapies available. The eye is an ideal model for mRNA therapeutic development because it requires limited dosing. Proliferative vitreoretinopathy (PVR) is a blinding condition caused by retinal detachment that now lacks available medical treatment, with surgery as the only treatment option. We previously implicated runt-related transcription factor-1 (RUNX1) as a driver of epithelial-to-mesenchymal transition (EMT) in PVR and as a critical mediator of aberrant ocular angiogenesis when up-regulated. On the basis of these findings, an mRNA was designed to express a dominant-negative inhibitor of RUNX1 (RUNX1-Trap). We show that RUNX1-Trap delivered in polymer-lipidoid complexes or lipid nanoparticles sequestered RUNX1 in the cytosol and strongly reduced proliferation in primary cell cultures established from fibrotic membranes derived from patients with PVR. We assessed the preclinical efficacy of intraocular delivery of mRNA-encoded RUNX1-Trap in a rabbit model of PVR and in a laser-induced mouse model of aberrant angiogenesis often used to study wet age-related macular degeneration. mRNA-encoded RUNX1-Trap suppressed ocular pathology, measured as pathological scores in the rabbit PVR model and leakage and lesion size in the laser-induced choroidal neovascularization mouse model. mRNA-encoded RUNX1-Trap also strongly reduced proliferation in a human ex vivo explant model of PVR. These data demonstrate the therapeutic potential of mRNA-encoded therapeutic molecules with dominant-negative properties, highlighting the potential of mRNA-based therapies beyond standard gene supplementation approaches.

Role of semaphorin7A in epithelial-mesenchymal transition and proliferative vitreoretinopathy

Proliferative vitreoretinopathy (PVR) is a multifactorial ocular condition characterized by the development of fibrotic membranes inside the vitreous cavity and on the detached retina, which can result in severe blindness. Semaphorin7A (Sema7a) is involved in axon growth, inflammatory responses, and immune regulation; however, its role in PVR and regulatory mechanisms in retinal pigment epithelium (RPE) cells remains unclear. This study aimed to examine Sema7a in PVR and the underlying mechanisms. Transcriptome sequencing was used to investigate the changes in mRNA expression profiles. Western blotting, immunofluorescence, and real-time polymerase chain reaction (RT-PCR) were utilized to investigate the potential mechanism of Sema7a on epithelial-mesenchymal transition (EMT) in RPE cells. Stimulating RPE cells with transforming growth factor beta-1 (TGF-β1) decreased the levels of epithelial markers but increased those of mesenchymal markers. Based on transcriptome sequencing, many molecules associated with PVR progression were regulated. PVR vitreous fluid proteomics data analysis showed that Sema7a significantly changed at different levels. Silencing Sema7a in RPE cells attenuated TGF-β1-induced EMT and their ability to induce experimental PVR; in contrast, recombinant Sema7a (rSema7a) directly triggered EMT in RPE cells. TGF-β1 induction mechanically activated the PI3k-AKT and MAPK pathways, while Sema7a knockdown by short interfering RNA lowered the phosphorylation of the PI3k-AKT/MAPK signaling pathway. Therefore, Sema7a may be a viable therapeutic target for PVR due to its crucial role in the TGF-β1-induced EMT of RPE cells.

Proliferative Vitreoretinopathy in Retinal Detachment: Perspectives on Building a Digital Twin Model Using Nintedanib.

Proliferative vitreoretinopathy (PVR) is a pathological process characterized by the formation of fibrotic membranes that contract and lead to recurrent retinal detachment. Pars plana vitrectomy (PPV) is the primary treatment, but recurrence rates remain high, as surgery does not address the underlying molecular mechanisms driving fibrosis. Despite several proposed pharmacological interventions, no approved therapies exist, partly due to challenges in conducting preclinical and in vivo studies for ethical and safety reasons. This review explores the potential of computational models and Digital Twins, which are increasingly gaining attention in medicine. These tools could enable the development of progressively complex PVR models, from basic simulations to patient-specific Digital Twins. Nintedanib, a tyrosine kinase inhibitor targeting PDGFR, VEGFR, and FGFR, is presented as a prototype for computational models to simulate its effects on fibrotic pathways in virtual patient cohorts. Although still in its early stages, the integration of computational models and Digital Twins offers promising avenues for improving PVR management through more personalized therapeutic strategies.

Abdominal Cocoon: a rare case of small bowel obstruction, a case report

Sclerosing encapsulating peritonitis (SEP), or abdominal cocoon syndrome (ACS), is an uncommon disorder marked by a thick fibrotic membrane that completely or partially envelops the small bowel. For surgeons, preoperative diagnosis is difficult and challenging. The majority of documented, diagnosis were made during a laparotomy. We present a case of SEP that was diagnosed preoperatively. The patient had a complete small bowel obstruction that necessitated urgent surgery. We review the literature and discuss the causes, clinical manifestation, and management of the condition.

Preclinical characterization of endotoxin-induced uveitis models using OCT, PET/CT and proteomics

Uveitis is a group of inflammatory ocular pathologies. Endotoxin-Induced Uveitis (EIU) model represent a well-known model induced by administration of Lipopolysaccharide (LPS). The aim is to characterize two models of EIU through two routes of administration with novel noninvasive imaging techniques. 29 rats underwent Intraocular Pressure (IOP) measurements, Optical Coherence Tomography (OCT), proteomic analysis, and Positron Emission Tomography and Computed Tomography (PET/CT). Groups included healthy controls (C), BSS administered controls (Ci), systemically induced EIU with LPS (LPSs), and intravitreally induced EIU with LPS (LPSi) for IOP, OCT, and proteomic studies. For 18F-FDG PET/CT study, animals were divided into FDG-C, FDG-LPSs and FDG-LPSi groups and scanned using a preclinical PET/CT system. LPSi animals exhibited higher IOP post-induction compared to C and LPSs groups. LPSi showed increased cellular infiltrate, fibrotic membranes, and iris inflammation. Proinflammatory proteins were more expressed in EIU models, especially LPSi. PET/CT indicated higher eye uptake in induced models compared to FDG-C. FDG-LPSi showed higher eye uptake than FDG-LPSs but systemic uptake was higher in FDG-LPSs due to generalized inflammation. OCT is valuable for anterior segment assessment in experimental models. 18F-FDG PET/CT shows promise as a noninvasive biomarker for ocular inflammatory diseases. Intravitreal induction leads to higher ocular inflammation. These findings offer insights for future inflammatory disease research and drug studies.

Bone morphogenetic protein 6 (BMP6) antagonises experimental proliferative vitreoretinopathy established by TGF-β2 stimulation in retinal pigment epithelial cells through modulation of the p38 and JNK MAPK pathways.

The formation of the epiretinal fibrotic membrane by retinal pigment epithelial (RPE) cells is a primary pathological change for proliferative vitreoretinopathy (PVR). Bone morphogenetic protein 6 (BMP6) is an antifibrogenic factor in various cells. To date, it is still unknown whether BMP6 can interfere with the fibrogenesis of RPE cells during the progression of PVR. This work aimed to address the relationship between BMP6 and transforming growth factor-β2 (TGF-β2)-elicited fibrogenesis of RPE cells, an experimental model for studying PVR in vitro. The BMP6 level was down-regulated, while the TGF-β2 level was up-regulated in the vitreous humor of PVR patients. The BMP6 level was down-regulated in human RPE cells challenged with TGF-β2. The treatment of RPE cells with TGF-β2 resulted in significant increases in proliferation, migration, epithelial-to-mesenchymal transition (EMT), and extracellular matrix (ECM) remodelling. These effects were found to be inhibited by the overexpression of BMP6 or exacerbated by the knockdown of BMP6. BMP6 overexpression reduced the phosphorylation of p38 and JNK in TGF-β2-stimulated RPE cells, while BMP6 knockdown showed the opposite effects. The inhibition of p38 or JNK partially reversed the BMP6-silencing-induced promoting effects on TGF-β2-elicited fibrogenesis in RPE cells. Taken together, BMP6 demonstrates the ability to counteract the proliferation, migration, EMT, and ECM remodelling of RPE cells induced by TGF-β2. This is achieved through the regulation of the p38 and JNK MAPK pathways. These findings imply a potential connection between BMP6 and PVR, and highlight the potential application of BMP6 in therapeutic interventions for PVR.

Transition to Chronic Fibrosis in an Animal Model of Retinal Detachment With Features of Proliferative Vitreoretinopathy.

Proliferative vitreoretinopathy (PVR) is the most common cause of failure of surgically repaired rhegmatogenous retinal detachment (RRD). Chemically induced and cell injection PVR models do not fully simulate the clinical characteristics of PVR in the post-RRD context. There is an unmet need for translational models in which to study mechanisms and treatments specific to RRD-PVR. RRD was induced in adult Dutch Belted rabbits. Posterior segments were fixed or processed for RNA sequencing at 6 hours and 2, 7, 14, and 35 days after induction. Histochemical staining and immunolabeling for glial fibrillary acidic protein, alpha smooth muscle actin, vascular endothelial growth factor receptor 2, CD68, and RPE 65 kDa protein were performed, and labeling intensity was scored. Single cell RNA sequencing was performed. Acute histopathological changes included intravitreal and intraretinal hemorrhage, leukocytic vitritis, chorioretinitis, and retinal rarefaction. Chronic lesions showed retinal atrophy, gliosis, fibrotic subretinal membranes, and epiretinal fibrovascular proliferation. Fibrillar collagen was present in the fibrocellular and fibrovascular membranes in chronic lesions. Moderate to strong labeling of glia and vasculature was detected in chronic lesions. At day 14, most cells profiled by single cell sequencing were identified as Mϋller glia and microglia, consistent with immunolabeling. Expression of several fibrillar collagen genes was upregulated in chronic lesions. Histological and transcriptional features of this rabbit model simulate important features of human RRD-PVR, including the transition to chronic intraretinal and periretinal fibrosis. This animal model of RRD with features of PVR will enable further research on targeted treatment interventions.

Effects of Apelin on the fibrosis of retinal tissues and Müller cells in diabetes retinopathy through the JAK2/STAT3 signalling pathway

Retinal fibrosis was a key characteristic of diabetes retinopathy (DR). Apelin was found to be a candidate for tissue fibrosis. Nevertheless, the role of Apelin in the Müller cells in DR remains unclear. This study identified the function and mechanism of Apelin in Müller cells and the fibrosis of retinal tissue. Western blot was carried out to detect the Apelin, GFAP, Collagen I, α-SMA, JAK2 and STAT3 protein levels. Masson staining was performed to display the histopathological changes in retinal tissue of diabetic mellitus (DM) rats. The immunofluorescence staining was conducted to evaluate the Apelin levels in the retinal tissue. The levels of GFAP, Collagen I and α-SMA in the retinal tissue of DM rats was visualised by the immunohistochemistry staining. The results showed that Apelin, GFAP, Collagen I andα-SMA expression was prominently elevated in the retinal tissue of DM rats and high glucose (HG)-exposed Müller cells. The results of Masson staining showed that the epiretinal fibrotic membrane was observed in DM rats. Apelin knockdown declined the GFAP, Collagen I andα-SMA levels. Besides, the protein levels of p-JAK2 and p-STAT3 were elevated in the HG-treated Müller cells, while Apelin knockdown declined them. FLLL32 treatment neutralised the role of Apelin. In conclusion, Apelin facilitated the fibrogenic activity of Müller cells through activating the JAK2/STAT3 signalling pathway, and thus inducing the retinal fibrosis in DR.

Aberrant Akt2 signaling in the RPE may contribute to retinal fibrosis process in diabetic retinopathy

Diabetic Retinopathy (DR) is a complication of diabetes that causes blindness in adults. Retinal fibrosis is closely associated with developing proliferative diabetic retinopathy (PDR). Clinical studies have shown that fibrotic membranes exhibit uncontrolled growth in PDR and contribute to retinal detachment from RPE cells, ultimately leading to vision loss. While anti-VEGF agents and invasive laser treatments are the primary treatments for PDR, retinal fibrosis has received minimal attention as a potential target for therapeutic intervention. Therefore, to investigate the potential role of Akt2 in the diabetes-induced retinal fibrosis process, we generated RPE-specific Akt2 conditional knockout (cKO) mice and induced diabetes in these mice and Akt2fl/fl control mice by intraperitoneal injection of streptozotocin. After an 8-month duration of diabetes (10 months of age), the mice were euthanized and expression of tight junction proteins, epithelial–mesenchymal transition (EMT), and fibrosis markers were examined in the RPE. Diabetes induction in the floxed control mice decreased levels of the RPE tight junction protein ZO-1 and adherens junction proteins occludin and E-cadherin; these decreases were rescued in Akt2 cKO diabetic mice. Loss of Akt2 also inhibited diabetes-induced elevation of RNA and protein levels of the EMT markers Snail/Slug and Twist1 in the RPE as compared to Akt2fl/fl diabetic mice. We also found that in Akt2 cKO mice diabetes-induced increase of fibrosis markers, including collagen IV, Connective tissue growth factor (CTGF), fibronectin, and alpha-SMA was attenuated. Furthermore, we observed that high glucose-induced alterations in EMT and fibrosis markers in wild-type (WT) RPE explants were rescued in the presence of PI3K and ERK inhibitors, indicating diabetes-induced retinal fibrosis may be mediated via the PI3K/Akt2/ERK signaling, which could provide a novel target for DR therapy.

Shen Shuai II Recipe inhibits hypoxia-induced glycolysis by preserving mitochondrial dynamics to attenuate kidney fibrosis.

Shen Shuai II Recipe (SSR) is a traditional Chinese medicine prescription with significant clinical efficacy in chronic kidney disease (CKD) by invigorating Qi and resolving blood stasis, clearing away heat and dampness. Our previous studies demonstrated that SSR attenuated renal interstitial fibrosis (RIF) by improving hypoxia and mitochondrial dysfunction. The aim of this study was to investigate the potential mechanisms of SSR against RIF. The CKD was established by 5/6 ablation/infarction (A/I) operation. After 4 weeks, rats were gavaged with SSR or Fenofibrate for 8 weeks. Hypoxia-treated NRK-52E cells were treated with SSR and (or) glycolysis inhibitors, including GSK2837808A (GSK) and 2-Deoxy-D-glucose (2-DG). In addition, Drp1-deficient or MFP-M1-treated NRK-52E cells were treated with SSR under hypoxic conditions. The effects of SSR on fibrotic phenotype, glycolysis, mitochondrial dynamics and membrane potential in hypoxia-exposed NRK-52E cells were examined by immunoblotting, colorimetric, and fluorometric methods. Furthermore, we constructed a lactic acid-induced activation model of NRK-49F cells and a co-culture system. The activation of NRK-49F cells was evaluated by immunoblotting method. Our findings indicated that SSR significantly attenuated abnormal glycolysis in vivo and in vitro, which was correlated with its renoprotective effect. Further studies revealed that improvement of mitochondrial dynamics could be one of the mechanisms by which SSR inhibits glycolysis to achieve anti-renal fibrosis. Furthermore, treatment with SSR significantly inhibited the lactic acid-induced activation of NRK-49F cells. The co-culture results further highlighted that SSR inhibited activation of renal fibroblasts and deposition of extracellular matrix by reducing glycolysis in renal tubular cells. SSR alleviates RIF by inhibiting hypoxia-induced glycolysis through improvement of mitochondrial dynamics.

The technique and its role of dacryoendoscopy in the management of the false passage of the lacrimal drainage system

This is a retrospective study of patients with primary acquired nasolacrimal duct obstruction (PANDO) who underwent dacryoendoscopy (FT-203F; Fibertech Co., Tokyo, Japan) and sheath-guided silicone intubation for 830 cases with PANDO from March 2016 to December 2020. 19 cases (2.3%) were observed as false passage in the lacrimal drainage system (LDS). Dacryoendoscopic findings revealed that the following factors were associated with LDS obstruction (% cases): structural change of 63.2% (stenosis, 42.1%; fibrotic membrane, 21.1%), and secretory change of 36.8% (mucus, 15.8%; stone, 10.5%; and granulation, 10.5%). The obstruction sites were distributed through LDS. The false passages detected in LDS were managed as follow: usage of fluid irrigation pressure to check the true passage following the previously intubated silicone tube as a reference, and confirmation the end of passage through the inferior meatus with nasal endoscopy. The overall success rate was 73.7% using this management technique. Dacryoendoscopy enables real-time observation of the lumen of the LDS, thus facilitating management of pathological lesions including false passages. With this technique, we are better able to make customized treatment of patients with false passages, with a safer and more effective results leading to the success of dacryoendoscopy guided silicone tube intubation in PANDO patients.

Idiopathic encapsulating peritoneal sclerosis: a case report

Idiopathic encapsulating peritonitis sclerosis is a rare cause of small bowel obstruction. It is diagnosed by the presence of dense white fibrotic membrane encasing a part or the entire small bowel. Diagnosis is usually made intraoperatively and the treatment is usually surgical. We report a case of 16 years old female with idiopathic encapsulating peritoneal sclerosis who presented with the features of recurrent intestinal obstruction. Surgical excision of the fibrotic sac and adhesiolysis was done.

Dacryoendoscopic Findings of Patients with Lacrimal Drainage Obstruction Associated with Cancer Treatment.

To compare the diagnosis and treatment outcome of lacrimal drainage obstruction of patients who underwent systemic chemotherapy (CTx) or radioactive iodine treatment (RAI) by using dacryoendoscopy and at the same time performing dacryoendoscopy-guided silicone tube insertion (STI) to treat epiphora. From July 2017 to December 2020, the medical records of 11 patients (16 eyes) were diagnosed with lacrimal drainage obstruction after CTx or RAI and underwent dacryoendoscopy-guided STI were reviewed retrospectively. We tried to count the number of obstructive sites in total patients using slit-lamp examination and dacryoendoscopic findings. A total of 11 patients, 16 eyes, were enrolled in this study. The onset of epiphora in the CTx group (3.0 ± 4.0 months) was significantly shorter than that in the RAI group (52.6 ± 36.5 months, p = 0.001). There were total 32 obstructive sites including 28 obstructive sites of dacryoendoscopic findings and four sites of punctual stenosis in total 16 cases. Using dacryoendoscopy, granulation findings was dominant in RAI patients (p = 0.038) and mucus finding was frequent mostly in lacrimal sac and canaliculus. In the CTx group, mucosal edema finding was dominant (p = 0.038) and fibrotic membrane finding was frequent in all levels of lacrimal drainage system. Regarding the obstructive location, lacrimal sac was the most frequently obstructed site in the two groups (p = 0.038). The onset of epiphora in the CTx group was significantly earlier than in the RAI group. In the CTx group, mucosal edema finding was frequent in all levels of lacrimal drainage system. In the RAI group, granulation finding was frequent mostly in lacrimal sac and canaliculus. Since the clinical outcome was satisfactory, intervention with dacryoendoscopy-guided STI could be a treatment of choice in patients with epiphora after CTx or RAI.

Novel insights into the pathophysiology of proliferative vitreoretinopathy: The role of vitreoschisis-induced vitreous cortex remnants.

We previously hypothesized a causal relationship between vitreoschisis-induced vitreous cortex remnants (VCR) and the development of proliferative vitreoretinopathy (PVR). This study aims to substantiate this association through histopathological analysis of surgical specimens in support of strategies to improve therapeutic outcomes. A descriptive, prospective, non-consecutive case series. Histopathological and immunohistochemical analyses were performed on membranes removed from the peripheral retinal surface during initial vitrectomy for primary rhegmatogenous retinal detachment (RRD) (n = 11) or recurrent retinal detachment (n = 12). The clinical aspect of the membranes ranged from loose-meshed membranes visualized with triamcinolone to more fibrotic membranes stained with trypan blue. Consistent with the clinical presentation, histopathological analysis revealed membranes with different area characteristics. Paucicellular lamellar collagen-rich areas, suggestive of VCR, appeared to transition to areas of increased cellularity and eventually more fibrotic areas of low cellularity. Five different area characteristics could be identified that seemed to correspond to five histopathological stages in PVR formation, with lamellar VCR collagen acting as an essential precondition: 1. Lamellar collagen, low cellularity (hyalocytes). 2. Lamellar collagen, increased cellularity (hyalocytes, glial cells). 3. Lamellar collagen, high cellularity (macrophages, glial cells, RPE-cells). 4. Early fibrosis, decreased cellularity (myofibroblasts). 5. Fibrosis, low cellularity (myofibroblasts). These findings confirm the role of VCR in preretinal PVR formation posterior to the vitreous base. We propose that the presence of VCR over the retinal surface should be qualified as a risk factor for PVR formation. Detection and adequate removal of VCR may improve the success rate of vitreoretinal surgeries.

Transvitreal Feeder Vessel Ligation and En Bloc Resection of a Retinal Capillary Hemangioblastoma

This video illustrates a healthy 24-year-old female with a one-year history of vision loss in her right eye due to a total tractional-rhegmatogenous retinal detachment associated with a large retinal capillary hemangioblastoma (RCH). Because the lesion and its overlying fibrotic membranes mechanically impeded retinal reattachment, decision was made to perform pars plana vitrectomy (PPV) with tumor resection. While diathermy of the feeder vessels can be done in this scenario, we opted instead for suture ligation to optimize intraoperative hemostasis.

Karaciğer Apsesinin İlk ve Tek Bulgusu Olarak Klebsiella Endoftalmisi

This report aimed to present an endogenous endophthalmitis case occurred as an embolic complication of a liver abscess without any signs other than ocular symptoms. A 58-year-old man was admitted to ophthalmology clinic due to acute onset severe pain and loss of vision in the left eye. With no history of any ocular trauma or surgery, the patient underwent a thorough evaluation including blood sampling, cultures, and abdominal imaging as per the recommendations of the consultation to general surgery department. Computed tomography revealed a hepatic abscess, and an ultrasonography guided drainage was performed for treatment. The purulent drainage fluid culture was positive for Klebsiella pneumoniae. Ocular infection was managed by intravitreal antibiotic and steroid injections in addition to topical fortified and intravenous antibiotic therapy. After medical therapy, a vitrectomy was performed for the sequel such as fibrotic membranes but there was no improvement in the vision.

Transcanalicular endoscopic dacryoplasty in patients with primary acquired nasolacrimal duct obstruction.

To investigate the lacrimal drainage system (LDS) from the punctum to the inferior meatus and the clinical outcomes of transcanalicular endoscopic dacryoplasty and silicone intubation through dacryoendoscopy in patients with primary acquired nasolacrimal duct obstruction (PANDO). We conducted a retrospective chart review of 203 cases from 156 patients who underwent dacryoendoscopy (FT-203F; Fibertech Co., Tokyo, Japan) and sheath-guided silicone intubation for PANDO from December 2014 to March 2018. Clinical characteristics, tear meniscus height, irrigation test, dacryocystographic findings, and dacryoendoscopic findings related to clinical factors and surgical outcomes were evaluated. The study population consisted of 44 males and 119 females (mean age, 60.4 ± 13.6 years). The mean epiphora duration was 3.8 ± 4.8 years. Dacryoendoscopic findings revealed that the following factors were associated with LDS obstruction (% cases): mucus, 39.9%; fibrotic membrane, 19.2%; stones, 9.4%; granulation, 8.9%; and stenosis, 2.7%. The locations of obstruction were as follows (% cases): nasolacrimal duct, 35.7%; canaliculus, 33.0%; sac, 27.6%; and inferior meatus, 3.5%. The types of LDS obstruction were classified into two groups: secretory group (n = 118) that included mucus, stones, and granulation, and structural group (n = 85) associated with the membrane and stenosis; the pattern of them was divided into focal (n = 134) and diffuse (n = 76). The overall success rate was 86.2%. The success rate of the structural group (95.3%) was significantly higher than that of the secretory group (79.7%) (p = 0.001). All membranous obstruction cases at the inferior meatus were treated successfully, regardless of the irrigation test results. The success rate of the focal group (93.1%) was significantly higher than that of the diffuse group (74.0%) (p = 0.003). Dacryoendoscopic findings were informative regarding the clinical factors leading to LDS in PANDO patients. Mucus and stones in the lacrimal sac were common findings of functional lacrimal duct obstruction. Membranous obstruction and stenosis could be managed by recanalization under direct visualization. Transcanalicular endoscopic dacryoplasty and silicone intubation is considered to be a safe and effective procedure, sparing the patient from bony destruction in selected cases of PANDO.

Lenticular fungal infection caused by Aspergillus in a patient with traumatic corneal laceration: a case report

BackgroundTo report a case of lenticular infection caused by Aspergillus, which was diagnosed 13 weeks after traumatic corneal laceration.Case presentationA 60-year-old woman presented with traumatic corneal laceration including anterior lens capsule rupture and traumatic cataract after being hit with a chestnut in the right eye. There were multiple injuries due to tiny thorns of the chestnut, including the conjunctiva, sclera, cornea, and anterior lens capsule. But no visible foreign body was detected by slit-lamp examination. Topical corticosteroid was prescribed to resolve the conjunctival inflammation induced by the thorns of chestnut, which could have caused persistent irritation. As conjunctival injection and edema being decreased during outpatient clinical follow-up, embedded conjunctival foreign body was detected and surgically removed (1st surgery). Approximately 10 weeks after the trauma, severe inflammation of the anterior segment accompanied with hypopyon developed suddenly and at the same time embedded scleral foreign body was revealed. After removal of scleral foreign body (2nd surgery), unspecified mold species was cultured from the scleral foreign body in SDA (Sabouraud dextrose agar) plate. Suspicious corneal foreign body was removed as 3rd surgery and phacoemulsification of traumatic cataract was planned as 4th surgery. Aspergillus was finally detected from removed anterior capsule and fibrotic membrane during the operation. Fungal infection resolved successfully after administration of topical (1% voriconazole and 5% natamycin) and systemic (fluconazole) antifungal agents and phacoemulsification of traumatic cataract.ConclusionChestnut thorns can damage multiple ocular tissues simultaneously. Lens capsular rupture could result in fungal inoculation and lead to delayed lenticular fungal infection with complicated cataract formation. In cases of ocular trauma due to organic substances such as thorns and branches, the possibility of fungal infection should be considered.

Gremlin in the Vitreous of Patients with Proliferative Diabetic Retinopathy and the Downregulation of Gremlin in Retinal Pigment Epithelial Cells.

Diabetic retinopathy (DR) is one of the most common causes of blindness globally. Proliferative DR (PDR), an advanced stage of DR, is characterized by the formation of fibrotic membranes at the vitreoretinal interface. The proliferation, migration, and secretion of extracellular matrix molecules in retinal pigment epithelial (RPE) cells contribute to the formation of fibrotic membranes in PDR. Gremlin has been reported to be upregulated in response to elevated glucose levels in the retina of diabetic rat and bovine pericytes. However, the role of gremlin in PDR remains unclear. In the present study, the vitreous concentrations of gremlin were significantly higher in the PDR (67.79 ± 33.96) group than in the control (45.31 ± 12.31) group, and high glucose levels induced the expression of gremlin in RPE cells. The elevated expression of extracellular matrix molecules, such as fibronectin and collagen IV, was significantly reduced by gremlin siRNA in human RPE cells under high-glucose conditions. Thus, gremlin may play a vital role in the development of PDR.

Gremlin mediates the TGF-β-induced induction of profibrogenic genes in human retinal pigment epithelial cells.

Proliferative vitreoretinopathy (PVR) is characterised by the contraction and growth of fibrotic membranes on the retina and within the vitreous body. Retinal pigment epithelial (RPE) cells, a major cellular component of the fibrotic membrane, is one of the cell types that have been previously reported to associate with PVR pathogenesis. During PVR, RPE cells undergo increased cell proliferation, migration and the secretion of extracellular matrix molecules, such as fibronectin and type I collagen. A variety of cytokines and growth factors are involved in the formation of the fibrotic membrane. Although gremlin has been reported to serve an important role in the regulation of epithelial-to-mesenchymal transition in PVR, the relationship between gremlin and the expression of profibrogenic factors in human RPE cells remains unclear. In the present study, gremlin promoted RPE cell proliferation and the expression of type I collagen and fibronectin. In addition, knocking down gremlin expression by siRNA significantly suppressed the transforming growth factor (TGF)-β1- and TGF-β2-induced expression of type I collagen and fibronectin in RPE cells. These findings suggest that gremlin may serve an important role in the development of PVR.