Endothelial Zmiz1 modulates physiological and pathophysiological angiogenesis during retinal development.

Angiogenesis is a highly coordinated process involving the control of various endothelial cell behaviors. Mechanisms for transcription factor involvement in the regulation of endothelial cell dynamics and angiogenesis have become better understood, however much remains unknown, especially the role of non-DNA binding transcriptional cofactors. Here, we show that Zmiz1, a transcription cofactor, is enriched in the endothelium and critical for embryonic vascular development, postnatal retinal angiogenesis, and pathological angiogenesis in oxygen induced retinopathy (OIR). In mice, endothelial cell-specific deletion of Zmiz1 during embryogenesis led to lethality due to abnormal angiogenesis and vascular defects. Inducible endothelial cell-specific ablation of Zmiz1 postnatally resulted in impaired retinal vascular outgrowth, decreased vascular density, and increased vessel regression. In addition, angiogenic sprouting in the superficial and deep layers of the retina was markedly reduced. Correspondingly, vascular sprouting in fibrin bead assays was significantly reduced in the absence of Zmiz1, while further in vitro and in vivo evidence also suggested deficits in EC migration. In agreement with the defective sprouting angiogenesis phenotype, gene expression analysis of isolated retinal endothelial cells revealed downregulation of tip-cell enriched genes upon inactivation of Zmiz1. Lastly, our study suggested that endothelial Zmiz1 is critical for intraretinal revascularization following hypoxia exposure in the OIR model. Taken together, these findings begin to define the previously unspecified role of endothelial Zmiz1 in physiological and pathological angiogenesis.

Zmiz1 is a novel regulator of lymphatic endothelial cell gene expression and function.

Zinc Finger MIZ-Type Containing 1 (Zmiz1), also known as ZIMP10 or RAI17, is a transcription cofactor and member of the Protein Inhibitor of Activated STAT (PIAS) family of proteins. Zmiz1 is critical for a variety of biological processes including vascular development. However, its role in the lymphatic vasculature is unknown. In this study, we utilized human dermal lymphatic endothelial cells (HDLECs) and an inducible, lymphatic endothelial cell (LEC)-specific Zmiz1 knockout mouse model to investigate the role of Zmiz1 in LECs. Transcriptional profiling of ZMIZ1-deficient HDLECs revealed downregulation of genes crucial for lymphatic vessel development. Additionally, our findings demonstrated that loss of Zmiz1 results in reduced expression of proliferation and migration genes in HDLECs and reduced proliferation and migration in vitro. We also presented evidence that Zmiz1 regulates Prox1 expression in vitro and in vivo by modulating chromatin accessibility at Prox1 regulatory regions. Furthermore, we observed that loss of Zmiz1 in mesenteric lymphatic vessels significantly reduced valve density. Collectively, our results highlight a novel role of Zmiz1 in LECs and as a transcriptional regulator of Prox1, shedding light on a previously unknown regulatory factor in lymphatic vascular biology.

Role of Temporomandibular Total Joint Replacement in Correction of Facial Deformities.

Introduction: Individuals suffering from facial deformities experience esthetic, functional and social setback in their lives every day. These patients benefit greatly with single-stage temporomandibular joint replacement along with orthognathic surgical procedures to correct functional as well as esthetic components. Methodology: Five individuals with facial deformities due to hemifacial macrosomia, fibrous dysplasia, idiopathic condylar resorption, ankylosis, etc., were treated with total joint replacement along with orthognathic surgical procedures for functional and esthetic correction. The customized temporomandibular joint was digitally custom designed, and the orthognathic procedures were virtually planned on NemoFAB software before performing the surgical procedure. Results: Intraoperatively, the overall time was reduced considerably with minimal unpredictable complications. One-week postoperative computed tomographs were obtained and superimposed on preoperative virtual surgical planning which showed minimal discrepancy. Follow-up period of 18-30 months was maintained for all the patients with stable results, minimal relapse and satisfactory functional abilities. Discussion: Total joint replacement along with orthognathic procedure provides single-stage functional and esthetic corrections for the patients, considerably improving their quality of life. Precise preoperative surgical planning proves to be an indispensable step for achieving desired results with minimal margin of error and avoid any unseen complications during the surgical procedure.

Retrospective case-control study to compare exoskeleton-assisted walking with standard care in subacute non-traumatic brain injury patients.

BACKGROUND: Advanced technologies are increasingly used to address impaired mobility after neurological insults, with growing evidence of their benefits for various populations. However, certain robotic devices have not been extensively investigated in specific conditions, limiting knowledge about optimal application for healthcare. OBJECTIVE: To compare effectiveness of conventional gait training with exoskeleton-assisted walking for non-traumatic brain injury during early stage rehabilitation. METHODS: Clinical evaluation data at admission and discharge were obtained in a retrospective case-control design. Patients received standard of care physical therapy either using Ekso GT or not. Within- or between-group statistical tests were performed to determine change over time and interventional differences. RESULTS: This study analyzed forty-nine individuals (33% female), 20 controls and 29 Ekso participants who were equivalent at baseline. Both groups improved in Functional Independence Measure scores and ambulation ability (p < .00001 and p < .001, respectively). Control subjects demonstrated significantly different distance walked and assistance level values at discharge from those who were treated with the exoskeleton (p < .01). CONCLUSION: Robotic locomotion is non-inferior for subacute functional recovery after non-traumatic brain injury. Conventional therapy produced larger gait performance gains during hospitalization. Further research is needed to understand specific factors influencing efficacy and the long-term implications after rehabilitation.

COVID-19-Induced Encephalopathy: A Case Report.

While COVID-19 is known to cause common neurological manifestations such as loss of taste and smell, headaches, and myalgias, rare and severe neurological complications can also occur. We describe the hospitalization of a middle-aged Caucasian woman who presented with altered mental status and an absence of moderate-severe pulmonary symptoms. The patient tested positive for COVID-19 and experienced a tonic-clonic seizure six days after admission. Diagnostic testing, including cerebrospinal fluid analysis, blood cultures, urine cultures, brain imaging, and electroencephalograms were unremarkable, indicating a global encephalopathic state. This case highlights the need for clinicians to anticipate neurological complications when managing patients with COVID-19, especially when respiratory symptoms are minimal or absent. Moreover, further research on COVID-19-induced encephalopathy is crucial to improve patient outcomes and inform clinical practice.

Zmiz1 is a novel regulator of lymphatic endothelial cell gene expression and function.

Zinc Finger MIZ-Type Containing 1 (Zmiz1), also known as ZIMP10 or RAI17, is a transcription cofactor and member of the Protein Inhibitor of Activated STAT (PIAS) family of proteins. Zmiz1 is critical for a variety of biological processes including vascular development. However, its role in the lymphatic vasculature is unknown. In this study, we utilized human dermal lymphatic endothelial cells (HDLECs) and an inducible, lymphatic endothelial cell (LEC)-specific Zmiz1 knockout mouse model to investigate the role of Zmiz1 in LECs. Transcriptional profiling of Zmiz1-deficient HDLECs revealed downregulation of genes crucial for lymphatic vessel development. Additionally, our findings demonstrated that loss of Zmiz1 results in reduced expression of proliferation and migration genes in HDLECs and reduced proliferation and migration in vitro. We also presented evidence that Zmiz1 regulates Prox1 expression in vitro and in vivo by modulating chromatin accessibility at Prox1 regulatory regions. Furthermore, we observed that loss of Zmiz1 in mesenteric lymphatic vessels significantly reduced valve density. Collectively, our results highlight a novel role of Zmiz1 in LECs and as a transcriptional regulator of Prox1, shedding light on a previously unknown regulatory factor in lymphatic vascular biology.

Spectrin-Based Regulation of Cardiac Fibroblast Cell-Cell Communication.

Cardiac fibroblasts (CFs) maintain the fibrous extracellular matrix (ECM) that supports proper cardiac function. Cardiac injury induces a transition in the activity of CFs to promote cardiac fibrosis. CFs play a critical role in sensing local injury signals and coordinating the organ level response through paracrine communication to distal cells. However, the mechanisms by which CFs engage cell-cell communication networks in response to stress remain unknown. We tested a role for the action-associated cytoskeletal protein ßIV-spectrin in regulating CF paracrine signaling. Conditioned culture media (CCM) was collected from WT and ßIV-spectrin deficient (qv4J) CFs. WT CFs treated with qv4J CCM showed increased proliferation and collagen gel compaction compared to control. Consistent with the functional measurements, qv4J CCM contained higher levels of pro-inflammatory and pro-fibrotic cytokines and increased concentration of small extracellular vesicles (30-150 nm diameter, exosomes). Treatment of WT CFs with exosomes isolated from qv4J CCM induced a similar phenotypic change as that observed with complete CCM. Treatment of qv4J CFs with an inhibitor of the ßIV-spectrin-associated transcription factor, STAT3, decreased the levels of both cytokines and exosomes in conditioned media. This study expands the role of the ßIV-spectrin/STAT3 complex in stress-induced regulation of CF paracrine signaling.

A Novel Method to Rehabilitate Post-mucormycosis Maxillectomy Defect by Using Patient-Specific Zygoma Implant.

Aim: During second wave of COVID pandemic, India faced heavy surge of mucormycosis. Treatment option for these patients included either total or partial maxillectomy with primary closure. Rehabilitation of these patients became challenging because of their age and size of defect. The purpose of the present study is to present a new digital technique for the fabrication of patient-specific zygoma implants (PSI) and to report on its survival and complication rates. Material and Methods: Total 21 patients who had undergone either partial or total maxillectomy after mucormycosis and who were disease-free clinically and radiographically for 6 or more months post-resection were rehabilitated using patient-specific zygoma implant. CT scan was obtained for all patients post-maxillectomy for evaluation of existing bone condition. Exocad software was used for virtual surgical planning of zygoma implant considering surgical and prosthetic technicality to achieve goal of maximum functionality and sustainability. Result: All the patients were followed up after 15, 30, 45 and 90 days and there after every month for evaluation of soft tissue healing, infection, dehiscence, loosening of prosthesis, eating efficiency and aesthetic. Follow-up period for all 15 patients was in the range of 6-12 months. Conclusion: In case of post-mucor maxillectomy patients, use of PSI offers the advantages of minimal bone augmentation, reduction in time required to restore lost function, and reduced financial burden of multiple procedures. Therefore, PSI may represent a valid alternative treatment for the prosthetic restoration of post-mucor maxillectomy patients.

An Adolescent Girl with Acute-on-Chronic Abdominal Pain.

We present an 11-year-old pediatric patient with acute-on-chronic abdominal pain found to have a large intra-abdominal abscess with a concomitant dermoid cyst. Acute-on-chronic abdominal pain has one of the broadest and, in our case, ever-changing differential diagnoses. Exploratory laparoscopy revealed a severe pelvic inflammatory process with a large abscess and extensive omental and bowel adhesions, a left ovarian cyst, a shortened appendix with thickened tip, and purulent fluid in the cul-de-sac. These findings suggested a ruptured appendix leading to a large abscess with adjacent ovarian dermoid cyst, and an appendectomy was performed. Our patient responded well to continued intravenous antibiotics, and her drain was removed on the day of discharge. She was sent home with an additional 2 weeks of oral cefdinir and metronidazole. Follow-up ultrasound showed dramatic cyst resolution, and no further intervention was needed. [Pediatr Ann. 2023;52(1):e36-e38.].

Endothelial cell polarity and extracellular matrix composition require functional ATP6AP2 during developmental and pathological angiogenesis.

The (Pro)renin receptor ([P]RR), also known as ATP6AP2, is a single-transmembrane protein that is implicated in a multitude of biological processes. However, the exact role of ATP6AP2 during blood vessel development remains largely undefined. Here, we use an inducible endothelial cell-specific (EC-specific) Atp6ap2-KO mouse model to investigate the role of ATP6AP2 during both physiological and pathological angiogenesis in vivo. We observed that postnatal deletion of Atp6ap2 in ECs results in cell migration defects, loss of tip cell polarity, and subsequent impairment of retinal angiogenesis. In vitro, Atp6ap2-deficient ECs similarly displayed reduced cell migration, impaired sprouting, and defective cell polarity. Transcriptional profiling of ECs isolated from Atp6ap2 mutant mice further indicated regulatory roles in angiogenesis, cell migration, and extracellular matrix composition. Mechanistically, we provided evidence that expression of various extracellular matrix components is controlled by ATP6AP2 via the ERK pathway. Furthermore, Atp6ap2-deficient retinas exhibited reduced revascularization in an oxygen-induced retinopathy model. Collectively, our results demonstrate a critical role of ATP6AP2 as a regulator of developmental and pathological angiogenesis.

The Impact of the Colonoscopy Starting Position and Its Potential Outcomes.

Based on the literature review, many studies have been inconclusive in regards to adenoma detection and procedural positioning during a colonoscopy. Scope looping can make cecal intubation challenging, changing the positioning of the patient and application of external abdominal pressure can overcome this difficulty. A colonoscopy in a prone position can overcome these challenges and reduce cecal intubation time. It can thus improve the safety of the patient and the staff by minimizing the movement of a sedated patient.

Current Treatment Strategies for the Management of the Internal Derangements of the Temporomandibular Joint: A Global Perspective.

Internal joint derangement is a disruption of the internal aspects of the TMJ-disc displacements/adhesions/impingements, causing alterations in the normal dynamic motions of the joint. Clinicians must be diligent in establishing the correct diagnosis and cause of TMJID, which ultimately leads to the appropriate management of such patients. While many patients adapt over time or with non-surgical treatment, surgery may be indicated for those with ongoing problems. The surgical pyramid provides a stepwise progression for TMJ surgical patients. This paper aims to review TMJID and its management with special emphasis on arthroscopic minimally invasive surgery, as practised in other countries around the world, and compare this to current education, understanding and practice in India. Currently, India is lagging behind in providing the full scope of TMJ services as there are very few surgeons trained in the skill of arthroscopic techniques. There needs to be continued expansion of our understanding of TMJID treatment in India to bring it level with the rest of the world.

Cannabis and Its Potential Protective Role Against Inflammatory Bowel Disease: A Scoping Review.

Globally, around 15%-40% of patients suffering from inflammatory bowel disease (IBD) use Cannabis for pain reduction, increased appetite, and reduced need for other medications. Although many patients report having benefited by using Cannabis in IBD, there is still a lack of consensus regarding the use of Cannabis in IBD. The aim is to identify, explore and map literature on the potential protective role of Cannabis against IBD through this scoping review. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed during the search to answer the focal question: (1) Does Cannabis play a protective role against IBD as assessed by clinical remission; (2) If yes, what is the mechanism of action for this protective role. There were only three randomized controlled trials (RCTs) and three observational studies that satisfied the selection criteria of this scoping review. Although promising results including the improvement in general well-being/ Harvey-Bradshaw Index, health perception enhancement [4.1±1.43 to 7±1.42 (p = 0.0002)], weight gain, Crohn's Disease Activity Index (CDAI) score<150, Mayo scores (4-10), and reduction in clinical complications have been found in some studies, its medical use in IBD is still questionable due to the lack of high-quality evidence. Future RCTs studies should determine the cannabis treatment parameters and validate its safety and effectiveness in the IBD setting. The highlights include: the current literature provides inconclusive evidence concerning the protective role of cannabis for IBD patients; limited research evidence regarding the therapeutic use of cannabinoids for IBD warrants future investigation via RCTs; cannabis provides some benefits to IBD patients by improving their general well-being perceptions, Harvey-Bradshaw Index, Mayo scores, and minimizing their clinical complications.

Ca2+/calmodulin kinase II-dependent regulation of ßIV-spectrin modulates cardiac fibroblast gene expression, proliferation, and contractility.

Fibrosis is a pronounced feature of heart disease and the result of dysregulated activation of resident cardiac fibroblasts (CFs). Recent work identified stress-induced degradation of the cytoskeletal protein ßIV-spectrin as an important step in CF activation and cardiac fibrosis. Furthermore, loss of ßIV-spectrin was found to depend on Ca2+/calmodulin-dependent kinase II (CaMKII). Therefore, we sought to determine the mechanism for CaMKII-dependent regulation of ßIV-spectrin and CF activity. Computational screening and MS revealed a critical serine residue (S2250 in mouse and S2254 in human) in ßIV-spectrin phosphorylated by CaMKII. Disruption of ßIV-spectrin/CaMKII interaction or alanine substitution of ßIV-spectrin Ser2250 (ßIV-S2254A) prevented CaMKII-induced degradation, whereas a phosphomimetic construct (ßIV-spectrin with glutamic acid substitution at serine 2254 [ßIV-S2254E]) showed accelerated degradation in the absence of CaMKII. To assess the physiological significance of this phosphorylation event, we expressed exogenous ßIV-S2254A and ßIV-S2254E constructs in ßIV-spectrin-deficient CFs, which have increased proliferation and fibrotic gene expression compared with WT CFs. ßIV-S2254A but not ßIV-S2254E normalized CF proliferation, gene expression, and contractility. Pathophysiological targeting of ßIV-spectrin phosphorylation and subsequent degradation was identified in CFs activated with the profibrotic ligand angiotensin II, resulting in increased proliferation and signal transducer and activation of transcription 3 nuclear accumulation. While therapeutic delivery of exogenous WT ßIV-spectrin partially reversed these trends, ßIV-S2254A completely negated increased CF proliferation and signal transducer and activation of transcription 3 translocation. Moreover, we observed ßIV-spectrin phosphorylation and associated loss in total protein within human heart tissue following heart failure. Together, these data illustrate a considerable role for the ßIV-spectrin/CaMKII interaction in activating profibrotic signaling.

Emerging therapeutic targets for cardiac arrhythmias: role of STAT3 in regulating cardiac fibroblast function.

Introduction : Cardiac fibrosis contributes to the development of cardiovascular disease (CVD) and arrhythmia. Cardiac fibroblasts (CFs) are collagen-producing cells that regulate extracellular matrix (ECM) homeostasis. A complex signaling network has been defined linking environmental stress to changes in CF function and fibrosis. Signal Transducer and Activator of Transcription 3 (STAT3) has emerged as a critical integrator of pro-fibrotic signals in CFs downstream of several established signaling networks. Areas covered : This article provides an overview of STAT3 function in CFs and its involvement in coordinating a vast web of intracellular pro-fibrotic signaling molecules and transcription factors. We highlight recent work elucidating a critical role for the fibroblast cytoskeleton in maintaining spatial and temporal control of STAT3-related signaling . Finally, we discuss potential opportunities and obstacles for therapeutic targeting of STAT3 to modulate cardiac fibrosis and arrhythmias. Relevant publications on the topic were identified through Pubmed. Expert opinion : Therapeutic targeting of STAT3 for CVD and arrhythmias presents unique challenges and opportunities. Thus, it is critical to consider the multimodal and dynamic nature of STAT3 signaling. Going forward, it will be beneficial to consider ways to maintain balanced STAT3 function, rather than large-scale perturbations in STAT3 function.

Urinary Tract Infection in Febrile Children with Sickle Cell Disease Who Present to the Emergency Room with Fever.

Sickle cell disease (SCD) patients are thought to be at higher risk for urinary tract infections (UTIs) compared to the general population secondary to increased sickling, abnormal urinary acidification, and an inability to concentrate the urine. The incidence of UTI in febrile children with SCD in the United States is unknown. Our objectives were to determine the rate of UTI among febrile SCD children and describe the risk factors for UTI in this population. We conducted a retrospective chart review of all febrile SCD patients <4 years of age who presented to a pediatric emergency department from 2012-2017 and who had a sterile sample of urine for analysis. A total of 167 febrile patients with SCD with 464 visits were identified. The majority were African American (95.2%), female (58.7%), and had hemoglobin SS (HbSS) (65.3%). The rate of UTI was 4.1%. All patients with a UTI were African American females with a median age of 19 months (IQR 12-30). On regression analysis, no risk factors were associated with a UTI. We found the rate of UTI in febrile young children with SCD was comparable to non-SCD children. Larger studies are required to identify the presence of risk factors for UTI in this population.

Upper Gastrointestinal Bleed in a Young Male- A Rare Presentation of Eosinophilic Gastroenteritis.

Eosinophilic gastroenteritis (EGE) is a rare idiopathic disease affecting multiple organs (stomach and small intestine) of the digestive tract. It is characterized by eosinophilic infiltration of the bowel wall to a variable depth and symptoms associated with gastrointestinal tract disease. The prevalence of this condition is ranging from 8 and 28 per 100,000. We present a rare presentation of EGE manifesting as upper GI bleeding.  A 28-year-old male with PMH of EGE, duodenal ulcers, and stricture presented to the hospital with the chief complaints of three episodes of dizziness and melena over one day. His home medications included prednisone, montelukast, and pantoprazole. On admission, he was found to be tachycardic (150) while other vital signs were stable. Physical examination revealed cold, pale and clammy skin but was otherwise normal on examination. Initial labs showed hemoglobin (hgb) of 9.3. His hospital course was complicated with 1 episode of large volume hematemesis >1.5 L and brief loss of consciousness for which a code rapid response was called. On day 2, the hgb dropped to 5.7 and the patient received a blood transfusion. Emergent endoscopy (EGD) revealed high-grade duodenal stenosis, severe pyloroduodenal deformity and a duodenal ulcer with the visible vessel. Two clips were deployed blindly. Epinephrine could not be injected due to hard and fibrotic tissue around duodenal stenosis. The Interventional Radiology team was consulted and emergent angiography was done which revealed active bleeding from a branch of the gastric artery. Embolization was done and hemostasis was achieved successfully. He needed 5 units of PRBC transfusion in total. He was treated with pantoprazole twice a day intravenously since admission. For his known duodenal stricture, the surgical team was consulted. No acute surgical intervention was recommended. On discharge, he was sent home with pantoprazole 40 mg twice a day, slow tapering of prednisone and close follow up with gastroenterology, surgery, and primary care doctor within 1 week. The purpose of this case report is to increase awareness about this clinical condition among medical professionals.

Fibroblast growth factor-inducible 14 mediates macrophage infiltration in heart to promote pressure overload-induced cardiac dysfunction.

AIMS: Heart failure (HF) is characterized by compromised cardiac structure and function. Previous work has identified a link between upregulation of pro-inflammatory cytokines and HF. Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a pro-inflammatory cytokine, which binds to fibroblast growth factor inducible 14 (Fn14), a ubiquitously expressed cell-surface receptor. The objective of this study was to investigate the role of TWEAK/Fn14 pathway in promoting cardiac inflammation under non ischemic stress conditions. MAIN METHODS: Wild type (WT) and Fn14 knock out (Fn14-/-) mice were subjected to pressure overload [transaortic constriction (TAC)] for 1 or 6 weeks. A subset of WT TAC animals were treated with the Fn14 antagonist L524-0366. Cardiac function was measured by echocardiography. Cardiac fibrosis and macrophage infiltration were quantified using immunohistochemistry and flow cytometry, respectively. Cardiac fibroblasts were isolated for quantifying TWEAK-induced chemokine release. KEY FINDINGS: Fn14-/- mice displayed improved cardiac function, reduced fibrosis and lower macrophage infiltration in heart compared to WT following TAC. L524-0366 mitigated maladaptive remodeling with TAC. TWEAK induced secretion of the pro-inflammatory chemokine, monocyte chemoattractant protein 1 from WT but not Fn14-/- fibroblasts in vitro, in part through activation of non-canonical NF-κB signaling. Finally, Fn14 expression was increased in mouse following TAC and in human failing hearts. SIGNIFICANCE: Our findings support an important role for the TWEAK/Fn14 promoting macrophage infiltration and fibrosis in heart under non-ischemic stress, with potential for therapeutic intervention to improve cardiac function in the setting of HF.

Annexin A3 is necessary for parallel artery-vein alignment in the mouse retina.

BACKGROUND: Annexin A3 (Anxa3) is a member of the calcium-regulated, cell membrane-binding family of annexin proteins. We previously confirmed that Anxa3 is expressed in the endothelial lineage in vertebrates and that loss of anxa3 in Xenopus laevis leads to embryonic blood vessel defects. However, the biological function of Anxa3 in mammals is completely unknown. In order to investigate Anxa3 vascular function in mammals, we generated an endothelial cell-specific Anxa3 conditional knockout mouse model (Anxa3f/f ;Tie2-Cre). RESULTS: Anxa3f/f ;Tie2-Cre mice are born at Mendelian ratios and display morphologically normal blood vessels during development. However, loss of Anxa3 leads to artery-vein (AV) misalignment characterized by atypical AV crossovers in the postnatal and adult retina. CONCLUSIONS: Anxa3 is not essential for embryonic blood vessel formation but is required for proper parallel AV alignment in the murine retina. AV crossovers associated with Anxa3f/f ;Tie2-Cre mice are similar to AV intersections observed in patients with branch retinal vein occlusion (BRVO), although we did not observe occluded vessels. This new Anxa3 mouse model may provide a basis for understanding AV crossover formation associated with BRVO.