The microRNA Let-7f Induces Senescence and Exacerbates Oxidative Stress in Retinal Pigment Epithelial Cells.

This study aims to investigate the role of microRNA let-7f in the dysfunction and degeneration of retinal pigment epithelium (RPE) cells through the induction of senescence and oxidative stress. Furthermore, we explore whether let-7f inhibition can protect these cells against sodium iodate (SI)-induced oxidative stress. Oxidative stress and let-7f expression are reciprocally regulated in retinal pigment epithelial cells. Overexpression of let-7f in ARPE-19 cells induced oxidative stress as demonstrated by increased reactive oxygen species (ROS) production as well as senescence. Inhibition of let-7f successfully protected RPE cells from the detrimental effects induced by SI. In addition, let-7f overexpression induced RPE cellular dysfunction by diminishing their migratory capabilities and reducing the phagocytosis of porcine photoreceptor outer segments (POS). Results were further confirmed in vivo by intravitreal injections of SI and let-7f antagomir in C57BL/6 mice. Our results provide strong evidence that let-7f is implicated in the dysfunction of RPE cells through the induction of senescence and oxidative injury. These findings may help to uncover novel and relevant processes in the pathogenesis of dry AMD.

Modulating the Nature of Ionizable Lipids and Number of Layers in Hyaluronan-Decorated Lipid Nanoparticles for In Vitro Delivery of RNAi.

Lipid nanoparticles (LNPs) have established their position as nonviral vectors for gene therapy. Tremendous efforts have been made to modulate the properties of LNPs to unleash their full clinical potential. Among the strategies being pursued, the layer-by-layer (LbL) technique has gained considerable attention in the biomedical field. Illuminated by our previous work, here we investigate if the LbL approach could be used to modify the LNP cores formulated with three different ionizable lipids: DODMA, MC3, and DODAP. Additionally, we wondered if more than three layers could be loaded onto LNPs without disrupting their gene transfection ability. Taking advantage of physicochemical analysis, as well as uptake and gene silencing studies, we demonstrate the feasibility of modifying the surface of LNPs with the LbL assembly. Precisely, we successfully modified three different LNPs using the layer-by-layer strategy which abrogated luciferase activity in vitro. Additionally, we constructed a 5×-layered HA-LNP containing the MC3 ionizable lipid which outperformed the 3×-layered counterpart in transfecting miRNA-181-5p to the pediatric GBM cell line, as a proof-of-concept in vitro experiment. The method used herein has been proven reproducible, of easy modification to adapt to different ionizable lipid-containing LNPs, and holds great potential for the translation of RNA-based therapeutic strategies.

Impact of enhanced recovery program implementation on postoperative outcomes after liver surgery: a monocentric retrospective study.

INTRODUCTION: It is still unclear whether enhanced recovery programs (ERPs) reduce postoperative morbidity after liver surgery. This study investigated the effect on liver surgery outcomes of labeling as a reference center for ERP. MATERIALS AND METHODS: Perioperative data from 75 consecutive patients who underwent hepatectomy in our institution after implementation and labeling of our ERP were retrospectively compared to 75 patients managed before ERP. Length of hospital stay, postoperative complications, and adherence to protocol were examined. RESULTS: Patient demographics, comorbidities, and intraoperative data were similar in the two groups. Our ERP resulted in shorter length of stay (3 days [1-6] vs. 4 days [2-7.5], p = 0.03) and fewer postoperative complications (24% vs. 45.3%, p = 0.0067). This reduction in postoperative morbidity can be attributed exclusively to a lower rate of minor complications (Clavien-dindo grade < IIIa), and in particular to a lower rate of postoperative ileus, after labeling. (5.3% vs. 25.3%, p = 0.0019). Other medical and surgical complications were not significantly reduced. Adherence to protocol improved after labeling (17 [16-18] vs. 14 [13-16] items, p < 0.001). CONCLUSIONS: The application of a labeled enhanced recovery program for liver surgery was associated with a significant shortening of hospital stay and a halving of postoperative morbidity, mainly ileus.

The Multifunctional Nature of the MicroRNA/AKT3 Regulatory Axis in Human Cancers.

Serine/threonine kinase (AKT) signaling regulates diverse cellular processes and is one of the most important aberrant cell survival mechanisms associated with tumorigenesis, metastasis, and chemoresistance. Targeting AKT has become an effective therapeutic strategy for the treatment of many cancers. AKT3 (PKBγ), the least studied isoform of the AKT family, has emerged as a major contributor to malignancy. AKT3 is frequently overexpressed in human cancers, and many regulatory oncogenic or tumor suppressor small non-coding RNAs (ncRNAs), including microRNAs (miRNAs), have recently been identified to be involved in regulating AKT3 expression. Therefore, a better understanding of regulatory miRNA/AKT3 networks may reveal novel biomarkers for the diagnosis of patients with cancer and may provide invaluable information for developing more effective therapeutic strategies. The aim of this review was to summarize current research progress in the isoform-specific functions of AKT3 in human cancers and the roles of dysregulated miRNA/AKT3 in specific types of human cancers.

Hyaluronan decorated layer-by-layer assembled lipid nanoparticles for miR-181a delivery in glioblastoma treatment.

Glioblastoma multiforme (GBM) is the most common and lethal primary brain cancer. Current pharmacological interventions marginally increase the 12-month overall survival of patients with GBM. Among the novel therapeutic strategies being pursued, micro-RNAs, a class of non-coding RNAs, are receiving considerable attention for their regulation of several pathways implicated in tumorigenesis and survival. Notably, microRNA-181a-5p (miR-181a) has consistently been reported to be downregulated in GBM clinical samples, and its overexpression negatively affects tumor growth both in vitro and in vivo. To improve the delivery of miR-181a to GBM cells, we sought to develop a modified lipid-based nanocarrier capable of encapsulating and delivering miR-181a to GBM cells in vitro and in vivo. Optimized ionizable-lipid containing lipid nanoparticles (LNP) were constructed by covering the miR-181a-loaded LNP with alternating layers of miR-181a, poly-l-arginine and hyaluronic acid through the layer-by-layer technique. The resulting hyaluronan-decorated lipid nanoparticles (HA-LNP) targeted GBM cells more efficiently than non-modified LNP and mediated siRNA and miRNA transfection in vitro. Finally, delivery of miR-181a by HA-LNP induced significant cellular death of U87 GBM cells in vitro and delayed tumor growth in an in vivo subcutaneous tumor model.

MiR-181a-5p inhibits uveal melanoma development by targeting GNAQ and AKT3.

Uveal melanoma (UM) is the most common primary intraocular malignant tumor type in adults. Even after the treatment of the ocular tumor, the prognosis of patients with metastasis remains poor. Hence, an urgent unmet need exists to identify novel approaches to treat advanced UM. Previous studies have revealed G subunit alpha Q and alpha 11 (GNAQ/11) mutations in more than 85% of patients with UM, thus indicating the importance of GNAQ and downstream signaling pathways in UM occurrence. Here, we demonstrate that microRNA (miR)-181a-5p, a small non-coding RNA, effectively inhibited the viability, proliferation, and colony formation but induced apoptosis of UM cells. Furthermore, silencing GNAQ or AKT3 mimicked the anti-UM effects of miR-181a-5p, whereas overexpression of GNAQ or AKT3 rescued the anti-UM effects induced by miR-181a-5p. In addition, miR-181a-5p had a stronger effect in decreasing the viability of GNAQ mutant than GNAQ wild-type cells. Moreover, miR-181a-5p suppressed the total expression and phosphorylation of members of the ERK and PI3K/AKT/mTOR signaling pathways. Importantly, miR-181a-5p potently inhibited the growth of UM xenografts in nude mice. MiR-181a-5p also decreased the expression of Ki67, GNAQ, and AKT3, and induced the expression of cleaved-caspase3 in UM tumors. These results suggest that miR-181a-5p inhibits UM development by targeting GNAQ and AKT3.

Impact of preoperative treatment with antidepressants and/or anxiolytics on outcomes after colorectal surgery with an enhanced recovery programme: a monocentric retrospective study.

BACKGROUND: Preoperative use of antidepressants and anxiolytics was reported to increase length of hospital stay (LOS) and worsen surgical outcomes. However, the surgical procedures studied were seldom performed with an enhanced recovery programme (ERP). This study investigated whether these medications impaired postoperative recovery after colorectal surgery with an ERP. METHODS: The data of all patients scheduled for colorectal surgery between November 2015 and December 2019 prospectively included in our database were analysed. All the patients were managed with the same ERP. Demographic data, risk factors, incidence of postoperative complications, LOS, and adherence to the ERP were compared between patients with and without preoperative antidepressant and/or anxiolytic treatment. RESULTS: Of the 502 patients, 157 (31.3%) were treated with antidepressants and/or anxiolytics. They were older (65.7 vs. 59.5 years, p < 0.001), sicker (higher ASA physical status score, p = 0.001), and underwent surgery more frequently for cancer (73.9 vs. 56.8%, p < 0.001). Overall adherence to ERP (p = 0.99) and adherence to the postoperative items of ERP (p = 0.29), incidence of postoperative complications (35.7 vs. 33.2%, p = 0.61), and LOS (4 [2-7] vs. 4 [2-7], p = 0.99) were similar in the two groups. CONCLUSIONS: Our findings suggest that preoperative treatment with antidepressants and/or anxiolytics does not worsen outcome after elective colorectal surgery with an ERP, does not impact adherence to ERP, and does not prolong LOS. ERP seems efficacious in patients treated with these medications, who should therefore not be excluded from this programme.

The Role of MiR-181 Family Members in Endothelial Cell Dysfunction and Tumor Angiogenesis.

Endothelial dysfunction plays a critical role in many human angiogenesis-related diseases, including cancer and retinopathies. Small non-coding microRNAs (miRNAs) repress gene expression at the post-transcriptional level. They are critical for endothelial cell gene expression and function and are involved in many pathophysiological processes. The miR-181 family is one of the essential angiogenic regulators. This review summarizes the current state of knowledge of the role of miR-181 family members in endothelial cell dysfunction, with emphasis on their pathophysiological roles in aberrant angiogenesis. The actions of miR-181 members are summarized concerning their targets and associated major angiogenic signaling pathways in a cancer-specific context. Elucidating the underlying functional mechanisms of miR-181 family members that are dysregulated in endothelial cells or cancer cells is invaluable for developing miRNA-based therapeutics for angiogenesis-related diseases such as retinopathies, angiogenic tumors, and cancer. Finally, potential clinical applications of miR-181 family members in anti-angiogenic tumor therapy are discussed.

Pain Characteristics in Patients with Inflammatory Bowel Disease: A Monocentric Cross-Sectional Study.

BACKGROUND AND AIMS: The abdominal pain common in inflammatory bowel disease [IBD] patients is traditionally associated with inflammation but may persist during clinical remission. Central sensitization [CS] has not previously been explored in these patients. This study aimed to determine the epidemiology of pain in IBD patients and to specify pain characteristics with particular attention to CS. METHODS: This cross-sectional study included 200 patients; 67% had Crohn's disease [CD]. Pain was assessed using the McGill questionnaire, using the Douleur Neuropathique 4 [DN4] questionnaire and by clinical examination. Its impacts on quality of life, depression and anxiety were also assessed. RESULTS: Three-quarters of IBD patients complained of pain, including intermittent pain attacks, 62% reported abdominal pain and 17.5% had CS. The prevalence of pain [83.6% vs 59.1%; p < 0.001] and abdominal pain [68.7% vs 48.5%; p = 0.006] was higher in CD patients than in ulcerative colitis [UC] patients. Multivariate analysis confirmed that age [p = 0.02], sex [female] [p = 0.004] and CD [p = 0.005] were independent risk factors for pain. Pain intensity was greater in the case of CS (6 [5-3] vs 3 [1.5-5], p < 0.003) which significantly impaired quality of life [p < 0.003] compared with pain without CS. CONCLUSIONS: The prevalence of pain was high in IBD patients [≈75%] and higher in CD patients. Significant impacts on quality of life were confirmed. More than 25% of patients with abdominal pain described CS as responsible for more severe pain and worsened quality of life. TRIAL REGISTRATION REF: NCT04488146.

The impact of orthostatic intolerance on early ambulation following abdominal surgery in an enhanced recovery programme.

BACKGROUND: The prevalence of orthostatic intolerance on the day of surgery is more than 50% after abdominal surgery. The impact of orthostatic intolerance on ambulation on the day of surgery has been little studied. We investigated orthostatic intolerance and walking ability after colorectal and bariatric surgery in an enhanced recovery programme. METHODS: Eighty-two patients (colorectal: n = 46, bariatric n = 36) were included and analysed in this prospective study. Walk tests for 2 min (2-MWT) and 6 min (6-MWT) were performed before and 24 h after surgery, and 3 h after surgery for 2-MWT. Orthostatic intolerance characterised by presyncopal symptoms when rising was recorded at the same time points. Multivariate binary logistic regressions modelling the probability of orthostatic intolerance and walking inability were performed taking into account potential risk factors. RESULTS: Prevalence of orthostatic intolerance and walking inability was, respectively, 65% and 18% 3-hour after surgery. The day after surgery, patients' performance had greatly improved: approximately 20% of the patients experienced orthostatic intolerance, whilst only 5% of the patients were unable to walk. Adjusted binary logistic regressions demonstrated that age (p = .37), sex (p = .39), BMI (p = .74), duration of anaesthesia (p = .71) and type of surgery (p = .71) did not significantly influence walking ability. CONCLUSION: Our study confirms that orthostatic intolerance was frequent (~ 60%) 3-hour after abdominal surgery but prevented a 2-MWT only in ~20% of patients. No risk factors for orthostatic intolerance and walking inability were evidenced.

Potential of miRNA-Based Nanotherapeutics for Uveal Melanoma.

Uveal melanoma (UM) is the most common adult intraocular cancer, and metastatic UM remains deadly and incurable. UM is a complex disease associated with the deregulation of numerous genes and redundant intracellular signaling pathways. As understanding of epigenetic dysregulation in the oncogenesis of UM has increased, the abnormal expression of microRNAs (miRNAs) has been found to be an epigenetic mechanism underlying UM tumorigenesis. A growing number of miRNAs are being found to be associated with aberrant signaling pathways in UM, and some have been investigated and functionally characterized in preclinical settings. This review summarizes the miRNAs with promising therapeutic potential for UM treatment, paying special attention to the therapeutic miRNAs (miRNA mimics or inhibitors) used to restore dysregulated miRNAs to their normal levels. However, several physical and physiological limitations associated with therapeutic miRNAs have prevented their translation to cancer therapeutics. With the advent of nanotechnology delivery systems, the development of effective targeted therapies for patients with UM has received great attention. Therefore, this review provides an overview of the use of nanotechnology drug delivery systems, particularly nanocarriers that can be loaded with therapeutic miRNAs for effective delivery into target cells. The development of miRNA-based therapeutics with nanotechnology-based delivery systems may overcome the barriers of therapeutic miRNAs, thereby enabling their translation to therapeutics, enabling more effective targeting of UM cells and consequently improving therapeutic outcomes.

Histone deacetylase (HDAC) 9: versatile biological functions and emerging roles in human cancer.

BACKGROUND: HDAC9 (histone deacetylase 9) belongs to the class IIa family of histone deacetylases. This enzyme can shuttle freely between the nucleus and cytoplasm and promotes tissue-specific transcriptional regulation by interacting with histone and non-histone substrates. HDAC9 plays an essential role in diverse physiological processes including cardiac muscle development, bone formation, adipocyte differentiation and innate immunity. HDAC9 inhibition or activation is therefore a promising avenue for therapeutic intervention in several diseases. HDAC9 overexpression is also common in cancer cells, where HDAC9 alters the expression and activity of numerous relevant proteins involved in carcinogenesis. CONCLUSIONS: This review summarizes the most recent discoveries regarding HDAC9 as a crucial regulator of specific physiological systems and, more importantly, highlights the diverse spectrum of HDAC9-mediated posttranslational modifications and their contributions to cancer pathogenesis. HDAC9 is a potential novel therapeutic target, and the restoration of aberrant expression patterns observed among HDAC9 target genes and their related signaling pathways may provide opportunities to the design of novel anticancer therapeutic strategies.

Tyrosine-Protein Phosphatase Non-receptor Type 9 (PTPN9) Negatively Regulates the Paracrine Vasoprotective Activity of Bone-Marrow Derived Pro-angiogenic Cells: Impact on Vascular Degeneration in Oxygen-Induced Retinopathy.

BACKGROUND AND AIM: Insufficient post-ischemic neovascularization is an initial key step in the pathogenesis of Oxygen-Induced Retinopathy (OIR). During neovascularization, pro-angiogenic cells (PACs) are mobilized from the bone marrow and integrate into ischemic tissues to promote angiogenesis. However, the modulation of PAC paracrine activity during OIR and the specific mechanisms involved remain to be explored. Because Tyrosine-protein phosphatase non-receptor type 9 (PTPN9) is reported to be a negative regulator of stem cell differentiation and angiogenesis signaling, we investigated its effect on PAC activity in the context of OIR. METHODS AND RESULTS: In a rat model of OIR, higher levels of PTPN9 in the retina and in bone marrow derived PACs are associated with retinal avascular areas, lower levels of the mobilization factor SDF-1 and decreased number of CD34+/CD117+/CD133+ PACs. PACs exposed ex vivo to hyperoxia display increased PTPN9 expression, which is associated with impaired ability of PAC secretome to promote angiogenesis ex vivo (choroidal vascular sprouting) and in vitro (endothelial cell tubule formation) compared to the secretome of PACs maintained in normoxia. Suppression of PTPN9 (using siRNA) increases VEGF and SDF-1 expression to normalize PAC secretome during hyperoxia, leading to restored angiogenic ability of PAC secretome. Moreover, endothelial cells exposed to the secretome of siPTPN9-treated PACs expressed increased levels of activated form of VEGF receptor 2 (VEGFR2). In the rat model of OIR, intravitreal injection of secretome from siPTPN9-treated PACs significantly reduced retinal vaso-obliteration; this was associated with higher retinal levels of VEGF/SDF-1, and increased recruitment of PACs (CD34+ cells) to the retinal and choroidal vessels. CONCLUSION: Our results suggest that hyperoxia alters the paracrine proangiogenic activity of BM-PACs by inducing PTPN9, which can contribute to impair post-ischemic revascularization in the context of OIR. Targeting PTPN9 restores PAC angiogenic properties, and provide a new target for vessel integrity in ischemic retinopathies.

Impact of Preoperative Anemia on Outcomes of Enhanced Recovery Program After Colorectal Surgery: A Monocentric Retrospective Study.

BACKGROUND: Anemia is common before major abdominal surgery (35%). It is an independent factor for postoperative complications and longer length of stay (LOS). The aim of this study was to evaluate the extent to which preoperative anemia impacts on enhanced recovery programs (ERP) outcomes. MATERIALS AND METHODS: The data for patients scheduled for colorectal surgery between 2015 and 2019, were analyzed (n = 494). All patients were managed with the same ERP. Demographic data, preoperative risk factors, postoperative complications, LOS and adherence to ERP were compared between anemic and non-anemic patients. Anemia was defined by a hemoglobin concentration < 13 g dL-1 in men and < 12 g dL-1 in women. RESULTS AND DISCUSSION: In total, 173 patients had preoperative anemia. They were older (p < 0.001) and more often male (p = 0.02). The following risk factors were significantly more frequent in the anemic group: renal failure (p = 0.04), malnutrition (p < 0.001), cardiac arrhythmia (p < 0.001), coronaropathy (p = 0.02) and anticoagulant treatment (p < 0.001). Despite more risk factors, anemic patients did not experience more postoperative complications (38.2% vs. 31.2%, p = 0.12). Overall adherence to ERP was similar (18 [16-19] vs. 18 [17-19], p = 0.06). LOS was 4 [3-7] and 3 [2-6.25] days in the anemic and the non-anemic groups, respectively (p < 0.002). Multivariate analysis showed that anemia did not affect LOS (p = 0.27). CONCLUSION: Our study suggests that preoperative anemia does not detract from the benefits of ERP after elective colorectal surgery.

Anesthetic Management of a Child With Rapid-Onset Dystonia-Parkinsonism (DYT12-ATP1A3): A Case Report.

Rapid-onset dystonia-parkinsonism also known as DYT12-ATP1A3 is an extremely rare neurological disease. Patients develop dystonia, bradykinesia, postural instability, dysarthria, and dysphagia. Injection of botulinum toxin is the first-choice treatment for focal dystonia. We report the case of a 14-year-old patient diagnosed with rapid-onset dystonia-parkinsonism who was scheduled for injection of botulinum toxin in his upper limbs under general anesthesia. To our knowledge, there is no previous report about the anesthetic management of patients with rapid-onset dystonia-parkinsonism.

MicroRNA-181a suppresses norethisterone-promoted tumorigenesis of breast epithelial MCF10A cells through the PGRMC1/EGFR-PI3K/Akt/mTOR signaling pathway.

BACKGROUND: Research suggests that hormone replacement therapy may increase the risk of breast cancer, and progestins such as norethisterone (NET) play a key role in this phenomenon. We have demonstrated that microRNA-181a (miR-181a) suppresses NET-promoted breast cancer cell survival. Nonetheless, the effects of NET and miR-181a on the tumorigenesis of human breast epithelial cells have not yet been elaborated. METHODS: Assays of cell viability, proliferation, migration, apoptosis, and colony formation were performed to investigate the pro-tumorigenesis effect of NET and the effects of miR-181a on human breast epithelial MCF10A cells. The expressions of cell-proliferation-related genes and apoptotic factors were analyzed by quantitative RT-PCR and Western blot in MCF10A cells treated with NET and miR-181a. RESULTS: NET significantly increased MCF10A cell viability, proliferation, migration, and colony formation, but reduced cellular apoptosis. In addition, NET increased the expression of progesterone receptor membrane component 1 (PGRMC1), EGFR, B-cell lymphoma 2, cyclin D1, and proliferating cell nuclear antigen, but decreased the expression of pro-apoptosis factors, such as Bax, caspase-7, and caspase-9. Overexpression of miR-181a strongly inhibited the effects of NET on MCF10A cells and abrogated NET-stimulated PGRMC1, EGFR, and mTOR expression. CONCLUSIONS: Activation of the PGRMC1/EGFR-PI3K/Akt/mTOR signaling pathway is the primary mechanism underlying the pro-tumorigenesis effects of NET on human breast epithelial MCF10A cells. Additionally, miR-181a can suppress the effects of NET on these cells. These data suggest a therapeutic potential for miR-181a in reducing or preventing the risk of breast cancer in hormone replacement therapy using NET.

Comparison of outcome after right colectomy with an enhanced recovery programme in patients with inflammatory bowel disease and patients operated on for other conditions: a monocentric retrospective study.

PURPOSE: Enhanced recovery programmes (ERPs) after surgery reduce postoperative complications and hospital stay. Patients with inflammatory bowel disease (IBD) often present risk factors for postoperative complications. This accounts for reluctance to include them in ERPs. We compared outcome after right colectomy with an ERP in IBD and non-IBD patients. METHODS: In our GRACE colorectal surgery database comprising 508 patients, we analysed patients scheduled for right colectomy (n = 160). Adherence to the protocol, postoperative complications and length of hospital stay of IBD patients (n = 45) were compared with those of non-IBD patients (n = 115). Data (mean ± SD, median [IQR], count (%)) were compared by Student's t, Mann-Whitney U and chi-square tests when appropriate; p < 0.05 taken as statistically significant. RESULTS: IBD patients were significantly younger (38.9 ± 13.8 vs. 58.9 ± 18.5 years, p < 0.001) and had lower BMI (23.0 ± 5.0 vs. 25.1 ± 5.0 kg m-2, p < 0.01). Adherence to ERP was similar in the two groups. Resumption of eating on the day of the operation was less well tolerated (73.3% vs. 85.2%, p < 0.05) and postoperative pain (p < 0.001) was greater in IBD patients. The incidence of postoperative complications (13.3% vs. 17.3%) and the length of hospital stay (3 [3-4.5] vs. 3 [2-5] days) were comparable in IBD and non-IBD patients, respectively. CONCLUSION: The management of IBD patients in an ERP is not only feasible but also indicated. These patients benefit as much from ERP as non-IBD patients.

Lymphocytic microparticles suppress retinal angiogenesis via targeting Müller cells in the ischemic retinopathy mouse model.

Retinopathy of prematurity (ROP) is the primary cause of visual impairment and vision loss in premature infants, which results from the formation of aberrant retinal neovascularization (NV). An emerging body of evidence has shown that Müller cells are the predominant source of vascular endothelial growth factor (VEGF), which also serves as a chemoattractant for monocyte/macrophage lineage. The recruitment of macrophages is increased during retinal NV, and they exert a pro-angiogenic role in ROP. We have shown that lymphocytic microparticles (microvesicles; LMPs) derived from apoptotic human T lymphocytes possess strong angiogenesis-inhibiting properties. Here, we investigated the effect of LMPs on the chemotactic capacity of Müller cells in vitro using rat Müller cell rMC-1 and mouse macrophage RAW 264.7. In addition, the impact of LMPs was determined in vivo using a mouse model of oxygen-induced ischemic retinopathy (OIR). The results revealed that LMPs were internalized by rMC-1 and reduced their cell proliferation dose-dependently without inducing cell apoptosis. LMPs inhibited the chemotactic capacity of rMC-1 on RAW 264.7 via reducing the expression of VEGF. Moreover, LMPs attenuated pathological retinal NV and the infiltration of macrophages in vivo. LMPs downregulated ERK1/2 and HIF-1α both in vitro and in vivo. These findings expand our understanding of the effects of LMPs, providing evidence of LMPs as a promising therapeutic approach for the treatment of retinal NV diseases.