Expression analysis, clinical significance and potential function of PLXNB2 in acute myeloid leukaemia.

BACKGROUND: The overall survival (OS) rate of adult patients suffering from acute myeloid leukaemia (AML) remains unsatisfactory at less than 40%. Current risk stratification systems fail to provide accurate guidelines for precise treatment. Novel biomarkers for predicting prognosis are urgently needed. Plexin B2 (PLXNB2), a functional receptor of angiogenin (ANG), has been found to be aberrantly expressed in multitudinous tumours. We detected overexpression of PLXNB2 mRNA in AML via transcriptome microarray analysis. This study aims to explore the potential role of PLXNB2 as a biomarker of prognosis and a prospective target of AML. METHODS: qRT‒PCR was conducted to verify the expression of PLXNB2 mRNA in bone marrow mononuclear cells from AML patients. Immunohistochemical and immunofluorescence staining were performed and confirmed increased expression of PLXNB2 protein in AML bone marrow tissues. Data on PLXNB2 expression, prognosis and clinical features were accessed from multiple bioinformatic databases, including The Cancer Genome Atlas (TCGA). Genes coexpressed and correlated with PLXNB2 were identified and analysed in the TCGA AML cohort. Metascape was applied for functional and pathway enrichment analysis of genes related to PLXNB2. Small molecular agents and traditional Chinese medicines potentially targeting genes related to PLXNB2 were screened via the Connectivity Map, TCMSP and HIT databases. RESULTS: PLXNB2 mRNA and protein levels are higher in AML samples than in normal controls. Overexpression of PLXNB2 is associated with worse OS in AML. Patients with high PLXNB2 expression might benefit more from haematopoietic stem cell transplantation (HSCT) (indicated by prolonged OS) than those with only chemotherapy treatment. Differentially expressed genes between the high and low PLXNB2 expression groups were overlapped with PLXNB2-coexpressed genes, and genes that overlapped were enriched in immune functions, endothelial cell regulation and cell interaction gene sets, indicating the potential function of PLXNB2 in AML. A total of 36 hub genes were identified from the differentially expressed genes, and MRC1, IL10, CD163 and CCL22 had significant prognostic value for AML. Analysis of the connectivity map and traditional agents revealed that honokiol, morphines, triptolide and paeoniflorin could be potential treatment regimens. CONCLUSIONS: The overexpression of PLXNB2 is an adverse prognostic factor in adult AML patients and could be used as a potential biomarker. PLXNB2 might exert an oncogenic role by modulating immune functions, endothelial cell functions and cell interactions. AML patients with high PLXNB2 expression could benefit more from HSCT.

Efficacy and safety of an HDACi- and HMA-based protocol in adults with acute myeloid leukemia of intermediate- and adverse-risk categories: a retrospective study.

OBJECTIVE: Anthracyclines and cytarabine have comprised standard induction therapy for acute myeloid leukemia (AML) for decades. Low overall survival of AML is due to non-remission or relapse after remission. Hypomethylating agent (HMA) decitabine combined with low-dose chemotherapy or other targeted agents has shown promising effect for AML in clinical trials, especially in t(8;21) acute myeloid leukemia. We previously investigated histone deacetylase inhibitor (HDACi) chidamide could regulate Wnt/ß-catenin signaling pathway in leukemia cell lines. METHODS: Adult patients with de novo or relapsed/refractory AML who were treated with chidamide and decitabine in combination with chemotherapy (chidamide group, n = 23) or only decitabine combination with chemotherapy (decitabine group, n = 17) were analyzed. RESULTS: Chidamide group represented higher complete response rate (82.6% and 52.9%, p = 0.0430, vs. decitabine group), progression-free survival and overall survival rates (p = 0.0088 and p = 0.0139, respectively), especially for patients with de novo AML. Hematological toxicity and infections were the most common adverse events (AEs) in both groups, and they were manageable by supportive treatments. CONCLUSIONS: This HDACi- and HMA-based protocol is an effective and tolerable therapy for patients with AML. The comprehensive mechanism and effects of chidamide in combination with decitabine are worth to be further explored in AML.

Exosomal MiR-4261 mediates calcium overload in RBCs by downregulating the expression of ATP2B4 in multiple myeloma.

Background: Hypercalcemia induced by multiple myeloma (MM) affects the biological functions of excitable and non-excitable cells. However, red blood cells (RBCs) regulatory effect on calcium in hypercalcemia is still not fully understood. Methods: A total of 113 patients with MM osteolytic lesions were studied retrospectively. Flow cytometry and atomic absorption spectroscopy were used to detect calcium content. Immunofluorescence and Western blotting were used to investigate protein expression. GEO and miRNA databases were used to screen miRNAs. Exosomal miR-4261 migration was investigated by Transwell assay. Dual-luciferase assays confirmed the targeting relationship between miR-4261 and ATP2B4. An RBC oxidative stress model was constructed, and Omega-Agatoxin IVA was used to study the role of plasma membrane Ca2+-ATPase 4 (PMCA4) in RBCs. Results: The results showed that MM RBCs had calcium overload, and serum calcium levels increased as the number of RBCs decreased. The expression of PMCA4 in MM RBCs was significantly lower than in normal RBCs. The exosomal miR-4261 produced by MM cells could be transferred to RBCs to downregulate the expression of ATP2B4. Conclusions: Studies have confirmed that RBCs experience calcium overload in MM with osteolytic lesions, which is related to the downregulation of ATP2B4 by MM exosomal miR-4261.

Optic nerve head astrocytes contribute to vascular associated effects.

Purpose: This study was conducted in order to test the expression of vasoactive substances within rat lamina cribrosa (LC) and optic nerve head (ONH) astrocytes, so as to investigate the role and potential mechanism of ONH astrocytes in vascular associated effects. Methods: LC tissue sections and primary cultured ONH astrocytes were obtained from adult Sprague-Dawley (SD) rats. Immunofluorescent staining was then used to detect the expression of vasoactive substances. Hyperoxia exposure was carried out both in vivo and in vitro, after which nitric oxide (NO) levels in LC tissue and cell supernatant were detected. The variations of protein and gene expression associated with vasoactive substances were subsequently tested. ONH astrocytes and vascular smooth muscle cells (VSMCs) were then incubated in a direct co-culture manner. Morphological parameters of VSMCs were finally analyzed in order to evaluate cell contraction. Results: Endothelin-1 (ET-1), nitric oxide synthase (NOS) and renin-angiotensin system (RAS) were detected in both LC tissue and ONH astrocytes. Retinal vessel diameter was found obviously decreased following hyperoxia exposure. Moreover, hyperoxia inhibited NO production both in vivo and in vitro. ET-1 and RAS elements were observed to be upregulated, whereas NOS was downregulated. In ONH astrocytes and VSMCs co-culture system, the length-to-width ratio of VSMCs was shown to significantly increase on days 3 and 7 in hyperoxia compared with normoxia. Conclusions: There is an abundance of expression of vasoactive substances within LC tissue and ONH astrocytes. The contractile response of VSMCs in the co-culture system provided direct evidence for the involvement of ONH astrocytes in vascular associated effects, which may signify a potentially novel direction for future research.

Novel Prognostic Signatures of Hepatocellular Carcinoma Based on Metabolic Pathway Phenotypes.

Hepatocellular carcinoma is a disastrous cancer with an aberrant metabolism. In this study, we aimed to assess the role of metabolism in the prognosis of hepatocellular carcinoma. Ten metabolism-related pathways were identified to classify the hepatocellular carcinoma into two clusters: Metabolism_H and Metabolism_L. Compared with Metabolism_L, patients in Metabolism_H had lower survival rates with more mutated TP53 genes and more immune infiltration. Moreover, risk scores for predicting overall survival based on eleven differentially expressed metabolic genes were developed by the least absolute shrinkage and selection operator (LASSO)-Cox regression model in The Cancer Genome Atlas (TCGA) dataset, which was validated in the International Cancer Genome Consortium (ICGC) dataset. The immunohistochemistry staining of liver cancer patient specimens also identified that the 11 genes were associated with the prognosis of liver cancer patients. Multivariate Cox regression analyses indicated that the differentially expressed metabolic gene-based risk score was also an independent prognostic factor for overall survival. Furthermore, the risk score (AUC = 0.767) outperformed other clinical variables in predicting overall survival. Therefore, the metabolism-related survival-predictor model may predict overall survival excellently for HCC patients.

Development and validation of a ferroptosis-related model for three digestive tract tumors based on a pan-cancer analysis.

Aims: To develop a ferroptosis gene-based survival-predictor model for predicting the prognosis of patients with digestive tract tumors, a pan-caner analysis was performed. Materials & methods: Based on unsupervised clustering and the expression levels of ferroptosis genes, patients with cancer were divided into two clusters. The least absolute shrinkage and selection operator method Cox regression analysis was used to establish the survival-predictor model. Results: Based on the pan-cancer analysis, a 20 gene-based survival-predictor model for predicting survival rates was developed, which was validated in patients with hepatocellular carcinoma. Conclusion: The survival-predictor model accurately predicted the prognosis of patients with digestive tract tumors.

A circular RNA derived from PLXNB2 as a valuable predictor of the prognosis of patients with acute myeloid leukaemia.

BACKGROUND: As a common haematological malignancy, acute myeloid leukaemia (AML), particularly with extramedullary infiltration (EMI), often results in a high mortality rate and poor prognosis. Circular RNAs (circRNAs) regulate biological and pathogenic processes, suggesting a potential role in AML. We have previously described the overall alterations in circRNAs and their regulatory networks between patients with AML presenting with and without EMI. This study aims to find new prognostic and therapeutic targets potentially associated with AML. METHODS: qRT-PCR was performed on samples from 40 patients with AML and 15 healthy controls. The possibility of using circPLXNB2 (circRNA derived from PLXNB2) as a diagnostic and prognostic biomarker for AML was analysed with multiple statistical methods. In vitro, the function of circPLXNB2 was studied by lentivirus transfection, CCK-8 assays, flow cytometry, and Transwell experiments. Western blotting and qRT-PCR were performed to detect the expression of related proteins and genes. The distribution of circPLXNB2 in cells was observed using RNA fluorescence in situ hybridization (RNA-FISH). We also investigated the role of circPLXNB2 by establishing AML xenograft models in NOD/SCID mice. RESULTS: By analysing the results of qRT-PCR detection of clinical samples, the expression of the circPLXNB2 and PLXNB2 mRNAs were significantly increased in patients with AML, more specifically in patients with AML presenting with EMI. High circPLXNB2 expression was associated with an obviously shorter overall survival and leukaemia-free survival of patients with AML. The circPLXNB2 expression was positively correlated with PLXNB2 mRNA expression, as evidenced by Pearson's correlation analysis. RNA-FISH revealed that circPLXNB2 is mainly located in the nucleus. In vitro and in vivo, circPLXNB2 promoted cell proliferation and migration and inhibited apoptosis. Notably, circPLXNB2 also increased the expression of PLXNB2, BCL2 and cyclin D1, and reduced the expression of BAX. CONCLUSION: In summary, we validated the high expression of circPLXNB2 and PLXNB2 in patients with AML. Elevated circPLXNB2 levels were associated with poor clinical outcomes in patients with AML. Importantly, circPLXNB2 accelerated tumour growth and progression, possibly by regulating PLXNB2 expression. Our study highlights the potential of circPLXNB2 as a new prognostic predictor and therapeutic target for AML in the future.

Histone deacetylase inhibitor chidamide regulates the Wnt/ß-catenin pathway by MYCN/DKK3 in B-ALL.

Our previous studies revealed that MYCN downregulates the expression of DKK3, activates the Wnt/ß-catenin signalling pathway at the transcriptional level, and thereby promotes the development of B cell acute lymphocytic leukaemia (B-ALL) but does not affect the methylation of the DKK3 promoter. Some studies have shown that MYCN is associated with histone acetylation. We speculate that histone deacetylase inhibitors (HDACis) can inhibit the Wnt/ß-catenin signalling pathway by inhibiting MYCN and increasing the expression of DKK3. Based on previous experiments, we tested this hypothesis by analysing the changes in MYCN, DKK3 and the Wnt/ß-catenin signalling pathways in B-ALL cells after treatment with the selective HDACi chidamide. The in vitro and in vivo experiments confirmed that chidamide inhibited the expression of MYCN and increased the expression of DKK3 by inhibiting the activity of histone deacetylase, and these effects resulted in inhibition of the Wnt/ß-catenin signalling pathway and the proliferation of B-ALL cells. These findings indicate that chidamide might be used alone or in combination with other chemotherapy regimens for patients with B-ALL and thus provide a new approach to the treatment of B-ALL.

Evaluation of a rabbit model of adjacent intervertebral disc degeneration after fixation and fusion and maintenance in an upright feeding cage.

Purpose: To establish an animal model of adjacent intervertebral disc degeneration by performing spinal fixation and fusion after percutaneous needle puncture and removal of the intervertebral disc or percutaneous needling of the vertebral body without removal of the intervertebral disc. Methods: We established a model of adjacent intervertebral disc degeneration after spinal fixation and fusion of rabbits maintained in upright feeding cages. Twenty-five healthy New Zealand rabbits were used. In the experimental group, the L3-4 intervertebral disc was percutaneously punctured with an 18-G needle under fluoroscopic guidance. Once degeneration occurred, the L3-4 disc was excised, and interbody fusion was performed. The changes in the adjacent intervertebral discs were observed periodically via X-ray and MRI. In the control group, the L3 vertebral body was percutaneously needled with an 18-G needle under fluoroscopic guidance. The changes in the adjacent intervertebral discs were observed on X-ray and MRI at 4, 8, and 12 weeks after puncture in both groups. At 12 weeks postoperatively, the animals were euthanized, and the histopathologic changes of the adjacent intervertebral discs were assessed using hematoxylin-eosin and TdT-mediated dUTP nick end labeling (TUNEL) staining. The mRNA and protein expressions of aggrecanase-1 were measured by real-time quantitative PCR and Western blot analysis. The product of aggrecan degradation, Aggrecan ARGxx, was measured by Western blot analysis. Results: The degeneration of the intervertebral discs in the adjacent segments in the experimental group increased over time. The mRNA and protein expressions of aggrecanase-1 and the expression of Aggrecan ARGxx in the experimental group were significantly increased after puncture, fixation, and fusion (P<0.05). The adjacent intervertebral disc sections had a significantly lower cell density and significantly higher TUNEL-positive cell rate in the experimental group than the control group (P<0.05). Conclusion: The results suggest that the occurrence of intervertebral disc degeneration in adjacent segments may begin with the degeneration of the punctured intervertebral disc.

A Pilot Clinical Study of Intravitreal Injection of Artesunate for Ocular Neovascularization.

Purpose: To evaluate the efficacy and primary safety of treatment with artesunate in reducing ocular neovascularization in humans. Methods: Five patients with corneal, iris, and retinal neovascularization and no light perception were treated with intravitreal injections of artesunate 80 µg. Visual acuity, anterior segment photography, fundus fluorescein angiography, and optical coherence tomography were used to evaluate efficacy, while intraocular pressure (IOP) and lens opacity degree were employed to evaluate safety. The primary endpoint was attenuation of neovascularization as determined at 24 weeks, with the last posttreatment follow-up at 52 weeks. Results: Corneal and iris neovascularization, which were secondary to fundus ischemic diseases and retinal neovascularization in all 5 patients, were attenuated after 1 or 2 injections by the 52-week follow-up. Retinal neovascularization was also attenuated, and papilledema was alleviated. The average IOP fell from 25.5 mmHg to 17.66 mmHg. Conclusions: This pilot study determined that intravitreal artesunate injection is efficacious for reducing corneal, iris, and retinal neovascularization. These results indicate that this drug may be a novel alternative to the currently popular antivascular endothelial growth factor drugs used to suppress ocular neovascularization and improve visual function.

Circular RNA regulatory network reveals cell-cell crosstalk in acute myeloid leukemia extramedullary infiltration.

BACKGROUND: Acute myeloid leukemia can develop as myoblasts infiltrate into organs and tissues anywhere other than the bone marrow, which called extramedullary infiltration (EMI), indicating a poor prognosis. Circular RNAs (circRNAs) are a novel class of non-coding RNAs that feature covalently closed continuous loops, suggesting their potential as micro RNA (miRNA) "sponges" that can participate in biological processes and pathogenesis. However, investigations on circRNAs in EMI were conducted rarely. In this study, the overall alterations of circRNAs and their regulatory network between EMI and non-EMI AML were delineated. METHODS: CircRNA and whole genome microarrays derived from EMI and non-EMI AML bone marrow mononuclear cells were carried out. Functional analysis was performed via Gene Ontology and KEGG test methods. The speculated functional roles of circRNAs were based on mRNAs and predicted miRNAs that played intermediate roles. Integrated bioinformatic analysis was conducted to further characterize the circRNA/miRNA/mRNA regulatory network and identify the functions of distinct circRNAs. The Cancer Genome Atlas (TCGA) data were acquired to evaluate the poor prognosis of distinct target genes of circRNAs. Reverse transcription-quantitative polymerase chain reaction was conducted to identify the expression of has_circRNA_0004520. Connectivity map (CMap) analysis was further performed to predict potential therapeutic agents for EMI. RESULTS: 253 circRNAs and 663 genes were upregulated and 259 circRNAs and 838 genes were downregulated in EMI compared to non-EMI AML samples. GO pathways were enriched in progress including cell adhesion (GO:0030155; GO:0007155), migration (GO:0016477; GO:0030334), signal transduction (GO:0009966; GO:0007165) and cell-cell communication. Overlapping circRNAs envolved in pathways related to regulate cell-cell crosstalk, 17 circRNAs were chosen based on their putative roles. 7 target genes of 17 circRNAs (LRRK1, PLXNB2, OLFML2A, LYPD5, APOL3, ZNF511, and ASB2) indicated a poor prognosis, while overexpression of PAPLN and NRXN3 indicated a better one based on data from TCGA. LY-294002, trichostatin A and SB-202190 were identified as therapeutic candidates for EMI by the CMap analysis. CONCLUSION: Taken together, this study reveals the overall alterations of circRNA and mRNA involved in EMI and suggests potential circRNAs may act as biomarkers and targets for early diagnosis and treatment of EMI.

MYCN is a novel oncogenic target in adult B-ALL that activates the Wnt/ß-catenin pathway by suppressing DKK3.

Dickkopf-3 (DKK3) is frequently down-regulated by promoter hypermethylation and is closely associated with a poor prognosis in many cancers. Our previous studies have shown that miR-708 down-regulates DKK3 at the post-transcriptional level in B-ALL. However, whether transcriptional mechanisms lead to DKK3 silencing remains unclear. Here, we analysed the promoter regions of DKK3 by bioinformatics and found binding sites for MYCN. A dual-luciferase reporter gene assay and ChIP experiments revealed that MYCN negatively regulates DKK3 at the transcriptional level in B-ALL cell lines, and using bisulphite sequencing PCR, we affirmed that MYCN has no effect on the methylation of the DKK3 promoter. MYCN silencing in B-ALL cells resulted in reduced cell proliferation, increased apoptosis and G1 phase arrest. Treatment with MYCN siRNA or 5-aza-2'-deoxycytidine (5-AdC), a demethylating agent, significantly increased the levels of DKK3 mRNA and protein and decreased the protein levels of p-GSK3ß and nuclear ß-catenin, which indicates inhibition of the Wnt/ß-catenin pathway in vitro. MYCN knockdown significantly decreased the tumorigenic capacity of Nalm6 cells, which restored DKK3 levels and inhibited the Wnt/ß-catenin pathway in vivo. Our study provides an increased understanding of adult B-ALL pathogenesis, which may be beneficial to the development of effective prognostic markers or therapeutic targets.

Shifts in renin-angiotensin system components, angiogenesis, and oxidative stress-related protein expression in the lamina cribrosa region of streptozotocin-induced diabetic mice.

PURPOSE: This study aimed to analyse shifts in renin-angiotensin system (RAS) components, angiogenesis, and oxidative stress-related protein expression in the lamina cribrosa (LC) region in streptozotocin (STZ)-induced diabetic mice. METHODS: Six months after diabetes induction, the retinal vessels of male C57BL/6 J mice were observed by colour photography, fundus fluorescein angiography (FFA), and immunofluorescent staining following incubation with CD31. Immunofluorescence for glial fibrillary acidic protein (GFAP), alpha-smooth muscle actin (α-SMA),and NG2 was also performed. Angiotensin-converting enzyme 1 (ACE1), angiotensin II type I receptor (AT1R), renin, hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR2), and haeme oxygenase 1 (HO-1) expression levels were confirmed by immunohistochemical and western blotting analyses. RESULTS: Compared with control mice, diabetic mice had significantly higher blood glucose concentrations (p < 0.001) and significantly lower body weights (p < 0.001). Colour photography and FFA did not reveal any vessel abnormalities in the diabetic mice; however, immunostaining of whole-mount retinas revealed an increased number of retinal vessels. Furthermore, histopathological staining showed significant reduction in the whole retinal thickness. GFAP expression was slightly higher, whereas fewer NG2+ pericytes were observed in diabetic mice than in control mice. ACE1, AT1R, renin, HIF-1α, VEGF, VEGFR2, and HO-1 expression were up-regulated in the LC of the STZ-induced diabetic mice. CONCLUSIONS: Collectively, ACE 1, AT1R, HIF-1α, VEGF, VEGFR2, and HO-1 activation in the LC region in diabetic mice may be involved in diabetes via the RAS and induction of angiogenesis and oxidative stress.

Suppression of miR-708 inhibits the Wnt/ß-catenin signaling pathway by activating DKK3 in adult B-all.

Inactivation of Dickkopf-3 (DKK3) is closely associated with a poor prognosis in various solid tumor and hematologic malignancies. Promoter hypermethylation is one potential cause of DKK3 inactivation. However, whether other mechanisms lead to DKK3 inactivation and the subsequent effects of these inactivations on cell proliferation and the Wnt signaling pathway in adult B acute lymphoblastic leukemia (B-ALL) remain unclear. In the present study, we found that low DKK3 expression levels were associated with high miR-708 expression and promoter hypermethylation in adult B-ALL. miR-708 was confirmed to directly decrease DKK3 expression in Nalm-6 and BALL-1 cells. Additionally, a miR-708 inhibitor decreased cell proliferation mainly through apoptosis and cell cycle arrest at the G1 phase, and these effects were eliminated by DKK3 siRNA treatment. Moreover, the demethylating agent 5-aza-2'-deoxycytidine (5-aza) decreased the methylation state of the DKK3 promoter based on methylation-specific PCR (MSP) and bisulfite genomic sequencing PCR (BSP), although this demethylation effect was not enhanced by the miR-708 inhibitor. The miR-708 inhibitor or 5-aza significantly increased DKK3 expression and decreased p-GSK3ß, cyclin D1 and nuclear and cytoplasmic ß-catenin protein expression, indicating that the Wnt/ß-catenin signaling pathway was inhibited. These effects became more pronounced when the miR-708 inhibitor and 5-aza were used simultaneously. These findings provide greater insights into the mechanisms that increase DKK3 expression and suggest that a miR-708 inhibitor and 5-aza might be useful as targeted therapies for adult B-ALL.

Small Molecular-Sized Artesunate Attenuates Ocular Neovascularization via VEGFR2, PKCα, and PDGFR Targets.

Ocular neovascularization (NV) is the primary cause of blindness in many ocular diseases. Large molecular weight anti- vascular endothelial growth factor (VEGF) protein drugs, such as Avastin and Lucentis, have saved the vision of millions. However, approximately 20-30% of patients respond poorly to anti-VEGF treatment. We found that artesunate (ART), a small molecular derivative of artemisinin, had a significant inhibitory effect on ocular NV by downregulating the expression of VEGFR2, PKCα, and PDGFR. ART significantly inhibited retinal NV in rabbits and macular edema in monkeys with greater anterior chamber penetrability and more durable efficacy than Avastin. Our pilot study showed that intravitreal injection of 80 µg ART significantly inhibited iris and corneal NV in a severe retinal detachment case. Our results suggest that ART might be a potential persistent small-molecule drug to manage ocular NV via multi-targets.

Shifts in retinal vessel diameter and oxygen saturation in Chinese type 2 diabetes mellitus patients.

BACKGROUND: The aim of this study was to analyze the shifts in retinal vessel diameter and oxygen saturation in diabetic patients with and without diabetic retinopathy (DR), as well as to assess the association between diabetes duration and either vessel diameter or oxygen saturation. METHODS: In total, 99 Type 2 DM patients were recruited for the study and were divided into three groups: DM with non-obvious retinopathy (DM, n = 29), non-proliferative diabetic retinopathy (NPDR, n = 40), and proliferative diabetic retinopathy (PDR, n = 30). In addition, 78 age-matched healthy individuals were chosen as the control. The diameter and oxygen saturation of the retinal vessels were analyzed using a noninvasive retinal oximeter, and then compared between the three groups and the normal control. Association analysis was applied to analyze the possible influencing factors, including the diameter and oxygen saturation of retinal vessels, on best corrected visual acuity BCVA, as well as the relationship between diabetes duration and the oximetry values. RESULTS: All of the diabetic patients showed thinner arterioles, wider venules, and a smaller arteriolar-to-venular ratio (AVR) than the healthy individuals. The AVR results from the controls through to the PDR group were 0.81 ± 0.07, 0.78 ± 0.07, 0.76 ± 0.07 and 0.67 ± 0.07, respectively. Both the NPDR and PDR groups showed significantly smaller AVR than the control. All of the diabetic patients exhibited higher retinal vessel oxygen saturation than the healthy individuals. Among all of the oximetry values, AVR exhibited the most significant correlation with best corrected visual acuity (BCVA) (ß = 1.533, P < 0.0001). An increased diabetes duration was associated with decreased arteriolar diameter (slope = -0.082 pixels/year, r (2) = 0.085, P = 0.004) and AVR (slope = -0.009/year, r (2) = 0.349, P < 0.001), and with increased venular diameter (slope = 0.104 pixels/year, r (2) = -0.109, P = 0.001). CONCLUSIONS: In this Chinese population with type 2 DM, the thinner arterioles and wider venules point to microvascular dysfunction in DR. The increased oxygen saturation of the retinal vessels suggests that retinal oxygen metabolism is affected in diabetic retinopathy.

Study of retinal vessel oxygen saturation in ischemic and non-ischemic branch retinal vein occlusion.

AIM: To explore how oxygen saturation in retinal blood vessels is altered in ischemic and non-ischemic branch retinal vein occlusion (BRVO). METHODS: Fifty BRVO eyes were divided into ischemic (n=26) and non-ischemic (n=24) groups, based on fundus fluorescein angiography. Healthy individuals (n=52 and n=48, respectively) were also recruited as controls for the two groups. The mean oxygen saturations of the occluded vessels and central vessels were measured by oximetry in the BRVO and control groups. RESULTS: In the ischemic BRVO group, the occluded arterioles oxygen saturation (SaO2-A, 106.0%±14.3%), instead of the occluded venule oxygen saturation (SaO2-V, 60.8%±9.4%), showed increases when compared with those in the same quadrant vessels (SaO2-A, 86.1%±16.5%) in the contralateral eyes (P<0.05). The oxygen saturations of the central vessels showed similar trends with those of the occluded vessels. In the non-ischemic BRVO group, the occluded and central SaO2-V and SaO2-A showed no significant changes. In both the ischemic and non-ischemic BRVOs, the central SaO2-A was significantly increased when compared to healthy individuals. CONCLUSION: Obvious changes in the occluded and central SaO2-A were found in the ischemic BRVO group, indicating that disorders of oxygen metabolism in the arterioles may participate in the pathogenesis of ischemic BRVO.

Retinal vessel oxygen saturation in a healthy young Chinese population.

PURPOSE: To measure retinal vessel oxygen saturation in a healthy young Chinese population and to determine the effects of multiple factors (gender, age, dioptre, vessel diameter and ocular perfusion pressure - OPP) on retinal oxygen saturation. METHODS: A total of 126 healthy Chinese individuals aged from 19 to 30 were included in this study. A retinal oximeter (Oxymap T1) was used to measure retinal vessel oxygen saturation by retinal imaging at two different wavelengths. The mean retinal vessel oxygen saturation (Sat_O2 ) of arterioles, venules and arteriovenous (AV) difference overall and in four separate quadrants were measured. Intra-ocular pressure, blood pressure, finger pulse oximetry value, vessel diameter and dioptre were also measured. The correlations between OPP and dioptre, OPP and vessel diameter, and dioptre and vessel diameter were analysed. And the effects of multiple factors on the retinal oxygen saturation were analysed. RESULTS: The mean oxygen saturation was 93.2 ± 6.3% in the retinal arterioles, 60.4 ± 5.3% in venules and 32.9 ± 6.4% in AV difference. The temporal quadrants had lower measurements of arteriolar and venular oxygen saturation and AV difference compared with nasal quadrants (p < 0.001). The oxygen saturation of the arterioles, venules and AV difference were unaffected by any unique factor. Arteriolar and venular retinal oxygen saturation correlated negatively with the product of dioptre and OPP. Arteriolar retinal oxygen saturation correlated positively with the product of dioptre and vessel diameter. CONCLUSIONS: This study provided a normal reference of Sat_O2 in healthy young Chinese individuals. It was a reflection of the normal state of retinal oxygen metabolism affected by several factors.

Retinal vessel oxygen saturation and vessel diameter in retinitis pigmentosa at various ages.

PURPOSE: This study was conducted to determine whether oxygen saturation and retinal blood vessel diameter are affected by retinitis pigmentosa (RP) at various ages. METHODS: Relative oxygen saturation was measured in retinal blood vessels in 68 RP patients and 136 normal subjects using the Oxymap T1 retinal oximeter. Subjects were divided into two age groups: Group A (20-40 years) and Group B (> 40 years). One randomly selected eye of each subject was used for statistical analysis. Student's t tests were used to analyze the mean saturation and diameter of retinal arterioles and venules and arteriovenous differences between RP and normal subjects in the two age groups. A Spearman test was used to analyze the correlation of mean saturation of retinal arterioles (AS) and arteriovenous differences (AVS) with visual acuity, disease duration, and electroretinogram (ERG) b-wave amplitude in patients with RP. RESULTS: AS was significantly higher in patients with RP (105.5 ± 9.4 %) than in normal subjects (94.5 ± 4.4 %, p = 0.000) in Group A, while in Group B, AS was significantly lower in RP patients (86.8 ± 10.3 %) than in healthy subjects (96.0 ± 4.8 %, p = 0.000). Vessel diameter was smaller in RP patients than in normal subjects. AS and AVS showed a negative correlation with disease duration and a tendency toward positive correlation with ERG b-wave in patients with RP. CONCLUSIONS: The shifting characteristics of retinal vessel oxygen saturation suggest that the pathological mechanism of retinal oxygen metabolic disorder differs by age in patients with RP.

Retinal vessel oxygen saturation and vessel diameter in high myopia.

PURPOSE: To investigate changes in retinal vessel oxygen saturation and diameter in high myopia. METHODS: Relative oxygen saturation was measured in the retinal blood vessels of 54 participants with high myopia and compared to a control group of 54 individuals with emmetropia with the Oxymap T1 retinal oximeter. The participants with high myopia were further divided into two groups according to the grade of myopic retinopathy: Group A (grade < M2 ) and Group B (grade ≥ M2 ). One-way anova was used to analyse the mean saturation and diameter of retinal arterioles and venules and the mean difference in arterio-venous saturation among the four groups. Further analysis of multiple comparisons was performed with the Bonferroni test. Linear regression was used to analyse the correlation of ocular perfusion pressure or best corrected visual acuity with other variables. RESULTS: For all of the high myopia patients, retinal arteriole saturation (92.3 ± 5.6%) and the difference in arterio-venous saturation (30.8 ± 5.0%) were significantly lower than in normal individuals (96.0 ± 5.8%, 35.4 ± 6.2%; p = 0.006, p < 0.001, respectively). In Group A, only the difference in arterio-venous saturation (31.0 ± 4.7%) was significantly lower than in the control group (p = 0.011). In Group B, retinal arteriole saturation (92.2 ± 5.3%) and the difference in arterio-venous saturation (30.7 ± 5.3%) were also lower than the control group (p = 0.02, p = 0.001, respectively). Both retinal arteriole diameter and retinal venule diameter were narrower than in participants with high myopia than the control group (p < 0.001). No statistically significant correlations were found between ocular perfusion pressure or best corrected visual acuity with any other variables. CONCLUSIONS: The study demonstrated decreased retinal arteriole saturation and decreased difference in arterio-venous saturation as well as narrowing retinal vessel diameter in highly myopic eyes. Further studies are needed to determine if such changes play a role in the development of high myopia and its complications or occur as a consequence of tissue remodelling during axial elongation.