Neovascularization In Diabetic Retinopathy Research Articles

LncRNA XIST promotes neovascularization in diabetic retinopathy by regulating miR-101-3p/VEGFA.

This study sought to investigate the regulation of long noncoding RNA (lncRNA) XIST on the microRNA (miR)-101-3p/vascular endothelial growth factor A (VEGFA) axis in neovascularization in diabetic retinopathy (DR). Serum of patients with DR was extracted for the analysis of XIST, miR-101-3p, and VEGFA expression levels. High glucose (HG)-insulted HRMECs and DR model rats were treated with lentiviral vectors. MTT, transwell, and tube formation assays were performed to evaluate cell viability, migration, and angiogenesis, and ELISA was conducted to detect the levels of inflammatory cytokines. Dual-luciferase reporter, RIP, and RNA pull-down experiments were used to validate the relationships among XIST, miR-101-3p, and VEGFA. XIST and VEGFA were upregulated and miR-101-3p was downregulated in serum from patients with DR. XIST knockdown inhibited proliferation, migration, vessel tube formation, and inflammatory responsein HG-treated HRMECs, whereas the above effects were nullified by miR-101-3p inhibition or VEGFA overexpression. miR-101-3p could bind to XIST and VEGFA. XIST promoted DR development in rats by regulating the miR-101-3p/VEGFA axis. LncRNA XIST promotes VEGFA expression by downregulating miR-101-3p, thereby stimulating angiogenesis and inflammatory response in DR.

A deep learning system for the detection of optic disc neovascularization in diabetic retinopathy using optical coherence tomography angiography images

A deep learning system for the detection of optic disc neovascularization in diabetic retinopathy using optical coherence tomography angiography images

Acceleration of moyamoya disease after anti-vascular endothelial growth factor intravitreal injections

Abstract: Moyamoya disease (MMD) is a rare, progressive, irreversible vaso-occlusive disease affecting the cerebral vasculature. The progressive occlusion of blood vessels leads to the development of collateral vessels to compensate for the insufficient blood supply. Some growth factors such as vascular endothelial growth factor (VEGF) may cause excessive and aberrant angiogenesis in MMD. We report a case of a 55-year-old male, following up in retina clinics for diabetic retinopathy and macular edema who received anti-VEGF agents then he presented to the emergency room with left-sided face and body weakness, dysphagia, and dysarthria. Based on his clinical presentation and neuroimaging, he was diagnosed with moyamoya progression. We hypothesize that receiving anti-VEGF agents could have contributed to MMD progression in our patient and interfered with the collateral vessel development in a similar manner to their intended use in regressing neovascularization in diabetic retinopathy.

Therapeutic effect of ultra-long-lasting human C-peptide delivery against hyperglycemia-induced neovascularization in diabetic retinopathy.

Rationale: Neovascularization is a hallmark of the late stages of diabetic retinopathy (DR) leading to blindness. The current anti-DR drugs have clinical disadvantages including short circulation half-lives and the need for frequent intraocular administration. New therapies with long-lasting drug release and minimal side effects are therefore needed. We explored a novel function and mechanism of a proinsulin C-peptide molecule with ultra-long-lasting delivery characteristics for the prevention of retinal neovascularization in proliferative diabetic retinopathy (PDR). Methods: We developed a strategy for ultra-long intraocular delivery of human C-peptide using an intravitreal depot of K9-C-peptide, a human C-peptide conjugated to a thermosensitive biopolymer, and investigated its inhibitory effect on hyperglycemia-induced retinal neovascularization using human retinal endothelial cells (HRECs) and PDR mice. Results: In HRECs, high glucose conditions induced oxidative stress and microvascular permeability, and K9-C-peptide suppressed those effects similarly to unconjugated human C-peptide. A single intravitreal injection of K9-C-peptide in mice resulted in the slow release of human C-peptide that maintained physiological levels of C-peptide in the intraocular space for at least 56 days without inducing retinal cytotoxicity. In PDR mice, intraocular K9-C-peptide attenuated diabetic retinal neovascularization by normalizing hyperglycemia-induced oxidative stress, vascular leakage, and inflammation and restoring blood-retinal barrier function and the balance between pro- and anti-angiogenic factors. Conclusions: K9-C-peptide provides ultra-long-lasting intraocular delivery of human C-peptide as an anti-angiogenic agent to attenuate retinal neovascularization in PDR.

Therapeutic effect of intravitreal anti-VEGF drugs on retinal neovascularization in diabetic retinopathy.

Therapeutic effect of intravitreal anti-VEGF drugs on retinal neovascularization in diabetic retinopathy.

Dickkopf-1 exerts protective effects by inhibiting PANoptosis and retinal neovascularization in diabetic retinopathy

Diabetic retinopathy (DR) is a key reason for legal blindness worldwide. Currently, it is urgently necessary to determine the etiology and pathological molecular mechanism of DR to search for resultful therapies. Dickkopf-1 (DKK1) is inhibitive for canonical Wnt signaling via negative feedback, and has been reported as a biomarker for DR. However, the related mechanisms are still unclear. In this work, our data showed that DKK1 was decreased in the vitreous tissues at an early stage of diabetes triggered by streptozotocin (STZ) injection in rats. We subsequently found that DKK1 intravitreal injection significantly ameliorated the physiological function of retina in STZ-challenged rats, accompanied by improved retinal structure. Surprisingly, our results indicated that DKK1 injection remarkably suppressed PANoptosis in retinal tissues of STZ-challenged rats with DR, as proved by ameliorated pyroptosis, apoptosis and necroptosis, which were mainly through the blockage of cleaved Gasdermin-D (GSDMD), Caspase-3 and receptor-interacting protein kinase-3 (RIPK3). Additionally, Wnt signaling including the expression of Wnt, β-catenin and LDL receptor-related protein 5/6 (LRP5/6) was also highly prohibited in retina of DKK1-injected rats with DR. Furthermore, retinal neovascularization and acellular vessel in DR rats were also considerably abolished after DKK1 injection, accompanied by reduced expression levels of retinal vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-9 (MMP9). More in vitro experiments showed that DKK1 treatment markedly repressed the proliferative and migratory ability of endothelial cells via inhibiting angiogenesis-related molecules. Together, all our results broaden the knowledge of the correlation between DKK1 and DR, and then provide a novel therapeutic strategy for the suppression of management of DR.

Inhibitory effect of maspinon neovascularization in diabetic retinopathy.

BACKGROUNDDiabetic retinopathy (DR) is a serious and potentially blinding complication of diabetes mellitus. Retinal neovascularization is one of the main pathological features of proliferative DR, and inhibiting retinal neovascularization is a research focus.AIMThe aim was to evaluate the effect of intravitreal injection of recombinant human maspin on neovascularization in DR.METHODSAn oxygen-induced retinopathy (OIR) mouse model was used to simulate neovascularization in DR. New born C57BL/6J mice were randomly divided to a normal control group, a maspin injection OIR group, and an OIR group. The mice in the maspin injection OIR group were injected with recombinant human maspin in the bilateral vitreous cavity on postnatal day P12, and those in the OIR group were injected with sterile phosphate buffered saline. The protein expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1-alpha (HIF-1α) in the retina was measured by western blotting, and the mRNA expression of VEGF and HIF-1α was measured by real-time polymerase chain reaction. The vascular cell nuclei that broke through the inner limiting membrane (ILM) were counted in haematoxylin-eosin stained retinal sections.RESULTSIt was found that the number of vascular cell nuclei breaking through the ILM was 31.8 ± 8.75 in the OIR group, which was significantly more than that in the normal control group (P < 0.001). The number of vascular cell nuclei breaking through the ILM was 6.19 ± 2.91 in the maspin injection OIR group, which was significantly less than that in OIR group (P < 0.01). The relative protein and mRNA expression of VEGF and HIF-1α was significantly lower in the retinas in the maspin injection OIR group than in those in the OIR group (P < 0.01).CONCLUSIONMaspin inhibited neovascularization in DR by modulating the HIF-1α/VEGF pathway, which provides a potential and effective strategy for the treatment of DR.

Long non-coding RNA MEG3 inhibits neovascularization in diabetic retinopathy by regulating microRNA miR-6720-5p and cytochrome B5 reductase 2

ABSTRACT Diabetic retinopathy (DR) is a major cause of vision loss in working and elderly populations. long non-coding RNA (LncRNA) MEG3 is thought to have some effect on DR, but the exact mechanism remains to be clarified. The expression levels of lncRNA MEG3, miR-6720-5p, and cytochrome B5 reductase 2 (CYB5R2) in human retinal microvascular endothelial cells (hRMECs) were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), transwell migration, and tube formation assays were used to determine the cell viability, migration, and tube formation ability of hRMECs, respectively. The interaction of MEG3, miR-6720-5p, and CYB5R2 was detected and explored by a luciferase assay. The expression of MEG3 and CYB5R2 was upregulated and that of miR-6720-5p was downregulated in patients with DR and hRMECs treated with high glucose. Knocking down MEG3 or CYB5R2 promoted proliferation, migration, and neovascularization in hRMECs. The intervention of miR-6720-5p reversed the effect of MEG3 knockdown on hRMEC function, and this effect was eliminated by silencing CYB5R2. Therefore, MEG3 acted as a sponge to suppress miR-6720-5p and regulate the expression of CYB5R2, thereby inhibiting DR neovascularization.

MiR-423-5p activated by E2F1 promotes neovascularization in diabetic retinopathy by targeting HIPK2

BackgroundDiabetic retinopathy (DR) is a diabetic complication and the primary cause of blindness in the world. However, the treatments of DR are challenging given its complicated pathogenesis. Here, we investigated the molecular mechanisms of DR by focusing on the function of E2F1/miR-423-5p/HIPK2/HIF1α/VEGF axis.MethodsCultured retinal endothelial cells (hRMECs, hRECs) were treated with 25 mM glucose to mimic the high glucose-induced DR in vitro. Streptozotocin (STZ) was injected into mice to induce DR in mice. qRT-PCR, western blotting, immunohistochemistry, and ELISA were employed to measure levels of E2F1, miR-423-5p, HIPK2, HIF1α, and VEGF. H&E staining was utilized to examine retinal neovascularization. CCK-8 assay, transwell assay, and vascular tube formation assay were used to assess the cell viability, migration, and angiogenesis. Dual luciferase assay was performed to validate interactions between E2F1 and miR-423-5p, miR-423-5p and HIPK2.ResultsHG treatment increased the cell viability, migration, and angiogenesis accompanied by upregulation of E2F1, miR-423-5p, HIF1α, and VEGF levels, but reduction in HIPK2 expression. Knockdown of E2F1 or miR-423-5p suppressed the HG-induced increases in cell viability, migration, and angiogenesis. E2F1 transcriptionally activated miR-423-5p expression and miR-423-5p mimics blocked the effects of E2F1 knockdown on angiogenesis. Moreover, miR-423-5p directly targeted HIPK2 to disinhibit HIF1α/VEGF signaling. Knockdown of HIPK2 reversed the effects of miR-423-5p inhibitor on cell viability, migration, and angiogenesis. Knockdown of E2F1 suppressed neovascularization during DR in vivo.ConclusionsE2F1 activates miR-423-5p transcription during DR to promote angiogenesis via suppressing HIPK2 expression to disinhibit HIF1α/VEGF signaling. Strategies targeting E2F1/miR-423-5p/HIPK2 axis could be potentially used for DR treatment.

Role of Optical Coherence Tomography Angiography to differentiate Intraretinal microvascular abnormalities and retinal neovascularization in Diabetic Retinopathy.

ABSTRACTObjective:To assess proliferative diabetic retinopathy (PDR) and to describe the difference in angiographic representation of new vessels (NVs) and Intra retinal microvascular abnormalities (IRMA) on optical coherence tomography angiography (OCTA).Methods:A cross-sectional observational study was performed at ISRA Postgraduate Institute of Ophthalmology, Karachi, from March 2018 to September 2018. Forty-two eyes of 21 patients with history of diabetes mellitus (DM) were examined. Twenty-eight eyes with a clinical diagnosis of severe non proliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR) according to early treatment diabetic retinopathy study (ETDRS) were included and evaluated using Swept source optical coherence tomography angiography (SS-OCTA). Then face wide field SS-OCTA images and co registered structural optical coherence tomography (OCT) with flow overlay were used to distinguish the features of IRMA and retinal NVs.Results:Forty-two eyes (21 patients) were examined clinically. Fourteen eyes had moderate NPDR, 15 had severe NPDR and 13 eyes had changes consistent with PDR. After clinical diagnosis, we included 28 eyes in our study based on inclusion criteria. These 28 eyes went through SS-OCTA evaluation and we observed 15 cases with PDR and 13 with severe NPDR changes. The OCTA and clinical diagnosis were similar except in 2 eyes, which is critical but not statically significant showing the importance of this noninvasive technology.Conclusions:Widefield OCTA can work as an alternative to fundus fluorescein angiography (FFA) in the diagnosis of diabetic retinopathy (DR). As it is a non-invasive and depth encoded technique so can be used frequently to monitor the retinal changes and their progression.

Sensitivity and specificity of pseudocolor ultrawide field imaging in comparison to wide field fundus fluorescein angiography in detecting retinal neovascularization in diabetic retinopathy.

To evaluate the diagnostic accuracy of ultrawide pseudocolor retinal photography (pseudocolor UWF) compared to wide field fundus fluorescein angiography (WFFFA) in the detection of retinal neovascularization (NV) and NV of the disc (NVD) in patients with diabetic retinopathy (DR). Diagnostic accuracy observational study evaluating pseudocolor UWF as the index test. The reference standard was WFFFA. Single retinal centre in India. People with severe non-proliferative DR (sNPDR), early proliferative DR (ePDR) or high-risk proliferative DR (HR PDR). Sensitivity and specificity of pseudocolor UWF in the detection of NV. A total of 176 eyes of 94 subjects with sNPDR, ePDR or HR PDR underwent pseudocolor UWF and WFFFA. The sensitivity and specificity of pseudocolor UWF in detecting NVE were 92.5% (95% CI 86.2-96.5) and 81% (95% CI 64.8-92.0), respectively, with moderate interobserver agreement of 0.722 (p value 0.001). The positive predictive value and negative predictive value were 83.0 (71.4-90.5) and 91.5 (84.9-95.3), respectively. Compared to WFFFA as the gold standard, pseudocolor UWF has high sensitivity and specificity in detection of NV in all retinal quadrants and NVD. Therefore, pseudocolor UWF may be used as a non-invasive tool for screening and managing DR.

Role of inflammatory regulators in neovascularization of diabetic retinopathy

Role of inflammatory regulators in neovascularization of diabetic retinopathy

Analysis of Progressive Neovascularization in Diabetic Retinopathy Using Widefield OCT Angiography

To document enlarged neovascularization elsewhere (NVE) quantitatively and morphologically using widefield swept-source (SS) OCT angiography (OCTA) with vitreoretinal interface (VRI) slab images. Retrospective, observational imaging study. The study included 46 NVE examples in 25 eyes of 21 consecutive patients who demonstrated severe proliferative diabetic retinopathy with NVE between March 2018 and June 2020 at Osaka University Hospital. All patients underwent ophthalmologic examination, including ultra-widefield fluorescein angiography and widefield SS OCTA scans. We evaluated the area and the vascular density (VD) of NVE lesions detected on five 12× 12-mm2 or two 15× 9-mm2 SS OCTA panoramic VRI slab images obtained at the first and final visits. At baseline, the mean NVE area on OCTA was 1.85 ± 2.81 mm2, and the VD of the NVE lesions was 73.9 ± 14.6%. At the final visit, the mean NVE area on OCTA was 2.14 ± 3.14 mm2, and the mean VD of the NVE lesions was 65.3 ± 17.1%. The average NVE size change (square millimeters per month) was associated significantly with the ischemic index (P= 0.009). Growth of NVE area was classified into 2 patterns: round (61.8%) and ramified (38.2%). The round group tended to have a larger ischemic index at baseline than the ramified group (P= 0.0375). We quantified the size and density of NVE lesions over time. The NVE size increase was associated significantly with the severity of ischemic changes. Furthermore, the round growth pattern was correlated significantly with the ischemic index. These findings suggest that the morphologic features of NVE are associated with more severe ischemia.

Utilisation of optical coherence tomography and optical coherence tomography angiography to assess retinal neovascularisation in diabetic retinopathy.

To evaluate the use of optical coherence tomography angiography (OCTA), structural OCT and fundus fluorescein angiography (FFA) to distinguish neovascularisation elsewhere (NVE) from intra retinal microvascular abnormalities (IRMA) and their use in early detection and possible risk assessment for vitreous haemorrhage. A cross-sectional study of a consecutive series of patients with suspected NVE and IRMA using clinical examination and FFA, were examined further with OCT and OCTA. Treated and untreated eyes were also compared. Images from 33 eyes of 26 patients, showed 27 NVE and 14 IRMA lesions based on clinical examination +/- FFA. Lesions were re-classified as NVE in 22 eyes. Ten eyes had received past treatment. In all 10 treated eyes, vascular flow and vitreous connection were found but not FFA leakage. In 18/22 eyes with NVE there was a breach of the internal limiting membrane (ILM), in 4 eyes there was FFA leak, ILM outpouching but no breach. In two eyes, NVE originated from sea fan IRMA. Ten eyes images were classified as IRMA only with no FFA leak, or ILM breach. The relation of pre-retinal NVE to the vitreous can be visualised. Lesions, considered to be NVE, after further assessment with OCT and OCTA, can be intra-retinal, with ILM disruption but no ILM breach and leakage on FFA. ILM disruption maybe one of the earliest signs of the development of neovascularisation. Visualisation of the relation to the posterior vitreous is likely to be useful in assessing risk of vitreous haemorrhage.

Bone Morphogenetic Proteins and Diabetic Retinopathy.

Bone morphogenetic proteins (BMPs) play an important role in bone formation and repair. Recent studies underscored their essential role in the normal development of several organs and vascular homeostasis in health and diseases. Elevated levels of BMPs have been linked to the development of cardiovascular complications of diabetes mellitus. However, their particular role in the pathogenesis of microvascular dysfunction associated with diabetic retinopathy (DR) is still under-investigated. Accumulated evidence from our and others’ studies suggests the involvement of BMP signaling in retinal inflammation, hyperpermeability and pathological neovascularization in DR and age-related macular degeneration (AMD). Therefore, targeting BMP signaling in diabetes is proposed as a potential therapeutic strategy to halt the development of microvascular dysfunction in retinal diseases, particularly in DR. The goal of this review article is to discuss the biological functions of BMPs, their underlying mechanisms and their potential role in the pathogenesis of DR in particular.

MiR-139-5p promotes neovascularization in diabetic retinopathy by regulating the phosphatase and tensin homolog.

Pathological retinal neovascularization is a driver of the progression of diabetic retinopathy (DR). The present study sought to identify the microRNAs (miRNAs) that are differentially expressed during the progression of DR as well as to explore the specific regulatory mechanism of those miRNAs in retinal neovascularization. Using a microarray data set and a diabetic mouse model, it was determined that miR-139-5p was significantly upregulated during the progression of DR. The in vitro investigation revealed an elevation in the miR-139-5p level in both the high glucose (HG)-treated mouse retinal microvascular endothelial cells (mRMECs) and the HG-treated human RMECs (hRMECs). The miR-139-5p overexpression elevated cell migration, facilitated tube formation, and increased vascular endothelial growth factor (VEGF) protein level in the hRMECs. While the angiogenic effect of miR-139-5p overexpression was halted by an anti-VEGF antibody. Meanwhile, the miR-139-5p knockdown eliminated the VEGF-induced cell migration and tube formation in the hRMECs. The phosphatase and tensin homolog (PTEN) was the target gene of the miR-139-5p. PTEN overexpression removed the angiogenic effect of miR-139-5p overexpression, which led to reduced cell migration and tube formation. In the diabetic mice, the miR-139-5p antagomir effectively decreased the acellular capillaries and suppressed the formation of aberrant blood vessels in the retinal tissues. Taken together, miR-139-5p promotes retinal neovascularization by repressing PTEN expression.

Monounsaturated oleic acid modulates autophagy flux and upregulates angiogenic factor production in human retinal pigment epithelial ARPE-19 cells

AimsDyslipidemia-associated diabetic retinopathy is featured by macular edema and retinal angiogenesis. This study investigated the in vitro lipotoxicity of free fatty acids and their modulatory roles in regulation of autophagy and angiogenic factor production in cultured human retinal pigment epithelium (RPE) ARPE-19 cells. Main methodsARPE-19 cells were exposed to monounsaturated oleic acid (OA), saturated palmitic acid (PA), or both. Cell viability, cell cycle distribution, migration, and autophagy of the treated cells were monitored. Angiogenic factor production was determined by RT-qPCR and ELISA. Key findingsOA, but not PA, at doses higher than 500 μM significantly induced cytostasis and lipotoxicity in ARPE-19 cells. OA exposure not only markedly enhanced autophagy flux, but also enhanced cell migration, while PA suppressed motility of RPE cells. Meanwhile, OA stimulated de novo synthesis of angiogenic factors including VEGF and bFGF in ARPE-19 cells. Mechanistically, OA treatment stimulated not only AMPK/mTOR/p70S6K signaling, but also induced hyperphosphorylation of MAPK pathway mediators, including ERK, JNK and p38 MAPK, as well as NF-κB activation. Kinase inhibition assays showed that blockade of PI3K/Akt, MAPK and NF-κB pathways prevented the OA-upregulated VEGF transcription and its peptide release. Comparatively, only NF-κB inhibition significantly suppressed bFGF peptide release from ARPE-19 cells. SignificanceOut findings support the OA-exhibited cytostasis, autophagy modulation and angiogenic factor production in RPE cells. This study sheds light on the interrelationship between metabolic disorder and retinopathy and provides molecular strategies for preventing and treating choroidal neovascularization in diabetic retinopathy.

MicroRNA-409-5p promotes retinal neovascularization in diabetic retinopathy

ABSTRACT Background: Retinal neovascularization, which is characterized by the increased proliferation, migration, and tube formation of retinal microvascular endothelial cells (RMECs), contributes to the progression of diabetic retinopathy (DR). MiR-409-5p has been reported to be upregulated in peripheral blood of DR patients and in vascular endothelial growth factor (VEGF)-induced RMECs. However, the role of miR-409-5p in retinal neovascularization of DR remains unelucidated. Method: The expression of miR-409-5p was measured in retinal tissues of streptozocin-induced and db/db diabetic mice, in high glucose-induced mouse RMECs (mRMECs), and in vitreous fluid of proliferative DR patients. Antagomir of miR-409-5p was intravitreally injected into diabetic mice. Proliferation, migration, and tube formation were detected using cell counting kit-8 assay, transwell assay, and microscope observation, respectively. Luciferase reporter assay was used to detect the direct interaction between miR-409-5p and peroxisome proliferator-activated receptor-α (PPARα). Result: MiR-409-5p was upregulated in retinal tissues of diabetic mice, in high glucose-induced mRMECs, and in vitreous fluid of proliferative DR patients. The knockdown of miR-409-5p attenuated retinal neovascularization in vivo. The overexpression of miR-409-5p promotes the proliferation, migration, and tube formation, and increased VEGF expression and secretion, while the knockdown of miR-409-5p suppressed the VEGF-induced retinal neovascularization in vitro. PPARα is a downstream target of miR-409-5p, and PPARα overexpression negated the promotion of miR-409-5p overexpression on the proliferation, migration, and tube formation of mRMECs. Conclusion: Our findings demonstrated that miR-409-5p acted as a neovasculogenic factor in DR, and anti-miR-409-5p therapy may provide a novel strategy in treating DR.

Clinical and angiographic characterization of choroidal neovascularization in diabetic retinopathy.

To report the clinical and angiographic characteristics of choroidal neovascularization in patients with diabetic retinopathy. Patients of type 2 diabetes mellitus with presence of choroidal neovascularization in at least one eye were retrospectively analyzed. The study eyes were divided into three groups based on presence (active or scarred) or absence of choroidal neovascularization (fellow eyes). Imaging characteristics of active choroidal neovascularization were recorded using optical coherence tomography, fluorescein, and indocyanine angiography. Central macular thickness, subfoveal choroidal thickness, and large choroidal vessel layer thickness were compared at baseline and final visit. Our study reports the prevalence rate of choroidal neovascularization in eyes with diabetic retinopathy (0.27%; 36 out of 13,382 eyes). A total of 64 eyes of 32 patients (age, mean ± standard deviation: 68.5 ± 9.3 years) with baseline visual acuity of 0.69 ± 0.69 logarithm of minimum angle of resolution (Snellen equivalent 20/100) were included. Nonproliferative diabetic retinopathy (57 eyes) comprised the majority followed by proliferative diabetic retinopathy (7 eyes). Eyes with choroidal neovascularization (36, 56.25%) included both active (25) and scarred (11) choroidal neovascularization, with bilateral choroidal neovascularization in 4 patients. Type 1 choroidal neovascularization was the most common subtype of choroidal neovascularization on optical coherence tomography. Common etiologies for active choroidal neovascularization included age-related macular degeneration (3; 12%), myopia (1; 4%), and inflammatory choroidal neovascularization secondary to chorioretinitis (1; 4%). In the remaining 20 eyes, choroidal neovascularization formation was primarily due to diabetic choroidopathy. The prevalence of choroidal neovascularization in eyes with diabetic retinopathy is very low, with a lower prevalence of age-related macular degeneration. Diabetic choroidopathy plays a significant role in formation of choroidal neovascularization in eyes with diabetic retinopathy.

Expression profiles of long noncoding RNAs in retinopathy of prematurity.

Long noncoding RNA (lncRNA) regulates the proliferation and migration of human retinal endothelial cells, as well as retinal neovascularization in diabetic retinopathy. Based on similarities between the pathogenesis of retinopathy of prematurity (ROP) and diabetic retinopathy, lncRNA may also play a role in ROP. Seven-day-old mice were administered 75 ± 2% oxygen for 5 days and normoxic air for another 5 days to establish a ROP model. Expression of lncRNA and mRNA in the retinal tissue of mice was detected by high-throughput sequencing technology, and biological functions of the resulted differentially expressed RNAs were evaluated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. The results showed that compared with the control group, 57 lncRNAs were differentially expressed, including 43 upregulated and 14 downregulated, in the retinal tissue of ROP mice. Compared with control mice, 42 mRNAs were differentially expressed in the retinal tissue of ROP mice, including 24 upregulated and 18 downregulated mRNAs. Differentially expressed genes were involved in ocular development and related metabolic pathways. The differentially expressed lncRNAs may regulate ROP in mice via microRNAs and multiple signaling pathways. Our results revealed that these differentially expressed lncRNAs may be therapeutic targets for ROP treatment. This study was approved by the Medical Ethics Committee of Shengjing Hospital of China Medical University on February 25, 2016 (approval No. 2016PS074K).