Retinal and Circulating miRNAs in Age-Related Macular Degeneration: An In vivo Animal and Human Study

Romano, Giovanni Luca; Platania, Chiara Bianca Maria; Drago, Filippo; Salomone, Salvatore; Ragusa, Marco; Barbagallo, Cristina; Pietro, Cinzia Di; Purrello, Francesco; Reibaldi, Michele; Avitabile, Teresio; Longo, Antonio; Bucolo, Claudio

doi:10.3389/fphar.2017.00168

Cited by 88 publications

(112 citation statements)

References 68 publications

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“…The other miRNAs analysed (miR‐27a‐5p, miR‐27b‐3p, miR‐206‐3p, and miR‐381‐3p) were up‐regulated both in retina and in serum of diabetic mice. These data, particularly miR‐27a up‐regulation, are in accordance with previous studies on patients affected by AMD and choroidal neovascularization (Ren et al, ; Romano et al, ). Furthermore, retinal miR‐27a was up‐regulated in an animal model of AMD (Romano et al, ).…”

Section: Discussionsupporting

confidence: 92%

“…These data, particularly miR‐27a up‐regulation, are in accordance with previous studies on patients affected by AMD and choroidal neovascularization (Ren et al, ; Romano et al, ). Furthermore, retinal miR‐27a was up‐regulated in an animal model of AMD (Romano et al, ). It was reported that miR‐27a could promote sprouting angiogenesis by post‐transcriptional down‐regulation of SPROUTY2, SEMA6A, and SEMA6D, which are known to be tumour suppressors (Zhou et al, ).…”

Section: Discussionsupporting

confidence: 92%

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Retinal and circulating miRNA expression patterns in diabetic retinopathy: An in silico and in vivo approach

Platania

Maisto

Trotta

et al. 2019

British J Pharmacology

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100

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Background and Purpose Diabetic retinopathy, a secondary complication of diabetes mellitus, can lead to irreversible vision loss. Currently, no treatment is approved for early phases of diabetic retinopathy. Modifications of the expression pattern of miRNAs could be involved in the early retinal damage of diabetic subjects. Therefore, we aimed at identification of dysregulated miRNAs–mRNA interactions that might be biomarkers and pharmacological targets for diagnosis and treatment of early diabetic retinopathy. Methods A focused set of miRNAs was predicted through a bioinformatic analysis accessing to Gene Expression Omnibus dataset and enrichment of information approach (GENEMANIA‐Cytoscape). Identification of miRNAs–mRNA interactions was carried out with miRNET analysis. Diabetes was induced in C57BL6J mice by streptozotocin and samples analysed at 5 and 10 weeks after diabetes induction. Retinal ultrastructure of diabetic mice was analysed through electron microscopy. We used Real‐time PCR, western blot analysis, elisa, and immunohistochemistry to study expression of miRNAs and possible targets of dysregulated miRNAs. Key Results We found that miR‐20a‐5p, miR‐20a‐3p, miR‐20b, miR‐106a‐5p, miR‐27a‐5p, miR‐27b‐3p, miR‐206‐3p, and miR‐381‐3p were dysregulated in the retina and serum of diabetic mice. VEGF, brain‐derived neurotrophic factor (BDNF), PPAR‐α, and cAMP response element‐binding protein 1 (CREB1) are targets of dysregulated miRNAs, which then modulated protein expression in diabetic retina. We found structural modifications in retinas from diabetic mice. Conclusions and Implications Serum and retina of diabetic mice express eight dysregulated miRNAs, which modified the expression of VEGF, BDNF, PPAR‐α, and CREB1, before vasculopathy in diabetic retinas.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Retinal and circulating miRNA expression patterns in diabetic retinopathy: An in silico and in vivo approach

Platania

Maisto

Trotta

et al. 2019

British J Pharmacology

Self Cite

100

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“…As a complex, multifactorial, and progressive disease, AMD is linked with both genetic (including complement) and environmental risk factors [155]. Certain miRNAs associated with the complement factor H (CFH)-mediated inflammatory degeneration and neovascularization are dysregulated in the circulating blood or ocular tissues isolated from AMD patients [118,121,156,157]. Two studies identified differential sets of miRNAs altered in plasma collected from wet AMD patients compared to healthy subjects [118,156].…”

Section: Mirnas In Neovascular Age-related Macular Degeneration (Wet mentioning

confidence: 99%

“…Some miRNAs are altered in both AMD patients and pre-clinical models of AMD, including Let-7, miR-126, and miR-21, all of which are implicated in angiogenic pathways [118][119][120][121]. The Let-7 family, upregulated in AMD patients [118,119], is pro-angiogenic and acts through the inhibition of anti-angiogenic factors tissue inhibitor of metalloproteinase-1 (TIMP-1) and thrombospondin-1 (TSP-1) [84,86,120].…”

Section: Mirnas In Neovascular Age-related Macular Degeneration (Wet mentioning

confidence: 99%

“…The Let-7 family, upregulated in AMD patients [118,119], is pro-angiogenic and acts through the inhibition of anti-angiogenic factors tissue inhibitor of metalloproteinase-1 (TIMP-1) and thrombospondin-1 (TSP-1) [84,86,120]. miR-126 and miR-21, both angiomiRs [89][90][91][92]126], are downregulated in the blood samples of AMD patients [118,121], suggesting the dysregulation of angiogenic effects in these patients. Additionally, in experimental models of CNV, miR-126 regulates CNV lesion size [122,123].…”

Section: Mirnas In Neovascular Age-related Macular Degeneration (Wet mentioning

confidence: 99%

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MicroRNAs in Vascular Eye Diseases

Liu

Huang

Britton

et al. 2020

IJMS

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Since the discovery of the first microRNA (miRNA) decades ago, studies of miRNA biology have expanded in many biomedical research fields, including eye research. The critical roles of miRNAs in normal development and diseases have made miRNAs useful biomarkers or molecular targets for potential therapeutics. In the eye, ocular neovascularization (NV) is a leading cause of blindness in multiple vascular eye diseases. Current anti-angiogenic therapies, such as anti-vascular endothelial growth factor (VEGF) treatment, have their limitations, indicating the need for investigating new targets. Recent studies established the roles of various miRNAs in the regulation of pathological ocular NV, suggesting miRNAs as both biomarkers and therapeutic targets in vascular eye diseases. This review summarizes the biogenesis of miRNAs, and their functions in the normal development and diseases of the eye, with a focus on clinical and experimental retinopathies in both human and animal models. Discovery of novel targets involving miRNAs in vascular eye diseases will provide insights for developing new treatments to counter ocular NV.

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miRNAexpression profile of retinal pigment epithelial cells under oxidative stress conditions

et al. 2018

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Deep analysis of regulative mechanisms of transcription and translation in eukaryotes could improve knowledge of many genetic pathologies such as retinitis pigmentosa ( RP ). New layers of complexity have recently emerged with the discovery that ‘junk’ DNA is transcribed and, among these, miRNAs have assumed a preponderant role. We compared changes in the expression of mi RNA s obtained from whole transcriptome analyses, between two groups of retinal pigment epithelium ( RPE ) cells, one untreated and the other exposed to the oxidant agent oxidized low‐density lipoprotein (ox LDL ), examining four time points (1, 2, 4 and 6 h). We found that 23 mi RNA s exhibited altered expression in the treated samples, targeting genes involved in several biochemical pathways, many of them associated to RP for the first time, such as those mediated by insulin receptor signaling and son of sevenless. Moreover, five RP causative genes ( KLHL7 , RDH11 , CERKL , AIPL1 and USH1G ) emerged as already validated targets of five altered mi RNA s (hsa‐miR‐1307, hsa‐miR‐3064, hsa‐miR‐4709, hsa‐miR‐3615 and hsa‐miR‐637), suggesting a tight connection between induced oxidative stress and RP development and progression. This mi RNA expression analysis of oxidative stress‐induced RPE cells has discovered new regulative functions of mi RNA s in RP that should lead to the discovery of new ways to regulate the etiopathogenesis of RP .

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Retinal and Circulating miRNAs in Age-Related Macular Degeneration: An In vivo Animal and Human Study

Cited by 88 publications

References 68 publications

Retinal and circulating miRNA expression patterns in diabetic retinopathy: An in silico and in vivo approach

Retinal and circulating miRNA expression patterns in diabetic retinopathy: An in silico and in vivo approach

MicroRNAs in Vascular Eye Diseases

miRNAexpression profile of retinal pigment epithelial cells under oxidative stress conditions

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