Three new circulating microRNAs may be associated with wet age-related macular degeneration

Elbay, Ahmet; Ercan, Çilem; Akbaş, Fahri; Bulut, Huri; Özdemir, Hakan

doi:10.1080/00365513.2019.1637931

Cited by 35 publications

(32 citation statements)

References 45 publications

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“…Ertekin et al 15 Plasma Wet AMD miR-17-5p, miR-20a-5p, miR-24-3p, miR-106a-5p, and miR-223-3p Grassmann et al 16 Serum Dry AMD, wet AMD Dry AMD: mir-424-5p;Wet AMD: mir-424-5p, mir-301-3p, mir-361-5p Ren et al 17 Whole blood Dry AMD, wet AMD miR-27a-3p, miR-29b-3p, miR-195-5p;Wet AMD: miR-27a Elbay et al 18 Exosomes AMD miR-486-5p, miR-626…”

Section: Introductionmentioning

confidence: 99%

Identification of Novel Serum MicroRNAs in Age-Related Macular Degeneration

Elshelmani

Wride

Saad

et al. 2020

Trans. Vis. Sci. Tech.

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Section: Introductionmentioning

confidence: 99%

Identification of Novel Serum MicroRNAs in Age-Related Macular Degeneration

Elshelmani

Wride

Saad

et al. 2020

Trans. Vis. Sci. Tech.

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“…Nowadays, miRNA research has been rocketed from 214 publications in 2014 to 11,610 in 2018 (source: Pubmed). Many clinical fields are now focused on the study of miRNA for diagnosis or treatment purposes 3,4 . Moreover, miRNAs play an important role in different cellular processes such as angiogenesis 5,6 , oxidative stress 7 , and immune responses 8 .…”

Section: Introductionmentioning

confidence: 99%

miR302a and 122 are deregulated in small extracellular vesicles from ARPE-19 cells cultured with H2O2

Oltra

Vidal-Gil

Maisto

et al. 2019

Sci Rep

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Age related macular degeneration (AMD) is a common retina-related disease leading to blindness. Little is known on the origin of the disease, but it is well documented that oxidative stress generated in the retinal pigment epithelium and choroid neovascularization are closely involved. The study of circulating miRNAs is opening new possibilities in terms of diagnosis and therapeutics. miRNAs can travel associated to lipoproteins or inside small Extracellular Vesicles (sEVs). A number of reports indicate a significant deregulation of circulating miRNAs in AMD and experimental approaches, but it is unclear whether sEVs present a significant miRNA cargo. The present work studies miRNA expression changes in sEVs released from ARPE-19 cells under oxidative conditions (i.e. hydrogen peroxide, H 2 o 2). H 2 o 2 increased sEVs release from ARPE-19 cells. Moreover, 218 miRNAs could be detected in control and H 2 o 2 induced-sEVs. Interestingly, only two of them (hsa-miR-302a and hsa-miR-122) were significantly under-expressed in H 2 o 2-induced sEVs. Results herein suggest that the down regulation of miRNAs 302a and 122 might be related with previous studies showing sEVs-induced neovascularization after oxidative challenge in ARPE-19 cells. microRNA (miRNA) are small non-coding RNA sequences (21-25 nucleotides) able to regulate the expression of one or more mRNAs 1,2. miRNAs regulate protein translation by targeting their complementary mRNAs and by repressing translation or degrading a target mRNA. Nowadays, miRNA research has been rocketed from 214 publications in 2014 to 11,610 in 2018 (source: Pubmed). Many clinical fields are now focused on the study of miRNA for diagnosis or treatment purposes 3,4. Moreover, miRNAs play an important role in different cellular processes such as angiogenesis 5,6 , oxidative stress 7 , and immune responses 8. Most of the cells can release extracellular vesicles (EVs), which may interact with both neighbouring or distant target cells 9,10. EVs typically include genetic material and proteins, making these vesicles key in cell to cell communication 11. Among these EVs, are the small EVs (sEVs; <100 nm diameter) 12 , which were observed to carry miRNAs 13. Cargo of sEVs depends on the cellular origin and the homeostatic state 14. Recent studies analysed miRNA expression in biological samples from patients with age related macular degeneration (AMD), in order to identify those miRNAs related to the pathophysiology and progression of the disease. Among these, miR-9, miR-23a, miR-27a, miR-34a, miR-146a, miR-155 have been proposed as potential candidates 15-19. The "wet" form of AMD is characterized by neovascularization 20. The retinal pigment epithelium (RPE) plays a pivotal role between the photoreceptor cell layer and the choroid, the vascular network surrounding the eye. This interaction is critical for retinal homeostasis 21. Ren and collaborators analysed circulating miRNAs from AMD patients and proposed miR-27a-3p, miR-29b-3p, and miR-195-5p as candidate biomarkers for AMD diagnosis 19....

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“…In total, six studies met these criteria [21][22][23][24][25][26]. Studies that investigated intracellular cmiRNAs [54,55], cmiRNAs in exosomes [56], a combination of nAMD and geographic atrophy AMD patients [57,58], and a combination of nAMD and congenital hemochromatosis patients [59] were excluded.…”

Section: Literture Analysis Of Differentially Expressed Cmirnas In Namentioning

confidence: 99%

A Circulating MicroRNA Profile in a Laser-Induced Mouse Model of Choroidal Neovascularization

Kiel

Berber

Karlstetter

et al. 2020

IJMS

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Choroidal neovascularization (CNV) is a pathological process in which aberrant blood vessels invade the subretinal space of the mammalian eye. It is a characteristic feature of the prevalent neovascular age-related macular degeneration (nAMD). Circulating microRNAs (cmiRNAs) are regarded as potentially valuable biomarkers for various age-related diseases, including nAMD. Here, we investigated cmiRNA expression in an established laser-induced CNV mouse model. Upon CNV induction in C57Bl/6 mice, blood-derived cmiRNAs were initially determined globally by RNA next generation sequencing, and the most strongly dysregulated cmiRNAs were independently replicated by quantitative reverse transcription PCR (RT-qPCR) in blood, retinal, and retinal pigment epithelium (RPE)/choroidal tissue. Our findings suggest that two miRNAs, mmu-mir-486a-5p and mmur-mir-92a-3p, are consistently dysregulated during CNV formation. Furthermore, in functional in vitro assays, a significant impact of mmu-mir-486a-5p and mmu-mir-92a-3p on murine microglial cell viability was observed, while mmu-mir-92a-3p also showed an impact on microglial mobility. Taken together, we report a robust dysregulation of two miRNAs in blood and RPE/choroid after laser-induced initiation of CNV lesions in mice, highlighting their potential role in pathology and eventual therapy of CNV-associated complications.

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Three new circulating microRNAs may be associated with wet age-related macular degeneration

Cited by 35 publications

References 45 publications

Identification of Novel Serum MicroRNAs in Age-Related Macular Degeneration

Identification of Novel Serum MicroRNAs in Age-Related Macular Degeneration

miR302a and 122 are deregulated in small extracellular vesicles from ARPE-19 cells cultured with H2O2

A Circulating MicroRNA Profile in a Laser-Induced Mouse Model of Choroidal Neovascularization

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