miRNA-124 Prevents Rat Diabetic Retinopathy by Inhibiting the Microglial Inflammatory Response
Diabetic retinopathy (DR) is characterized by vasoregression and glial activation. miRNA-124 (miR-124) reduces retinal microglial activation and alleviates vasoregression in a neurodegenerative rat model. Our aim was to determine whether miR-124 affects vascular and neural damage in the early diabet...
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| Format: | Article |
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/3/2291 |
| _version_ | 1797624396337119232 |
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| author | Ying Chen Andrea Schlotterer Luke Kurowski Lin Li Marcus Dannehl Hans-Peter Hammes Jihong Lin |
| author_facet | Ying Chen Andrea Schlotterer Luke Kurowski Lin Li Marcus Dannehl Hans-Peter Hammes Jihong Lin |
| author_sort | Ying Chen |
| collection | DOAJ |
| description | Diabetic retinopathy (DR) is characterized by vasoregression and glial activation. miRNA-124 (miR-124) reduces retinal microglial activation and alleviates vasoregression in a neurodegenerative rat model. Our aim was to determine whether miR-124 affects vascular and neural damage in the early diabetic retina. Diabetes was induced in 8-week-old <i>Wistar</i> rats by streptozotocin (STZ) injection. At 16 and 20 weeks, the diabetic rats were intravitreally injected with miR-124 mimic, and retinae were analyzed at 24 weeks. Microvascular damage was identified by evaluating pericyte loss and acellular capillary (AC) formation. Müller glial activation was assessed by glial fibrillary acidic protein (GFAP) immunofluorescence staining. Microglial activation was determined by immunofluorescent staining of ionized calcium-binding adaptor molecule 1 (Iba1) in whole mount retinae. The neuroretinal function was assessed by electroretinography. The expression of inflammation-associated genes was evaluated by qRT-PCR. A wound healing assay was performed to quantitate the mobility of microglial cells. The results showed that miR-124 treatment alleviated diabetic vasoregression by reducing AC formation and pericyte loss. miR-124 blunted Müller glial- and microglial activation in diabetic retinae and ameliorated neuroretinal function. The retinal expression of inflammatory factors including <i>Tnf-α</i>, <i>Il-1β</i>, <i>Cd74</i>, <i>Ccl2</i>, <i>Ccl3</i>, <i>Vcam1</i>, <i>Tgf-β1</i>, <i>Arg1</i>, and <i>Il-10</i> was reduced by miR-124 administration. The elevated mobility of microglia upon high glucose exposure was normalized by miR-124. The expression of the transcription factor PU.1 and lipid raft protein Flot1 was downregulated by miR-124. In rat DR, miR-124 prevents vasoregression and glial activation, improves neuroretinal function, and modulates microglial activation and inflammatory responses. |
| first_indexed | 2024-03-11T09:41:48Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:41:48Z |
| publishDate | 2023-01-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5f5f34de6ff04081898ff0b205e14a932023-11-16T16:55:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01243229110.3390/ijms24032291miRNA-124 Prevents Rat Diabetic Retinopathy by Inhibiting the Microglial Inflammatory ResponseYing Chen0Andrea Schlotterer1Luke Kurowski2Lin Li3Marcus Dannehl4Hans-Peter Hammes5Jihong Lin65th Medical Department, Medical Faculty Mannheim, University of Heidelberg, D-68167 Mannheim, Germany5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, D-68167 Mannheim, Germany5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, D-68167 Mannheim, GermanyDepartment of Vascular Surgery, Medical Faculty Mannheim, University of Heidelberg, D-68167 Mannheim, GermanyDepartment of Pediatrics, Medical Faculty Mannheim, University of Heidelberg, D-68167 Mannheim, Germany5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, D-68167 Mannheim, Germany5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, D-68167 Mannheim, GermanyDiabetic retinopathy (DR) is characterized by vasoregression and glial activation. miRNA-124 (miR-124) reduces retinal microglial activation and alleviates vasoregression in a neurodegenerative rat model. Our aim was to determine whether miR-124 affects vascular and neural damage in the early diabetic retina. Diabetes was induced in 8-week-old <i>Wistar</i> rats by streptozotocin (STZ) injection. At 16 and 20 weeks, the diabetic rats were intravitreally injected with miR-124 mimic, and retinae were analyzed at 24 weeks. Microvascular damage was identified by evaluating pericyte loss and acellular capillary (AC) formation. Müller glial activation was assessed by glial fibrillary acidic protein (GFAP) immunofluorescence staining. Microglial activation was determined by immunofluorescent staining of ionized calcium-binding adaptor molecule 1 (Iba1) in whole mount retinae. The neuroretinal function was assessed by electroretinography. The expression of inflammation-associated genes was evaluated by qRT-PCR. A wound healing assay was performed to quantitate the mobility of microglial cells. The results showed that miR-124 treatment alleviated diabetic vasoregression by reducing AC formation and pericyte loss. miR-124 blunted Müller glial- and microglial activation in diabetic retinae and ameliorated neuroretinal function. The retinal expression of inflammatory factors including <i>Tnf-α</i>, <i>Il-1β</i>, <i>Cd74</i>, <i>Ccl2</i>, <i>Ccl3</i>, <i>Vcam1</i>, <i>Tgf-β1</i>, <i>Arg1</i>, and <i>Il-10</i> was reduced by miR-124 administration. The elevated mobility of microglia upon high glucose exposure was normalized by miR-124. The expression of the transcription factor PU.1 and lipid raft protein Flot1 was downregulated by miR-124. In rat DR, miR-124 prevents vasoregression and glial activation, improves neuroretinal function, and modulates microglial activation and inflammatory responses.https://www.mdpi.com/1422-0067/24/3/2291miR-124microgliavasoregressiondiabetic retinopathy |
| spellingShingle | Ying Chen Andrea Schlotterer Luke Kurowski Lin Li Marcus Dannehl Hans-Peter Hammes Jihong Lin miRNA-124 Prevents Rat Diabetic Retinopathy by Inhibiting the Microglial Inflammatory Response International Journal of Molecular Sciences miR-124 microglia vasoregression diabetic retinopathy |
| title | miRNA-124 Prevents Rat Diabetic Retinopathy by Inhibiting the Microglial Inflammatory Response |
| title_full | miRNA-124 Prevents Rat Diabetic Retinopathy by Inhibiting the Microglial Inflammatory Response |
| title_fullStr | miRNA-124 Prevents Rat Diabetic Retinopathy by Inhibiting the Microglial Inflammatory Response |
| title_full_unstemmed | miRNA-124 Prevents Rat Diabetic Retinopathy by Inhibiting the Microglial Inflammatory Response |
| title_short | miRNA-124 Prevents Rat Diabetic Retinopathy by Inhibiting the Microglial Inflammatory Response |
| title_sort | mirna 124 prevents rat diabetic retinopathy by inhibiting the microglial inflammatory response |
| topic | miR-124 microglia vasoregression diabetic retinopathy |
| url | https://www.mdpi.com/1422-0067/24/3/2291 |
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