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RESEARCH PRODUCT
Chronic social defeat stress causes retinal vascular dysfunction
Maoren WangMaoren WangYue RuanMarianne B. MüllerMarianne B. MüllerTim Van BeersKarl MerciecaVerena ProkoschHarald Von PeinMarija MilicAdrian GerickeHanhan LiuSubao Jiangsubject
MaleRetinal Ganglion CellsIntraocular pressuremedicine.medical_specialtyCell SurvivalRetinal ArteryVideo RecordingVideo microscopyRetinal ganglionSocial DefeatMiceTonometry OcularCellular and Molecular Neurosciencechemistry.chemical_compoundRetinal DiseasesCorticosteroneInternal medicineAnimalsMedicineChronic stressIntraocular PressureTranscription Factor Brn-3ARetinaDisorder of Sex Development 46XYAdrenal Hyperplasia CongenitalEndothelin-1business.industryOptic NerveRetinalActinsSensory SystemsMice Inbred C57BLDisease Models AnimalOphthalmologyEndocrinologymedicine.anatomical_structurechemistryChronic DiseaseOptic nerveOcular Hypertensionsense organsCorticosteronebusinessStress Psychologicaldescription
Abstract Purpose The roles of vascular dysfunction and chronic stress have been extensively discussed in the pathophysiology of glaucoma. Our aim was to test whether chronic stress causes retinal vascular dysfunction and therewith induces retinal ganglion cells (RGCs) loss. Methods Twelve mice underwent chronic social defeat (CSD) stress, while 12 mice received control treatment only. Intraocular pressure (IOP) was measured with a rebound tonometer. Blood plasma corticosterone concentration and adrenal gland weight were used to assess stress levels. Brn-3a staining in retinas and PPD staining in optic nerve cross sections were conducted to assess the survival of RGCs and axons respectively. The ET-1 and α-SMA levels were determined in retina. Retinal vascular autoregulation, functional response to various vasoactive agents and vascular mechanics were measured using video microscopy. Results No significant difference in IOP levels was observed during and after CSD between CSD mice and controls. CSD stress caused hypercortisolemia 2 days post-CSD. However, increased corticosterone levels went back to normal 8 months after CSD. CSD-exposed mice developed adrenal hyperplasia 3 days post-CSD, which was normalized by 8 months. RGC and axon survival were similar between CSD mice and controls. However, CSD stress caused irreversible, impaired autoregulation and vascular dysfunction of retinal arterioles in CSD mice. In addition, impaired maximal dilator capacity of retinal arterioles was observed 8 months post-CSD rather than 3 days post-CSD. Remarkably, ET-1 levels were increased 3 days post-CSD while α-SMA levels were decreased 8 months post-CSD. Conclusions We found that CSD stress does not cause IOP elevation, nor loss of RGCs and their axons. However, it strikingly causes irreversible impaired autoregulation and endothelial function in murine retinal arterioles. In addition, CSD changed vascular mechanics on a long-term basis. Increased ET-1 levels and loss of pericytes in retina vessels may involve in this process.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-12-01 | Experimental Eye Research |