Melatonin prevents experimental central serous chorioretinopathy in rats

Abstract

Central serous chorioretinopathy (CSC) is a vision‐threatening disease with no validated treatment and unclear pathogenesis. It is characterized by dilation and leakage of choroidal vasculature, resulting in the accumulation of subretinal fluid, and serous detachment of the neurosensory retina. Numerous studies have demonstrated that melatonin had multiple protective effects against endothelial dysfunction, vascular inflammation, and blood–retinal barrier (BRB) breakdown. However, the effect of melatonin on CSC, and its exact pathogenesis, is not well understood thus far. In this study, an experimental model was established by intravitreal injection of aldosterone in rats, which mimicked the features of CSC. Our results found that melatonin administration in advance significantly inhibited aldosterone‐induced choroidal thickening and vasodilation by reducing the expression of calcium‐activated potassium channel KCa2.3, and attenuated tortuosity of choroid vessels. Moreover, melatonin protected the BRB integrity and prevented the decrease in tight junction protein (ZO‐1, occludin, and claudin‐1) levels in the rat model induced by aldosterone. Additionally, the data also showed that intraperitoneal injection of melatonin in advance inhibited aldosterone‐induced macrophage/microglia infiltration, and remarkably diminished the levels of inflammatory cytokines (interleukin‐6 [IL‐6], IL‐1β, and cyclooxygenase‐2), chemokines (chemokine C–C motif ligand 3, and C–X–C motif ligand 1), and matrix metalloproteinases (MMP‐2 and MMP‐9). Luzindole, as the nonselective MT1 and MT2 antagonist, and 4‐phenyl‐2‐propionamidotetraline, as the selective MT2 antagonist, neutralized the melatonin‐induced inhibition of choroidal thickening and choroidal vasodilation, indicating that melatonin might exert the effects via binding to its receptors. Furthermore, the IL‐17A/nuclear factor‐κB signaling pathway was activated by intravitreal administration of aldosterone, while it was suppressed in melatonin‐treated in advance rat eyes. This study indicates that melatonin could serve as a promising safe therapeutic strategy for CSC patients.

Anti‐PANoptosis is involved in neuroprotective effects of melatonin in acute ocular hypertension model

“…After dilution with normal saline, the alcohol concentration in the final melatonin solvent was 0.5%. Melatonin (20 mg/kg/day) or normal saline containing 0.5% ethanol (vehicle control) was administered by intraperitoneal injection to mice daily at 8:00 p.m 31,41 . The duration of melatonin treatment depends on the time of retinal extraction in mice, that is, 1 day, 3 days, 7 days, or 14 days for different experiments.…”

“…After dilution with normal saline, the alcohol concentration in the final melatonin solvent was 0.5%. Melatonin (20 mg/kg/day) or normal saline containing 0.5% ethanol (vehicle control) was administered by intraperitoneal injection to mice daily at 8:00 p.m. 31,41…”

Microglia: The breakthrough to treat neovascularization and repair blood-retinal barrier in retinopathy

“…Aldosterone further binds to mineralocorticoid receptor ( MR ) regulating internal water-electrolyte balance and influencing cardiovascular diseases ( Waanders et al, 2011 ). In addition, the aldosterone with the intravitreal injection can mimic clinical symptoms of central serous chorioretinopathy (CSC; Yu et al, 2022 ).…”

“…In addition, CSC is characterized by the dilation and leakage of choroidal vasculature leading to the accumulation of subretinal fluid and serous detachment of the neurosensory retina which can mimic by using aldosterone with the intravitreal injection ( Zhao et al, 2012 ; Yu et al, 2022 ). CSC may be associated with inappropriate activation of MR ( Zhao et al, 2017 ).…”

Central serous chorioretinopathy

“…MCP-1 is one of the key chemokines that regulate the migration and infiltration of monocytes/macrophages. In a recent study involving an animal model of CSC induced by intravitreal aldosterone, pretreatment with melatonin reduced choroidal thickening and vasodilation as well as macrophage/microglial infiltration,[ 54 ] supporting the view that inflammatory component may appear as the disease evolves. [ 53 ] Sirakaya et al .…”