Finerenone, a Non-Steroidal Mineralocorticoid Receptor Antagonist, Reduces Vascular Injury and Increases Regulatory T-Cells: Studies in Rodents with Diabetic and Neovascular Retinopathy.
Jack R JeromeDevy DeliyantiVaraporn SuphapimolPeter KolkhofJennifer L Wilkinson-BerkaPublished in: International journal of molecular sciences (2023)
Vision loss in diabetic retinopathy features damage to the blood-retinal barrier and neovascularization, with hypertension and the renin-angiotensin system (RAS) having causal roles. We evaluated if finerenone, a non-steroidal mineralocorticoid receptor (MR) antagonist, reduced vascular pathology and inflammation in diabetic and neovascular retinopathy. Diabetic and hypertensive transgenic (mRen-2)27 rats overexpressing the RAS received the MR antagonist finerenone (10 mg/kg/day, oral gavage) or the angiotensin-converting enzyme inhibitor perindopril (10 mg/kg/day, drinking water) for 12 weeks. As retinal neovascularization does not develop in diabetic rodents, finerenone (5 mg/kg/day, i.p.) was evaluated in murine oxygen-induced retinopathy (OIR). Retinal vasculopathy was assessed by measuring gliosis, vascular leakage, neovascularization, and VEGF. Inflammation was investigated by quantitating retinal microglia/macrophages, pro-inflammatory mediators, and anti-inflammatory regulatory T-cells (Tregs). In diabetes, both treatments reduced systolic blood pressure, gliosis, vascular leakage, and microglial/macrophage density, but only finerenone lowered VEGF, ICAM-1, and IL-1ß. In OIR, finerenone reduced neovascularization, vascular leakage, and microglial density, and increased Tregs in the blood, spleen, and retina. Our findings, in the context of the FIDELIO-DKD and FIGARO-DKD trials reporting the benefits of finerenone on renal and cardiovascular outcomes in diabetic kidney disease, indicate the potential of finerenone as an effective oral treatment for diabetic retinopathy.
Keyphrases
- diabetic retinopathy
- regulatory t cells
- blood pressure
- optical coherence tomography
- type diabetes
- drinking water
- wound healing
- vascular endothelial growth factor
- oxidative stress
- dendritic cells
- inflammatory response
- angiotensin converting enzyme
- hypertensive patients
- neuropathic pain
- heart failure
- angiotensin ii
- cardiovascular disease
- endothelial cells
- adipose tissue
- left ventricular
- mass spectrometry
- lipopolysaccharide induced
- skeletal muscle
- high glucose
- risk assessment
- lps induced
- combination therapy
- climate change
- case control
- insulin resistance
- atomic force microscopy
- optic nerve
- gestational age