6533b82afe1ef96bd128c1dd

RESEARCH PRODUCT

Melanocortin receptor agonists MCR1-5protect photoreceptors from high-glucose damage and restore antioxidant enzymes in primary retinal cell culture

Carlo GesualdoMichele D'amicoPaolo GriecoSettimio RossiClara Di FilippoFrancesco TestaJorge Miquel BarciaRosa MaistoMaria Consiglia TrottaFrancesca Simonelli

subject

Male0301 basic medicineOpsinmedicine.medical_specialtyChemokineBlotting WesternPrimary Cell CultureEnzyme-Linked Immunosorbent AssayBiologyNeuroprotection03 medical and health scienceschemistry.chemical_compound0302 clinical medicineMelanocortin receptorInternal medicinemedicineReceptoroxidative streGlutathione PeroxidaseRetinaStaining and LabelingAnimalSuperoxide DismutaseReceptors Melanocortinmelanocortin receptor agonistRetinalCell BiologyphotoreceptorImmunohistochemistryNeuroprotectionprimary retinal cell cultureMice Inbred C57BLGlucoseOpsin030104 developmental biologymedicine.anatomical_structureEndocrinologyGene Expression Regulationchemistrybiology.proteinMolecular MedicineAntioxidantMelanocortinhyperglycaemia030217 neurology & neurosurgeryPhotoreceptor Cells Vertebrate

description

Retinal photoreceptors are particularly vulnerable to local high-glucose concentrations. Oxidative stress is a risk factor for diabetic retinopathy development. Melanocortin receptors represent a family of G-protein-coupled receptors classified in five subtypes and are expressed in retina. Our previous data indicate that subtypes 1 and 5 receptor agonists exert a protective role on experimental diabetic retinopathy. This study focuses on their role in primary retinal cell cultures in high-glucose concentrations. After eye enucleation from wild-type male C57BL/6 mice, retinal cells were isolated, plated in high-glucose concentration and treated with melanocortin receptors 1 and 5 agonists and antagonists. Immunocytochemical and biochemical analysis showed that treatment with melanocortin receptors 1 and 5 agonists reduced anti-inflammatory cytokines and chemokines and enhanced manganese superoxide dismutase and glutathione peroxidase levels, preserving photoreceptor integrity. According with these evidences, we propose a major role of melanocortin receptors 1 and 5 on primary retinal cell response against high glucose or oxidative insults. Retinal photoreceptors are particularly vulnerable to local high-glucose concentrations. Oxidative stress is a risk factor for diabetic retinopathy development. Melanocortin receptors represent a family of G-protein-coupled receptors classified in five subtypes and are expressed in retina. Our previous data indicate that subtypes 1 and 5 receptor agonists exert a protective role on experimental diabetic retinopathy. This study focuses on their role in primary retinal cell cultures in high-glucose concentrations. After eye enucleation from wild-type male C57BL/6 mice, retinal cells were isolated, plated in high-glucose concentration and treated with melanocortin receptors 1 and 5 agonists and antagonists. Immunocytochemical and biochemical analysis showed that treatment with melanocortin receptors 1 and 5 agonists reduced anti-inflammatory cytokines and chemokines and enhanced manganese superoxide dismutase and glutathione peroxidase levels, preserving photoreceptor integrity. According with these evidences, we propose a major role of melanocortin receptors 1 and 5 on primary retinal cell response against high glucose or oxidative insults.

https://doi.org/10.1111/jcmm.13036