Age-Related Alterations in Retinal Monoamine Neuromodulation during AMD-Like Retinopathy Development in Rats

Aging is the major risk factor for age-related macular degeneration (AMD), a leading cause of vision loss in aging populations. Increasing evidence suggests that alterations of neurotransmitter systems contribute to the pathogenesis of AMD. Although biogenic amines in the retina were first detected over 50 years ago, their age-related dynamics and role in AMD development are still poorly understood. Here, we compare age-related changes in the concentrations of norepinephrine, serotonin, dopamine, and their main metabolites in the retinas of senescence-accelerated OXYS rats that develop an AMD-like retinopathy and Wistar rats. We also assessed activities of monoamine oxidases (MAOs) and tyrosine hydroxylase and compared changes in these activities with transcriptome data on genes associated with biogenic amine pathways. The results revealed that in OXYS rats, retinal aging and progression of AMD-like retinopathy are primarily associated with alterations in the dopaminergic system. Specifically, dopamine and its main metabolite DOPAC were present in the retinas at higher levels than serotonin and 5-hydroxyindoleacetic acid. Furthermore, the development of retinopathy in OXYS rats was accompanied by elevated dopamine and DOPAC levels, decreased MAO activity, and changes in the expression of genes associated with the dopaminergic synapse signaling.