The Effects of Aging on Rod Bipolar Cell Ribbon Synapses
Abhishek P. Shrestha,
Nirujan Rameshkumar,
Johane M. Boff,
Rhea Rajmanna,
Thadshayini Chandrasegaran,
Courtney E. Frederick,
David Zenisek,
Thirumalini Vaithianathan
Affiliations
Abhishek P. Shrestha
Department of Pharmacology, Addiction Science, and Toxicology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA
Nirujan Rameshkumar
Department of Pharmacology, Addiction Science, and Toxicology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA
Johane M. Boff
Department of Pharmacology, Addiction Science, and Toxicology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA
Rhea Rajmanna
Department of Pharmacology, Addiction Science, and Toxicology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA
Thadshayini Chandrasegaran
Department of Zoology, Faculty of Science, University of Jaffna, Jaffna 40000, Sri Lanka
Courtney E. Frederick
Department of Molecular and Cellular Physiology, Yale University School of Medicine, New Haven, CT 06510, USA
David Zenisek
Department of Molecular and Cellular Physiology, Yale University School of Medicine, New Haven, CT 06510, USA
Thirumalini Vaithianathan
Department of Pharmacology, Addiction Science, and Toxicology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA
The global health concern posed by age-related visual impairment highlights the need for further research focused on the visual changes that occur during the process of aging. To date, multiple sensory alterations related to aging have been identified, including morphological and functional changes in inner hair cochlear cells, photoreceptors, and retinal ganglion cells. While some age-related morphological changes are known to occur in rod bipolar cells in the retina, their effects on these cells and on their connection to other cells via ribbon synapses remain elusive. To investigate the effects of aging on rod bipolar cells and their ribbon synapses, we compared synaptic calcium currents, calcium dynamics, and exocytosis in zebrafish (Danio rerio) that were middle-aged (MA,18 months) or old-aged (OA, 36 months). The bipolar cell terminal in OA zebrafish exhibited a two-fold reduction in number of synaptic ribbons, an increased ribbon length, and a decrease in local Ca2+ signals at the tested ribbon location, with little change in the overall magnitude of the calcium current or exocytosis in response to brief pulses. Staining of the synaptic ribbons with antibodies specific for PKCa revealed shortening of the inner nuclear and plexiform layers (INL and IPL). These findings shed light on age-related changes in the retina that are related to synaptic ribbons and calcium signals.