Upregulation of rod ribbon synapse components implies homeostatic presynaptic scaling in early‐stage retinitis pigmentosa

• DOI: 10.1111/aos.17333
• Publication Date: 2025-01-20T00:37:21Z
• Authors: Elias Roihuvuo; Marcin Tabaka; Ahmed Montaser; Elliot Choi; Krzysztof Palczewski; Frans Vinberg; Henri Leinonen
• Keywords: Ribbon; Homeostatic plasticity

Aims/Purpose: Photoreceptor death triggers retinal rewiring and remodeling that are generally thought to be detrimental for vision. Some recent research results challenge this dogma. It was recently shown in early‐stage retinitis pigmentosa (RP), the retina compensates reduced rod population activity by upscaling synaptic transmission between remaining rods bipolar cells. The purpose of current project is study molecular mechanism behind phenomenon. Methods: To model primary pathology, P23H mouse autosomal dominant RP used. Notably, wild‐type mice were not used as controls, instead, cone‐transducin (GNAT2) knockout lack cone photoreceptor functionality produce “rod‐function‐only” mice, Gnat2 ‐/‐ cross‐bred. Single cell RNA‐sequencing (scRNA‐seq; , n = 4; P23H/ 4) global proteomics ( 5; 10) analyses performed at P30. Statistical significance set q < 0.05. Additional protein expression proteins using immunohistochemistry immunoblotting. Results: ScRNA‐seq analysis revealed upregulation several major ribbon synapse genes exclusively rods. These included crucial presynaptic structure neurotransmitter release, such Ca 2+ sensor Syt1 snare complex component Snap25 Ctbp2 vesicle Sv2b . In addition, glutamate transporter Slc1a2 found. Based on data, STX1B SYT7 overexpressed whole retinas compared controls. Conclusions: Early‐stage associates with increased components play a role release. imply regulation release may improving during RP.