TY - JOUR TI - Retinal microvascular and neuronal pathologies probed in vivo by adaptive optical two-photon fluorescence microscopy AU - Zhang, Qinrong AU - Yang, Yuhan AU - Cao, Kevin J AU - Chen, Wei AU - Paidi, Santosh AU - Xia, Chun-hong AU - Kramer, Richard H AU - Gong, Xiaohua AU - Ji, Na A2 - Ding, Jun A2 - Chen, Lu A2 - Wei, Wei VL - 12 PY - 2023 DA - 2023/04/11 SP - e84853 C1 - eLife 2023;12:e84853 DO - 10.7554/eLife.84853 UR - https://doi.org/10.7554/eLife.84853 AB - The retina, behind the transparent optics of the eye, is the only neural tissue whose physiology and pathology can be non-invasively probed by optical microscopy. The aberrations intrinsic to the mouse eye, however, prevent high-resolution investigation of retinal structure and function in vivo. Optimizing the design of a two-photon fluorescence microscope (2PFM) and sample preparation procedure, we found that adaptive optics (AO), by measuring and correcting ocular aberrations, is essential for resolving putative synaptic structures and achieving three-dimensional cellular resolution in the mouse retina in vivo. Applying AO-2PFM to longitudinal retinal imaging in transgenic models of retinal pathology, we characterized microvascular lesions with sub-capillary details in a proliferative vascular retinopathy model, and found Lidocaine to effectively suppress retinal ganglion cell hyperactivity in a retinal degeneration model. Tracking structural and functional changes at high-resolution longitudinally, AO-2PFM enables microscopic investigations of retinal pathology and pharmacology for disease diagnosis and treatment in vivo. KW - fluorescence microscopy KW - adaptive optics KW - optical imaging KW - retinal vasculature KW - retinal degeneration KW - retinal pharmacology JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -