RT Journal Article SR Electronic T1 Retinal microvascular and neuronal pathologies probed in vivo by adaptive optical two-photon fluorescence microscopy JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.11.23.517628 DO 10.1101/2022.11.23.517628 A1 Zhang, Qinrong A1 Yang, Yuhan A1 Cao, Kevin J. A1 Chen, Wei A1 Paidi, Santosh A1 Xia, Chun-Hong A1 Kramer, Richard H. A1 Gong, Xiaohua A1 Ji, Na YR 2022 UL http://biorxiv.org/content/early/2022/11/23/2022.11.23.517628.abstract 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 synapses 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 and observed microglial migration 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.Competing Interest StatementThe authors have declared no competing interest.