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Dose curve of Co3M based on behavioral outcome of optomotor response. The injection viral dose of  1.5 × 10⁸ vg/eye start to reach the behavioral result plateau.

LU, Q., WRIGHT, A. & PAN, Z. H. 2024. AAV dose-dependent transduction efficiency in retinal ganglion cells and functional efficacy of optogenetic vision restoration. Gene Ther.

DOI: 10.1038/s41434-024-00485-7

Accession Number: 39237697

Abstract

Optogenetics is a promising approach for restoring vision to the blind after photoreceptor degeneration. The ability to restore vision through AAV-mediated delivery of light-sensitive proteins, especially channelrhodopsins, into retinal ganglion cells has been extensively demonstrated in animal models. For clinical application, knowledge of viral dose-dependent functional efficacy is desired. In this study, using a triple-knockout blind mouse model and a highly light-sensitive channelrhodopsin variant, we evaluated viral dose-dependent vision restoration through retinal ganglion cell expression by using optomotor behavioral assays. Our results show that both the restored light sensitivity and visual acuity reached peak levels at a medial viral dose of 10⁸ vg. With increasing dose, transduction efficiency continued to increase while protein expression peaked at the dose of ~10⁹ vg and declined at higher doses. Also, a significant increase in retinal gliosis and inflammatory responses started at the dose of ~10⁹ vg, and a marked increase was observed at the dose of ~10¹⁰. These results provide valuable insights into viral dose design for clinical studies.