CRISPR-mediated optogene expression from a cell-specific endogenous promoter in retinal ON-bipolar cells to restore vision

Muriel Haag

Optogenetic restoration of visual function is a promising therapeutic avenue to restore vision after retinal degeneration. Targeted and efficient expression of optogenes, however, still proves challenging. In this study, Maddalena and Kleinlogel explored CRISPR-mediated expression of the optogene Opto-mGluR6 in retinal bipolar cells. They found, using Striatech’s OptoDrum, that treatment of otherwise blind rd1 mice improved their visual acuity significantly.

Molecular basis of impaired extraocular muscle function in a mouse model of congenital myopathy due to compound heterozygous Ryr1 mutations

Muriel Haag

Human congenital myopathies are most commonly caused by mutations in the RYR1 gene, encoding for a muscular calcium channel. In a corresponding mouse model, this study investigates the molecular basis of the
eye muscle phenotype which is part of the congenital myopathy. In the mutants, the altered calcium homeostasis and reduced calcium released by muscle fibres in the extraocular muscles lead to reduced activity of the eye muscles during development. This causes mis-expression of Myelin heavy chain (MyHC) isoforms, lack of the isoform MyHC-EO, myofibrillar disorganization, displacement and decreased number of mitochondria.

CyclinD2-mediated regulation of neurogenic output from the retinal ciliary margin is perturbed in albinism

Muriel Haag

This article is an in-depth investigation of molecular alterations underlying chiasmatic misrouting in the albino binocular circuit. During development, in a specialized retinal niche—the ciliary margin—fewer cells express the cellcycle regulator CyclinD2. Consequently, the cell cycle is elongated, resulting in fewer ipsilaterally projecting RGCs and perturbed binocular vision.

Bipolar cell targeted optogenetic gene therapy restores parallel retinal signaling and high-level vision in the degenerated retina

Muriel Haag

Kralik et al show successful optogenetic vision restoration in blind mice by expressing an engineered melanopsin-mGluR6 chimeric protein in ON bipolar cells. The treated mice show visual behavior that approaches the quality of wild type mice, shown with optomotor measurements. The responses of retinal ganglion cells are highly diverse, indicating that parallel processing is restored in treated retinas.

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