Maity-Kumar et al provide extensive characterization of a new mouse model for the Allan-Herndon-Dudley syn-drome (AHDS).
The BET PROTAC inhibitor dBET6 protects against retinal degeneration and inhibits the cGAS-STING in response to light damage
The cell death in retinal degenerative diseases, such as age-related macular degeneration (AMD) or
retinitis pigmentosa (RP), is often caused by the body’s own immune system, which attacks retinal cells. In this study, Zhu et al discuss the effects of a compound called dBET6 against retinal degeneration in response to light damage. dBET6 inhibits a molecular pathway of the innate immune system known as cGAS-STING. The research demonstrates that dBET6 treatment effectively prevents retinal degeneration and reduces inflammation in the retina caused by exposure to excessive light. The study suggests that dBET6 could potentially be used as a therapeutic agent to mitigate retinal degenerative conditions and offers insights into the underlying mechanisms involved in light-induced retinal damage.
CRISPR-mediated optogene expression from a cell-specific endogenous promoter in retinal ON-bipolar cells to restore vision
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
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
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
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.
Journal Club: Postsynaptic Neuronal Activity Promotes Retinal Axon Regeneration
This Journal Club provides insights into mechanisms that promote retinal ganglion cell (RGC) axon regeneration in vertebrates after optic nerve injury.
ARVO Meeting 2023 in New Orleans | April 23-27
Meet us at the 2023 ARVO Meeting in New Orleans, La. and see our OptoDrum, Photorefractor and Keratometer in action! April 23 – 27
Journal Club: Inherited Retinal Dystrophy: Chronic Proinflammatory Signaling Accelerates the Rate of Degeneration
T.J. Hollingsworth presents his work where he characterized a new polygenic mouse model of inherited retinal dystrophies, the BXD32 mouse strain. He presents evidence that a proinflammatory environment in the retina supports and accelerates the degeneration of the retina and the loss of visual function.