Noninvasive Ophthalmic Imaging Measures Retinal Degeneration and Vision Deficits in Ndufs4−/− Mouse Model of Mitochondrial Complex I Deficiency

Muriel Haag

Mitochondrial complex I disorders are a heterogeneous group of rare inherited diseases caused by mutations affecting proteins in the mitochondrial electron transport chain. Neurological and ophthalmic pathologies are common to many forms of complex I deficiency, due to the high energy demands of central nervous system tissues. Avrutsky et al characterized one such mouse model, carrying a mutation in Ndufs4 (NADH:ubiquinone oxidoreductase Fe-S pro-tein 4), which shows fast retinal degeneration within only a few weeks. They show that a range of non-invasive techniques (OCT for structural changes, ERG for electrophysiological properties, and OMR with our OptoDrum for behavioral assessment) can capture relevant measures of disease progression.

Immune responses in mice after blast-mediated traumatic brain injury TBI autonomously contribute to retinal ganglion cell dysfunction and death

Muriel Haag

Blast injuries are common in modern warfare. They lead to immediate damage to the nervous system, but often develop into chronic disease with progressive deterioration, including in the visual system. It is proposed that neuroinflammatory processes underly this chronic phase. 4 weeks after injury, Harper et al transferred splenocytes of mice exposed to blast-mediated traumatic brain injury (bTBI) into naïve animals. Those naïve animals developed visual symptoms and experienced ganglion cell dysfunction similar to the blast-injured mice, suggesting that the immune system is indeed involved in the chronic phase of bTBI.

Targeting Cholesterol Homeostasis Improves Recovery in Experimental Optic Neuritis

Muriel Haag

Chronic autoimmune diseases, such as multiple sclerosis (MS), lead to demyelination of neurons. Recovery after demyelinating events is limited by cholesterol recycling. Godwin et al show that gentasic acid (GA) treatment amelio-rates the damages in a murine model of optic nerve demyelination, MOG-induced experimental autoimmune encephalomyelitis (EAE). Improved cholesterol homeostasis may therefore contribute to rehabilitation of MS patients.

Off Starburst Amacrine Cells in the Retina Trigger Looming-Evoked Fear Responses in Mice

Muriel Haag

Looming dark stimuli (an expanding shadow) evoke evolutionary conserved fear or flight responses. This study looked at the effects on this behavior of ablating starburst amacrine cells, a specific interneuron in the retina which is involved in direction-selective retinal responses. Bohl et al found that looming-induced fear responses were eliminated when a sufficient number of OFF starburst cell were ablated. As a further behavioral readout to confirm successful starburst ablation, Bohl et al used measurements of the optomotor reflex which is known to depend on the direction-selective circuitry in the retina. OMR seemed to depend mostly on ON starburst cells, so that the two behavioral changes (OMR and looming-induced fear response) did not coincide in all mice.

Cytotoxic CNS-associated T cells drive axon degeneration by targeting perturbed oligodendrocytes in PLP1 mutant mice

Muriel Haag

This study explores the role of CD8+ T cells in conditions where the myelin sheath is damaged. These T cells specifically target and attack mutated cells responsible for producing myelin, leading to nerve damage and degeneration. They found that early treatment with a specific medication can reduce the recruitment of harmful T cells and prevent further damage. However, targeting these T cells later on is less effective. Understanding these interactions may help develop new treatments for conditions involving myelin defects and inflammation.

A visual opsin from jellyfish enables precise temporal control of G protein signalling

Muriel Haag

This research focuses on understanding how the rhodopsin protein found in a box jellyfish utilizes a unique Gαs intracellular pathway to achieve fast vision. The study uncovers a mechanism where the rhodopsin protein constitutively binds to a single downstream Gαs partner, enabling rapid activation and inactivation of G-protein signaling within milliseconds. By studying the rhodopsin protein, van Wyk and Kleinlogel engineered an optogenetic tool and used it in viral gene therapy to restore light responses in blind mice.

Postsynaptic neuronal activity promotes regeneration of retinal axons

Muriel Haag

Varadarajan et al have discovered that stimulating specific brain cells can promote the regeneration of damaged optic nerve fibers, potentially restoring lost vision. By increasing neural activity in the brain’s visual target neurons, they found that retinal ganglion cell (RGC) axons can regrow and reconnect with their proper synaptic targets. This finding highlights the importance of postsynaptic brain targets in repairing visual circuits and offers hope for developing strategies to restore vision in individuals with vision loss.

Alleviating early demyelination in ischaemia/reperfusion by inhibiting sphingosine-1-phosphate receptor 2 could protect visual function from impairment

Muriel Haag

Retinal ischemia/reperfusion (I/R) injury can cause permanent vision loss, and effective treatments are currently lacking. Xue et al have discovered that early damage to the optic nerve’s myelin sheath is a key factor in this injury. By targeting a receptor called S1PR2 and using a specific inhibitor called JTE-013, they were able to protect retinal cells, prevent demyelination, and promote visual function recovery.

Vitamin C protects retinal ganglion cells via SPP1 in glaucoma and after optic nerve damage

Lena Schadock

Li and Jacobs show that Vitamin C, administered through drinking water protects retinal ganglion cells during glaucoma and after optic nerve crush. The elucidate the pathway of Vitamin C action which involves reactive astrocytes. The positive effect of Vitamin C can be seen not only in histological examinations, but is also manifested in preserved visual acuity, as measured with Striatech’s OptoDrum.