Correlation between complete polypoidal regression and visual outcomes in polypoidal choroidal vasculopathy eyes receiving intravitreal aflibercept
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Modulating inflammation is critical to enhance nerve regeneration after injury. However, clinically applicable regenerative therapies that modulate inflammation have not yet been established. Here, we demonstrate synergistic effects of the combination of an HMG-CoA reductase inhibitor, statin/fluvastatin and critical components of the extracellular matrix, Matrix-Bound Nanovesicles (MBV) to enhance axon regeneration and neuroprotection after mouse optic nerve injury. Mechanistically, co-intravitreal injections of fluvastatin and MBV robustly promote infiltration of monocytes and neutrophils, which lead to RGC protection and axon regeneration. Furthermore, monocyte infiltration is triggered by elevated expression of CCL2, a chemokine, in the superficial layer of the retina after treatment with a combination of fluvastatin and MBV or IL-33, a cytokine contained within MBV. Finally, this therapy can be further combined with AAV-based gene therapy blocking anti-regenerative pathways in RGCs to extend regenerated axons. These data highlight novel molecular insights into the development of immunomodulatory regenerative therapy.
Evaluation of electrical impedance spectroscopy of bovine eyes for early detection of uveal melanoma
Uveal melanoma is the most common primary intraocular cancer in adults and is an aggressive malignancy with risk to vision and survival. Early detection and timely management of tumors may help preserve vision and reduce mortality rate but is challenging as many tumors are asymptomatic until they become large. Here, we studied the electrical properties of eyes to investigate a novel method for potentially detecting small intraocular tumors. We used finite element analysis to simulate the impact of uveal melanoma tumors on electrical impedance and current density in eye models. We also measured the impedance and current flow in the presence of inserted tissue simulating an intraocular tumor in enucleated bovine eyes and eyes in bovine head ex vivo. Our results showed that a 5 mm-diameter mass was detected inside a 32-mm diameter bovine eye by the impedance analyzer.
Long-term macular atrophy growth in neovascular age-related macular degeneration: influential factors and role of genetic variants
This retrospective cohort study aimed to assess the long-term growth and associated risk factors of macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD) treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) compounds.
A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics
For accurate perception and motor control, an animal must distinguish between sensory experiences elicited by external stimuli and those elicited by its own actions. The diversity of behaviors and their complex influences on the senses make this distinction challenging. Here, we uncover an action–cue hub that coordinates motor commands with visual processing in the brain’s first visual relay. We show that the ventral lateral geniculate nucleus (vLGN) acts as a corollary discharge center, integrating visual translational optic flow signals with motor copies from saccades, locomotion and pupil dynamics. The vLGN relays these signals to correct action-specific visual distortions and to refine perception, as shown for the superior colliculus and in a depth-estimation task. Simultaneously, brain-wide vLGN projections drive corrective actions necessary for accurate visuomotor control. Our results reveal an extended corollary discharge architecture that refines early visual transformations and coordinates actions via a distributed hub-and-spoke network to enable visual perception during action.
An anti-Hebbian model for binocular visual plasticity and its attentional modulation
Monocular deprivation during the critical period impairs the cortical structure and visual function of the deprived eye. Conversely, transient occlusion of one eye in adults enhances the predominance of that eye. This counter-intuitive effect of short-term monocular deprivation is a form of homeostatic plasticity. However, whether this sensory plasticity requires attention, and the underlying neural mechanisms remain unclear. Here, through a psychophysical experiment, we demonstrate that the deprivation effect is dramatically attenuated in the absence of attention. We develop a neural computational model incorporating the Hebbian learning rule in interocular inhibitory synapses (i.e., anti-Hebbian learning) to explain the deprivation effect. Our model predicts both the boosting of the deprived eye and its dependence on attention. Moreover, it accounts for other forms of binocular plasticity, including plasticity observed in prolonged binocular rivalry. We suggest that short-term binocular plasticity arises from the plasticity in inhibitory connections between the two monocular pathways.
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