Partial rescue of the full-field electroretinogram in patients with RPE65-related retinal dystrophy following gene augmentation therapy with voretigene neparvovec-rzyl.

Purpose: To present a series of patients with RPE65-related retinal dystrophy showing a partial rescue of the full-field electroretinogram (ERG) following gene replacement therapy with voretigene neparovec-rzyl (Luxturna®).

Methods: This retrospective chart review examined 17 patients treated with voretigene neparovec-rzyl (VN) at the Casey Eye Institute (2018-2022). The last pre-operative ERG and all available post-operative ERGs were analyzed to identify subjects with functional rescue.

Hippocampal damage causes retrograde amnesia for objects' visual, but not odour, properties in male rats.

Damage to the hippocampus produces profound retrograde amnesia, but odour and object discrimination memories can be spared in the retrograde direction. Prior lesion studies testing retrograde amnesia for object/odour discriminations are problematic due to sparing of large parts of the hippocampus, which may support memory recall, and/or the presence of uncontrolled, distinctive odours that may support object discrimination. To address these issues, we used a simple object discrimination test to assess memory in male rats.

Peptide-guided lipid nanoparticles deliver mRNA to the neural retina of rodents and nonhuman primates.

Lipid nanoparticle (LNP)-based mRNA delivery holds promise for the treatment of inherited retinal degenerations. Currently, LNP-mediated mRNA delivery is restricted to the retinal pigment epithelium (RPE) and Müller glia. LNPs must overcome ocular barriers to transfect neuronal cells critical for visual phototransduction, the photoreceptors (PRs).

An improved protocol for generation and characterization of human-induced pluripotent stem cell-derived retinal pigment epithelium cells.

We present an optimized protocol for guided differentiation of retinal pigment epithelium (RPE) cells from human-induced pluripotent stem cells (iPSC). De novo-generated RPE cells are mature, polarized, and mimic the cellular and molecular profile of primary RPE; they are also suitable for cell transplantation studies. The protocol includes an enrichment step, making it useful for large-scale GMP manufacturing.

Refinement of Spatial Receptive Fields in the Developing Mouse Lateral Geniculate Nucleus Is Coordinated with Excitatory and Inhibitory Remodeling.

Receptive field properties of individual visual neurons are dictated by the precise patterns of synaptic connections they receive, including the arrangement of inputs in visual space and features such as polarity (On vs Off). The inputs from the retina to the lateral geniculate nucleus (LGN) in the mouse undergo significant refinement during development. However, it is unknown how this refinement corresponds to the establishment of functional visual response properties.

Experience-enabled enhancement of adult visual cortex function.

We previously reported in adult mice that visuomotor experience during monocular deprivation (MD) augmented enhancement of visual-cortex-dependent behavior through the non-deprived eye (NDE) during deprivation, and enabled enhanced function to persist after MD. We investigated the physiological substrates of this experience-enabled form of adult cortical plasticity by measuring visual behavior and visually evoked potentials (VEPs) in binocular visual cortex of the same mice before, during, and after MD. MD on its own potentiated VEPs contralateral to the NDE during MD and shifted ocular dominance (OD) in favor of the NDE in both hemispheres.

Experience-induced interocular plasticity of vision in infancy.

Animal model studies of amblyopia have generally concluded that enduring effects of monocular deprivation (MD) on visual behavior (i.e., loss of visual acuity) are limited to the deprived eye, and are restricted to juvenile life.

A novel mechanism for switching a neural system from one state to another.

An animal's ability to rapidly adjust to new conditions is essential to its survival. The nervous system, then, must be built with the flexibility to adjust, or shift, its processing capabilities on the fly. To understand how this flexibility comes about, we tracked a well-known behavioral shift, a visual integration shift, down to its underlying circuitry, and found that it is produced by a novel mechanism - a change in gap junction coupling that can turn a cell class on and off.

Experience-dependent plasticity from eye opening enables lasting, visual cortex-dependent enhancement of motion vision.

Developmentally regulated plasticity of vision has generally been associated with "sensitive" or "critical" periods in juvenile life, wherein visual deprivation leads to loss of visual function. Here we report an enabling form of visual plasticity that commences in infant rats from eye opening, in which daily threshold testing of optokinetic tracking, amid otherwise normal visual experience, stimulates enduring, visual cortex-dependent enhancement (>60%) of the spatial frequency threshold for tracking. The perceptual ability to use spatial frequency in discriminating between moving visual stimuli is also improved by the testing experience.

Independent visual threshold measurements in the two eyes of freely moving rats and mice using a virtual-reality optokinetic system.

Slow horizontal head and body rotation occurs in mice and rats when the visual field is rotated around them, and these optomotor movements can be produced reliably in a virtual-reality system. If one eye is closed, only motion in the temporal-to-nasal direction for the contralateral eye evokes the tracking response. When the maximal spatial frequency capable of driving the response ("acuity") was measured under monocular and binocular viewing conditions, the monocular acuity was identical to the binocular acuity measured with the same rotation direction.