Age-related Macular Degeneration (AMD) and Retinitis Pigmentosa (RP) are vision disorders caused by loss of rod and cone photoreceptors, but downstream retinal neurons also show physiological and morphological changes, resulting in the emergence of hyperactivity and rhythmic firing in many retinal ganglion cells (RGC). We recently discovered that retinoic acid (RA) is a key signal that triggers hyperactivity and that blockers of RA unmask light responses in RGCs that would otherwise be obscured. Recent work is revealing where in the retina circuit RA initiates functional changes. Moreover, interfering with the RA signaling pathway with drug or gene therapy can improve spatial vision in a mouse model of RP, providing a new strategy for enhancing low vision in human RP and AMD.

Outside the foveola, visual acuity and other visual functions gradually deteriorate with increasing eccentricity. Humans compensate for these limitations by relying on a tight link between perception and action; rapid gaze shifts (saccades) occur 2-3 times every second, separating brief “fixation” intervals in which visual information is acquired and processed. During fixation, however, the eye is not immobile. Small eye movements incessantly shift the image on the retina even when the attended stimulus is already foveated, suggesting a much deeper coupling between visual functions and oculomotor activity. Thanks to a combination of techniques allowing for high-resolution recordings of eye position, retinal stabilization, and accurate gaze localization, we examined how attention and eye movements are controlled at this scale. We have shown that during fixation, visual exploration of fine spatial detail unfolds following visuomotor strategies similar to those occurring at a larger scale. This behavior compensates for non-homogenous visual capabilities within the foveola and is finely controlled by attention, which facilitates processing at selected foveal locations. Ultimately, the limits of high acuity vision are greatly influenced by the spatiotemporal modulations introduced by fixational eye movements. These findings reveal that, contrary to common intuition, placing a stimulus within the foveola is necessary but not sufficient for high visual acuity; fine spatial vision is the outcome of an orchestrated synergy of motor, cognitive, and attentional factors.