Influence of visual input on neuronal signaling in myopia

Emory University, Atlanta GA

Investigators

Abstract

Myopia, or nearsightedness, is increasing at an alarming rate and reaching epidemic levels worldwide. Despite optical correction, myopia increases the risk of developing blinding diseases so there is a critical need to understand the underlying pathways that regulate its progression for effective prevention. Spending time indoors is associated with more myopia progression whereas spending time in bright, outdoor environments is protective. However, an effective explanation is still lacking for how these environments directly influence myopigenesis because different environments are comprised of many visual cues, all of which have associations with myopia. Importantly, all visual scenes are composed of bright and dark features and the visual system encodes these features using the ON and OFF retinal pathways, respectively, through which all visual information is processed. Broad disruption of ON pathways can influence myopia development but accumulating evidence suggests that OFF pathways, or the signaling balance between the two pathways, may also be important. Additionally, ambient light level is strongly associated with myopia progression and modulates ON and OFF visual signaling differently. Currently, it is unknown how ON and OFF pathway signaling is affected in myopic eyes or the role of ON/OFF signaling balance in myopia susceptibility across light levels. This proposal will address these gaps in knowledge to increase our understanding of the visual pathways that regulate myopia development. Preliminary data suggests that experimentally-induced myopia or exposure to myopigenic stimuli affects ON and OFF pathways very differently, potentially altering ON/OFF retinal balance. Therefore, the hypothesis that disrupted ON/OFF signaling balance initiates and drives myopia development will be tested. First, single-cell electrophysiological recordings from ON and OFF pathways will be performed in isolated retinas and compared between myopic and non-myopic eyes to determine which pathways are most impacted. Second, ON and OFF retinal pathway balance will be disrupted in different lighting conditions while monitoring myopia susceptibility. In Aim 1, quantification of ON and OFF signals from inner retinal neurons will be obtained in dim and bright ambient light conditions. In Aim 2, quantification of ON and OFF ganglion cell receptive field signals will be obtained to determine the extent of myopic changes in retinal output neurons. In Aim 3, ON/OFF retinal balance will be disrupted in multiple lighting conditions with exposure to ON or OFF visual stimuli or pharmacological agents. Myopia susceptibility and ocular biometry will be monitored throughout the disruption. The expected outcomes of this proposal will provide powerful insight into what visual pathways are implicated in myopia progression and may help inform which visual environments are optimal to preserve retinal signaling balance for myopia interventions. This proposal aligns with the mission statement of the National Eye Institute by investigating mechanisms underlying visual disease that may aid in the development of new preventative methods.