Whole retina light-evoked optoretinography (ORG) under different retina hydration levels: modeling of Bruch’s membrane ORGs

Modeling <i>in vivo</i> responses of neural tissue to stimuli is of great interest to neuroscience and physiology, as it helps us understand the complex processes underlying daily neuronal function. Recent advancements have been made in the study of light-evoked responses of the retina measured through optoretinography (ORG), a purely optical method that provides a noninvasive means of assessing retinal function. In particular, cellular swelling and scattering changes have been largely attributed to osmotically induced water movements between the photoreceptor outer segments and the extracellular matrix of subretinal space (SRS). To further investigate this hypothesis and confirm that light-evoked water movements contribute to the ORG signals, we expanded our previous ORG experimental protocols in mice to examine three distinct hydration states of the retina. Additionally, we refined our data collection and analysis techniques, enabling the detailed examination of changes in scattering properties in all key retinal layers. Our results demonstrate striking similarities between light-evoked responses and those evoked by blood plasma osmolarity changes (tissue hydration). Predictive models of scattering and thickness changes in Bruch's membrane (BrM) reveal that water movement across BrM is responsible for measured ORG signals in the outer retina, with the choroid playing a key role in supplying the necessary water.