FROM DARKNESS TO VISION: MODELS OF LASER-INDUCED RETINAL INJURY TO STUDY REGENERATION

From darkness to vision: models of laser-induced retinal injury to study regeneration:
Retinal degenerative diseases are complex multifactorial diseases with different etiological aspects but common degeneration pattern. Progressive retinal pigment epithelium and/or photoreceptors death results in irreversible vision loss due to the formation of a glial scar in mammals as a result of the activation, proliferation and extension of hypertrophied processes by Müller cells as well as expression of active factors like extracellular matrix components. On the other hand, organisms with high regenerative potential like zebrafish, possess the ability to regenerate functional retinal tissue through activation, dedifferentiation and asymmetric division of Müller cells. With our study we intend to identify uncharacterized key genes and regulatory pathways that could be modulated to induce regeneration in mammals in order to set the base for the development of regenerative therapies for incurable eye diseases. For this, we set up two models of laser induced retinal degeneration (zebrafish and mouse) using a 532 nm laser system (Micron V, Phoenix). We monitored the progression and kinetics of scar formation/resolution using optical coherence tomography imaging, histological and immunohistological analyses at different time points. We optimized laser power and pulse duration to induce replicable damages without altering the Bruch’s membrane integrity to model dry age-related macular degeneration retinal lesions. We characterized the expression of known markers (GFAP, Vimentin) indicating activation of Müller cells upon damage. Omics technologies will now be implemented to characterize the kinetics more at a molecular level and identify druggable targets.