Comparison of rat retinal ganglion cell transduction with different variations of rAAV vector

Vision is essential for perceiving the world and interpersonal communication, but at least 2.2 billion people have visual impairment or blindness. Glaucoma is the leading cause of irreversible blindness, and its pathophysiology involves the degeneration of retinal ganglion cells (RGC), critical neurons in the visual pathway. Daily eye drops and surgeries to modulate intraocular pressure are the available treatments. However, these treatments don’t stop neuronal degeneration and blindness progression in some glaucomatous patients. Gene therapy represents an alternative approach to revert RGC degeneration and variations of vectors based on recombinant adeno-associated virus (rAAV) are good candidates for transgene retinal delivery. Besides being largely used in clinical and preclinical trials, rAAV still faces some barriers, such as internal limiting membrane and vitreous humor volume dilution, that limit its efficiency when delivered intravitreally into the eye. Retinal gene therapy treatment must run parallel with a homogeneous RGC layer transduction and increasing the amount of vectors can be the way. Since the rAAV preps are usually very concentrated, the only way to increase the dose is increasing the injection volume which can cause retinal damage.