Abstract

Age-related macular degeneration and inherited retinal diseases are pathologies of the back of the eyes leading to
visual impairment and often total blindness. Although much progress has been made in understanding ocular
anatomy and disease pathophysiology, there is still a need for effective therapeutic interventions1,2. Recently, we
demonstrated that 7,8-dihydroxyflavone (7,8-DHF), restores vision in a zebrafish model of inherited blindness3. 7,8-
DHF is brain derived neurotrophic factor (BDNF) mimetic, able to positively stimulate the TrkB pathway with
consequent cell survival and proliferation4. However, recent reports question the direct agonism of the TrkB
receptor in vitro5. Thus, the molecular mechanism by which 7,8-DHF restores vision remain unclear. Furthermore,
we generated data suggesting systemic delivery of 7,8-DHF in mice did not result in high levels in the retina
warranting alternative delivery system for ocular drug availability (unpublished).
Indeed, the eye is a particularly challenging tissue in terms of drug delivery: various barriers from tear dilutions to
blood-retinal barrier make the retina a difficult tissue to reach. Several routes (Fig.2) can be used to reach the
retina, such as topical, systemic and intraocular injections 6. Here we investigate the mechanism by which 7,8-
DHF restores vision and use Poly D-L(lactide-co-glycolide), PLGA, an FDA approved polymer, for the formulation
of 7,8-DHF nano/microparticles7.