PROJECT SUMMARY Glaucoma is the leading cause of irreversible blindness worldwide. This optic neuropathy is often associated with increased intraocular pressure (IOP), and all current treatments seek to reduce IOP to prevent further vision loss. The current first-line treatment is the use of daily topical eye drop medications, which are notably associated with low adherence rates and systemic side effects. Patients may go on to require surgery, with potential for revisions and complications. Thus, improved technologies for IOP control are a pressing unmet need. We previously demonstrated that expansion of the suprachoroidal space (SCS) of the eye using a hydrogel injected via a microneedle (MN) reduces IOP for up to 4 months in rabbits, likely due to increased aqueous humor outflow through the unconventional drainage pathway. In this project, our long-term goal is to develop hydrogel-based SCS expansion as a novel glaucoma treatment complementary to topical eyedrops and surgery. As a non-drug, non-surgical method, we expect that this treatment approach can greatly improve patient adherence and treatment outcomes as compared to existing approaches. The objectives of this proposal are to: (i) more definitively elucidate the mechanism of IOP reduction due to SCS expansion; (ii) develop a hydrogel formulation that provides IOP reduction for at least 6 months after a single treatment, which will offer significant translational potential; and (iii) further investigate the safety and efficacy of this treatment method. To achieve Aim 1, we will measure changes to aqueous humor outflow through the conventional and unconventional pathways following hydrogel injections. Factors that may affect hydrogel degradation, such as ciliary muscle contraction, will also be evaluated using a pharmacologic agent that modifies ciliary muscle action in conjunction with hydrogel injection. In Aim 2, a slowly degrading enzyme-digestible hydrogel will be developed to provide a longer duration of IOP reduction that can be controlled/reversed by a healthcare provider. Aim 3 will assess the safety and efficacy of this treatment method and the feasibility of repeat injections. The outcome of this work will be a novel glaucoma treatment method for long-term IOP reduction, including evaluations in animal models, that will pave the way for future clinical trials. My training plan provides excellent mentorship under my PhD thesis advisors, Drs. Ross Ethier and Mark Prausnitz, whose expertise in glaucoma and drug delivery methods, respectively, will equip me with a strong foundation in translational vision research and advance my professional development. My collaborators will also provide guidance, such as for evaluating aqueous humor outflow in Aim 1 and hydrogel fabrication in Aim 2. I have planned for longitudinal clinical experiences during my PhD that will prepare me for the last year of my medical school and for residency training. I have intentionally chosen my thesis to ...