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Research Lecture Series Dr. Louis R. Pasquale Presents: The Role of Nitric Acid Signaling in Glaucomatous Neuro-Degeneration

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Please join Dr. Louis R. Pasquale, MD, FARVO, as he presents, “The Role of Nitric Acid Signaling in Glaucomatous Neuro-Degeneration.” The lecture will take place on September 18, 2018 as part of the Research Lecture Series in Lecture Hall 2. All are welcome to attend. One hour of Mass CE will be awarded. You are invited to join us for a light reception in Conference Room 1 following the lecture.

Abstract: Patients with POAG demonstrate impairments in retinal vascular autoregulation, blunted brachial artery vasodilation in response to acetylcholine (the universal vasodilator), retinal and nailfold capillary hemodynamic abnormalities, and nailfold capillary morphological abnormalities indicative of impaired nitric oxide (NO) signaling.  Multiple genetic epidemiology studies implicate impaired nitric oxide – guanylate cyclase-1 – cyclic guanylate monophosphate (NO-GC1–cGMP) signaling as a possible pathogenic mechanism in POAG and PACG. Since the nitric oxide signaling pathway is rich in drug targets, we hypothesized that enhancing intracellular cGMP levels could be neuroprotective in glaucoma. We boosted cGMP signaling by administering the PDE5 inhibitor, tadalafil orally (10 mg/kg/day) in two murine model of glaucoma – primary open angle glaucoma (POAG; GC-1-/- mice) and primary angle-closure glaucoma (PACG; Microbead Occlusion Model) - and measured RGC viability at both the soma and axon level.Collectively our findings suggest that enhancement of the NO-GC-1-cGMP pathway protects the RGC body and axon in murine models of POAG and PACG, and that enhanced signaling through this pathway may serve as a novel glaucoma treatment, acting independently of IOP.  Future work to show that tadalafil preserves visual function in these glaucoma models as well as dose ranging experiments would set the stage for a randomized clinical trial for tadalafil use in glaucoma patients.