Jonathan Lin, MD
Massachusetts Eye and Ear
The Basic Science session of the 46th Annual Meeting of the Macula Society moderated by Drs. Mary Elizabeth Hartnett and Paul Sternberg, highlighted the incredible strides the retina research community has made towards understanding the pathophysiology of retinal diseases and potential new treatments on the horizon.
The session began with Dr. Leo Kim from Mass Eye and Ear who presented his work titled “RUNX1 Promotes Angiofibrosis through Endothelial-to-Mesenchymal Transition (Endo-MT).” His group has previously noted runt-related transcription factor 1 (RUNX1), which is well known for its role in regulating hematopoietic cell maturation, is also present in membranes isolated from patients with proliferative diabetic retinopathy. During this session, Dr. Kim shared exciting findings that RUNX1 may also promote the transition of endothelial cells to a mesenchymal phenotype and thereby contribute to pathological angiofibrosis. Inhibition of RUNX1 with a small molecule was found to reduce endothelial cell proliferation, as well as prevent pathologic angiofibrosis in an animal model.
Dr. Eric Nudleman from the University of California San Diego Shiley Eye Institute presented his work titled “Development of a Novel Mouse Model of Retinal Fibrosis Due to Ischemic Retinal Vascular Disease.” Pathological retinal fibrosis is a unifying feature of multiple blinding retinal diseases, but we do not have good animal models for this pathology. The classic oxygen-induced retinopathy (OIR) model is incomplete in that the mice do not develop retinal fibrosis. Dr. Nudleman and colleagues created a modified OIR model in which mice developed early retinal hemorrhages with subsequent plaques/scars. He speculates that this new model could be used to test future therapeutics and to advance our understanding of retinal diseases.
Dr. Ian Han from the University of Iowa presented his work titled “The Degree of AAV-induced Retinal Inflammation Varies Based on Serotype and Route of Delivery (Intravitreal, Subretinal, or Suprachoroidal) in Rats.” There is much excitement surrounding the possibility of using gene therapy to treat blinding diseases, especially with the approval of Luxturna® (voretigene neparvovec-rzyl) for Leber congenital amaurosis. A key question that remains incompletely understood is whether ocular inflammation may be triggered when the gene products are delivered to the eye. In this study, Dr. Han and colleagues performed histological characterization of the ocular inflammation related to adeno-associated virus (AAV)-mediated gene replacement in rats. They tested multiple AAV serotypes, as well as routes of delivery (intravitreal, subretinal, or suprachoroidal). Their results suggest that there is significant heterogeneity in efficiency of transduction and degree of intraocular inflammation depending on both AAV serotype and route of delivery. These studies have significant implications, as they may guide the design of future gene therapy for humans.