MACULA Conference 2022 Part 2: Proliferative Vitreoretinopathy

Saagar Pandit, MD
New York University Ophthalmology

Dr. Leo A. Kim joined us virtually from Massachusetts Eye & Ear to share an update about his research studying pharmacologic approaches in inhibiting proliferative vitreoretinopathy (PVR). As we all are aware, PVR formation is the leading cause of retinal detachment surgery failure and is the bane of a vitreoretinal surgeon’s existence.  Dr. Kim’s team utilizes in vitro models, explanted cells, and animal models using patient-derived PVR membranes to understand the pathophysiology and identify potential molecular targets to prevent the formation of PVR.

Courtesy of Leo Kim, MD, PhD

There are two important targets that his research has identified. First, runt-related transcription factor 1 (RUNX1) is a gene which has been found to be highly expressed in human-derived PVR membranes. Second, rho-kinase may have a role in PVR development, which is interesting given the recent advent of rho-kinase inhibitors for the use of intraocular pressure reduction. Both of these targets have been found to be mediators in regulating PVR formation. RUNX1 and rho-kinase work together to regulate epithelial mesenchymal transition (EMT), the process by which retinal cells migrate and transdifferentiate to form fibroglial contractile membranes that are involved in PVR formation.

Courtesy of Leo Kim, MD, PhD

Interestingly, Dr. Kim’s team used an intravitreal injection of human-derived PVR cells in a rabbit model to study PVR formation. A few weeks subsequent to intravitreal injection, fundus examination demonstrated focal areas of traction and optical coherence tomography demonstrated clumps of fibroglial cells overlying the optic nerve and retinal surface which eventually formed sheets of preretinal fibrovascular tissue. After developing the animal model, he demonstrated that RUNX1 and rho-kinase inhibition both resulted in diminished EMT and thereby decreased PVR formation. Explant models showed similar findings. Dr. Kim’s research potentially implicates RUNX1 and rho-kinase as molecular targets to help prevent PVR formation. We look forward to further developments by his team.