Therapeutic Potential of Arginase 1 for Trauma-Induced Vision Loss
Abstract
This proposal seeks to develop an effective therapy to limit retinal neurovascular injury and promote repair after potentially blinding traumatic injury to the brain or eye. Ocular injuries are a significant problem for service members and are associated with substantial costs for resources, rehabilitation, and training. So far, there is no effective treatment. The lack of understanding of the mechanisms by which trauma damages retinal neurons represents a critical knowledge gap in developing effective therapies. Our group is studying the role of an enzyme called arginase 1 in this pathological process. We have shown that arginase 1 protects against injury and promotes repair in models of acute glaucoma and optic nerve crush (ONC). Our studies using a stable, long-acting form of human recombinant arginase 1 (PEGArg1) have shown that PEGArg1 protects against retinal neuronal injury by decreasing inflammation and increasing repair functions by resident retinal immune cells. During the first year of DOD support, we have used a mouse model to elucidate the mechanisms of PEGArg1-mediatedprotection against ONC-induced injury and vision loss. Our data support the hypothesis that PEGArg1 limits neuronal injury by activating its downstream target, the ornithine decarboxylase enzyme that processes the arginase product ornithine, leading to polyamine formation. We have also assessed whether PEGArg1 can limit retinal injury and vision loss in a model of TON. We have reported the results of these studies at national and regional scientific meetings.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2023
- Accession Number
- AD1213942
Entities
People
- Ruth B. Caldwell
Organizations
- Augusta University