Regenerative Lipids in Traumatic Glaucomatous Neuropathies
Abstract
Military Veterans and active duty personnel are subjected to trauma in their eye structures including the orbit. Research sponsored by the Department of Veterans Affairs (VA) has shown that as many as 75% of Service members who have suffered a traumatic blast injury had visual dysfunction. Often the trauma is not direct but is a consequence of a pressure wave that permeates the entire atmosphere leaving the delicate structures of eyes subjected to excessive damage. The retinal ganglion cells that carry the visual images to the brain suffer damage and either become dysfunctional despite surviving the injury or undergo death due to damage causing glaucoma. Gradual loss of visual function is associated with glaucoma, which will eventually lead to irreversible blindness significantly affecting the functionality and quality of life. Glaucoma is frequently but not always associated with elevation of intraocular pressure (IOP). Current medications are based on IOP-reducing strategies, which helps halt the progression of glaucoma. However, in a number of individuals suffering from glaucoma after traumatic injury, IOP may remain within a normal range (normal tension glaucoma-NTG). NTG also happens to be one of the most recalcitrant types of glaucoma, where IOP reduction may not be effective. The damage and loss of retinal ganglion cells are the real cause of vision loss. Current medications do not address the protection, regeneration, or rehabilitation of these damaged retinal ganglion cells. Our exhaustive studies from the optic nerve and isolated retinal ganglion cells have led us to identify new lipid molecules that show a promise to rehabilitate dysfunctional retinal ganglion cells into a functional state. We propose to determine the effect of these lipids using different mouse models that capture various aspects of this complex disease. Our fundamental approach is to address the rehabilitation as well as regeneration of retinal ganglion cells using select lipids. The proposed research will utilize a mouse model of optic nerve crush and a transgenic mouse model. The optic nerve crush model is similar to blunt or blast-induced trauma to the optic nerve. The transgenic mouse has a defect in a gene that accelerates retinal ganglion dysfunction in the adult phase but not during the development. These models capture different modes of damage to the optic nerve and induce a progressive loss of neurons and progressive loss of vision. About 15% to 25% of current glaucoma patients including military Veterans are recalcitrant to current medications. We propose to evaluate lipids that have shown promise in our initial preliminary studies. In the short term we expect to identify lipids that promote neuro-regeneration in the optic nerve. These studies will also include isolated retinal ganglion cells. In the long term we expect to achieve a combination of lipids/therapeutic molecules that help promote neuro-regeneration and neuro-rehabilitation of the optic nerve results in restoration of lost vision in traumatic optic neuropathies. We expect great benefit to these patients due to the availability of the combination therapy of lipid molecules from our proposed research with existing IOP-lowering agents. The IOP-lowering agents halt further progression but do not restore lost vision. Proposed regenerating lipids may exert wide impact demonstrating restoration of lost vision. This will be of immense benefit to active duty personnel and military Veterans who suffer from glaucoma following traumatic eye injuries. It is expected to benefit the large civilian population suffering from glaucoma as well. The vision loss from trauma occurs in individuals who have an active and productive life. Vision loss affects individuals of all age groups. However, within the age group of patients who lead a very active life, the progressive vision loss incapacitates and especially lowers their quality of life. Regeneration of retinal ganglion cells has the stron
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910845
Entities
People
- Sanjoy K Bhattacharya
Organizations
- United States Army
- University of Miami