Glaucoma is one of the leading causes of blindness in the Veterans population, estimated to affect 285,000 American Veterans as well as 60 million people worldwide, and is the most common neurodegenerative disease. The exact mechanism by which vision loss occurs in glaucoma is not fully understood, which hinders development of a true cure for this disease. It is thought that excessive deformation of the optic nerve tissues in the posterior eye under the insult of elevated intraocular pressure leads to an unfavorable biomechanical environment for cells of the optic nerve head. These cells include the retinal ganglion cells, whose axons transmit visual information from photoreceptors to the brain. Based upon an increasing body of evidence suggesting that the stiffness of the sclera (the white outer coat of the eye) may greatly influence the degree of deformation of the posterior eye, we hypothesize that stiffening the peripapillary sclera will protect against vision loss in glaucoma. Whereas current therapies only delay the onset of symptoms, stiffening the peripapillary sclera could be a novel treatment for glaucoma. In this study, our approach is to screen the efficacy of potential chemical agents and engineered viral vector approaches that modulate peripapillary scleral stiffness in a rat model of glaucoma. In the first specific aim, we will use an optical tracking technique called digital image correlation to quantitatively assess the magnitude of stiffening these agents have on rat scleras. We will also develop a surgical technique to deliver these agents to the back of the eye under ultrasound guidance without affecting surrounding structures. Once we determine the most effective agents, in the second specific aim, we will deliver these agents to rats with surgically-induced glaucoma. Our experimental paradigm is a 3x2 study, where we will compare rats with and without induction of glaucoma to rats with and without delivery of peripapillary scleral stiffening agents (plus additional sham controls). Over 8 weeks, we will monitor anatomic changes to the eye and quantify the degree of vision loss by measuring the rats' visual acuity and contrast sensitivity. At the conclusion of the experiment, we will analyze the expression of genes and proteins associated with glaucoma and ocular damage to determine the overall health of the eyes. The expected outcome of this study is that rats with stiffened peripapillary scleras will experience less vision loss under glaucomatous conditions than glaucomatous rats with no peripapillary scleral stiffening. This will provide the first in vivo data regarding the efficacy of this novel approach to treating glaucoma. If successful, these findings will motivate development of a human clinical trial to deliver biocompatible stiffening agents to prevent vision loss in glaucoma. Overall, the motivation for this study is the need for a better understanding of ocular biomechanics towards the long-term goal of developing a cure for glaucoma in clinical use for Veterans and others with this disease. This meets the Rehabilitation Research and Development goal of preventing and treating vision loss. This project represents a method to screen potential glaucoma treatments in an animal model, as well as to train the postdoctoral candidate to become a successful and productive independent investigator in the field of ocular biomechanics within the VA research environment.
Glaucoma is the second leading cause of blindness worldwide and is a major cause of vision loss for veterans, as risk for glaucoma increases steadily with age. Unfortunately, although treatments exist, these typically delay the onset of symptoms and are not a true cure. By better understanding how mechanical deformation of the posterior eye leads to vision loss, we seek to design and test a novel treatment paradigm to prevent vision loss in glaucoma. This treatment could complement existing therapies in order to further delay or prevent entirely any vision loss in veterans at risk for glaucoma. If successful in rats, this treatment approach could motivate development of a human clinical trial to preserve vision in veterans with glaucoma.
| Campbell, Ian C; Hannon, Bailey G; Read, A Thomas et al. (2017) Quantification of the efficacy of collagen cross-linking agents to induce stiffening of rat sclera. J R Soc Interface 14: |
| Coudrillier, Baptiste; Campbell, Ian C; Read, A Thomas et al. (2016) Effects of Peripapillary Scleral Stiffening on the Deformation of the Lamina Cribrosa. Invest Ophthalmol Vis Sci 57:2666-77 |
| Coudrillier, Baptiste; Geraldes, Diogo M; Vo, Nghia T et al. (2016) Phase-Contrast Micro-Computed Tomography Measurements of the Intraocular Pressure-Induced Deformation of the Porcine Lamina Cribrosa. IEEE Trans Med Imaging 35:988-99 |
| Campbell, Ian C; Coudrillier, Baptiste; Mensah, Johanne et al. (2015) Automated segmentation of the lamina cribrosa using Frangi's filter: a novel approach for rapid identification of tissue volume fraction and beam orientation in a trabeculated structure in the eye. J R Soc Interface 12:20141009 |
