National Glaucoma Research
David J. Calkins, Ph.D.
Vanderbilt University Medical Center
Nashville, TN, United States
Title: Mapping the Protein and Lipid Signature of Glaucoma
Non-Technical Title: Molecular Changes Underlying Vision Loss in Glaucoma
Kevin Schey, Ph.D.
Duration: July 1, 2011 - June 30, 2013
Award Type: Standard
Award Amount: $100,000
Vision loss in glaucoma involves death of the optic nerve through unknown changes in the composition of the retina and nerve. Our studies will measure how elevated pressure in the eye causes compositional changes in the retina and optic nerve by imaging specific groups of molecules in intact tissue. This will help us identify new targets for potential treatments.
Aging and elevated eye pressure both contribute to vision loss in glaucoma by changing the activity of proteins and fats in the eye. Drs. David John Calkins, Kevin Schey, and collaborators have previously developed an inducible glaucoma mouse model that was funded in part through a previous BrightFocus grant. In this model, tiny Styrofoam beads are injected into mouse eyes to block the flow of a liquid called the aqueous humor, causing an increase in eye pressure that then damages the optic nerve and leads to glaucoma. The researchers will use a special kind of detection laser and camera (called MALDI mass spectrometry imaging) to create a “road map” of the protein and fat changes in the retina and brain. By giving these mice glaucoma at various ages, this approach will separate age‐dependent from eye‐pressure‐dependent changes. The results will give clues for future treatments for glaucoma and perhaps for other eye or brain diseases associated with aging, like Alzheimer's disease or macular degeneration.
Anderson, D.M.G., Mills, D. Spraggins, J., Lambert, W.S., Calkins, D.J., Schey, K.L. (2013) High-resolution matrix-assisted laser desorption ionization-imaging mass spectrometry of lipids in rodent optic nerve tissue. Molecular Vision, 19:581-592
Aging and elevated eye pressure both contribute to vision loss in glaucoma by changing the activity of protein and fat (lipid) molecules in the retina and optic nerve at the back of the eye. Dr. Calkins’ team has previously developed an inducible glaucoma mouse model that was funded in part through a previous AHAF grant. In this model, tiny beads are injected into mouse eyes to block the flow of a liquid called the aqueous humor, causing an increase in eye pressure that then damages the optic nerve and retina and leads to glaucoma. For comparison, they are also using a type of mouse called DBA/2J that has naturally-occurring glaucoma so that they can compare their findings across different experimental systems.
This past year, Dr. Calkins’ group used a special kind of detection laser and camera (called MALDI mass spectrometry imaging) to begin to create a "road map" of the protein and lipid changes in the retina and optic nerve. Because many changes in proteins and lipids reflect the energy demands of the retina and optic nerve as the disease progresses, they also developed a MALDI imaging procedure to map changes in the major source of energy for all tissues: a molecule called ATP. The team has found in this first year several lipids associated with early degeneration in glaucoma. The changes in these lipids in both the retina and optic nerve of both models were not uniform. Rather, each distributed in pockets of activity that resemble the pockets of vision loss in glaucoma. Similarly, early changes in ATP also followed a patchy distribution. Thus, Dr. Calkins’ team believes that these findings may provide a clue to the underlying molecular changes that happen before the loss of vision in glaucoma.
Dr. Calkins is the Vice-Chairman and Director for Research of the Vanderbilt Eye Institute at the Vanderbilt University Medical Center in Nashville, TN. He has been faculty in neuroscience there since 2004. Previously, he was faculty at the University of Rochester Center for Visual Sciences. Dr. Calkins' laboratory takes an integrative approach to understanding the mechanisms of neurodegeneration in blinding eye diseases, with a focus on glaucoma. Through this research, Dr. Calkins hopes to identify novel therapeutic targets and test their potential in preventing vision loss. In addition to his BrightFocus award, Dr. Calkins is the recipient of multiple NIH and industry grants.