Molecular Changes Underlying Vision Loss in Glaucoma

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.