Primary Open-Angle Glaucoma (POAG) leads to permanant blindness and affects more than 60 million people worldwide. POAG is a complex neurodegenerative disease characterized by progressive and irreversible loss (death) of retinal ganglion cells (RGCs) that convey visual information recieved by photoreceptors cells (rods and cones) to the processing centers in the brain.
Although it is unclear how RGCs die under glaucomatous conditions, a number of investigators documented that elevated Intra-Ocular Pressure (IOP) (more than the normal eye can tolerate) associates with RGC loss in glaucoma. Yet, how elevated IOP causes RGC loss is unclear.
Prof. Chintala's laboratory has been attempeting to find out whether elevated IOP can increase levels of certain proteases (that degrade the native enironment to which RGCs attach to), and increased levels of the proteases then cause the death of RGCs. During the past ten years of research, Prof. Cinthala found that elevated IOP indeed increaes levels of three proteases Matrix MetalloProtienase-9 (MMP-9, tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA). Prof. Chintala also found that the proteases, indeed, degrade the extracellular matrix (ECM) within the ganglion cell layer and promote the loss of RGCs. The long-term goal of Prof. Chintala is to develop pharmacological agents (that inhibit the synthesis or decrease protease activity of MMP-9, tPA, and uPA) to prevent RGC loss in glaucoma.
Recent studies from Prof. Chintala's laboratory indicate that excitotoxicity up-regulates SARM1 protein, exclusively in RGCs, and promotes Wallerian-like degeneration of RGCs and their axons. For details, go to this link: http://www.iovs.org/content/early/2013/03/20/iovs.12-10973.abstract