Laboratory of Ophthalmic Neurobiology
Research Projects
Primary Open-Angle Glaucoma (POAG) is a chronic neuro-degenerative eye disease
POAG leads to permanent blindness.
Currently there is no cure for Glaucoma.
What do we currently know ?
POAG is a complex disease characterized by progressive and irreversible degeneration of retinal ganglion cells (RGCs) that convey the visual information to the processing centers in the brain.
Elevated Intra-Ocular Pressure (IOP), more than the normal eye can tolerate, associates with the degeneration of RGCs. However, how elevated IOP causes RGC loss is currently unclear.
Ischemia (reduced blood flow in to the central retinal artery) has been implicated in glaucomatous degeneration of RGCs. To investigate whether ischemia promotes the degeneration of RGCs, we have induced ischemia by ligating the optic nerves in mice and found that ischemia, indeed, promotes the degeneration of RGCs through protease- mediated (MMP-9, tPA, and uPA) degradation of ECM protein, laminin (see cartoon the image on the right side).
Excitotoxicity has been implicated in glaucomatous degeneration of RGCs, but the mechanisms are unclear. Prof. Chintala's lab recently reported that excitotoxicity promotes the degeneration of RGCs by up-regulating a novel protein, SARM1.
Until a few years ago, a marker for POAG has not been identified. While working at Vision Research Laboratory at Boston, Prof. Chintala played a key role identifying ELAM-1 as the first known marker for POAG.
Resume
Over 20 years’ experience in academic research.
Over 10 years’ experience in developing animal models for ocular and retinal diseases (Glaucoma, corneal wound healing and angiogenesis).
Over 5 years’ experience in Optical Coherence Tomography (OCT) and live fundus imaging on rodent glaucoma models.
Over 12 years’ experience in developing transgenic and knockout mice.
Over 20 years’ experience in vitro cell and tissue culture models: retinal ganglion cells, glial cells (Muller cells and astrocytes), trabecular meshwork cells, microvascular endothelial cells, three-dimensional neuronal spheroids for high throughput screening, neuronal out growth/ neurite extension assays, tumor cell migration and invasion assays.
Over 15 years’ experience in molecular biology, cell biology, and immunology.
Over 12 years’ experience in developing experimental rodent models for Glioblastoma (brain tumor).
Over 20 years’ experience in microscopy (confocal and traditional fluorescence).
Extensive experience in confocal applications and troubleshooting.
Over 15 years’ experience in training Post-doctoral fellows and undergraduate students.
Successfully obtained grants from National Institutes of Health (NIH) and other sources. Academic appointments
Peer-reviewed Publications:
- Chintala, SK. Tissue and urokinase plasminogen activators instigate the degeneration of retinal ganglion cells in a mouse model of glaucoma. Exp. Eye. Res., 2016, 143, 17-27.
- Chintala, S.K., Cheng, M., and Zhang, X. Decreased expression of DREAM promotes the degeneration of retinal neurons. PLos One, May 28, 2015. DOI: 10.1371/journal.pone.0127776.
- Chintala, S.K., Putris, N., Geno, M. Activation of TLR3 promotes the degeneration of retinal ganglion cells by upregulating the protein levels of JNK3. IOVS, 2015, 56: 505–514.
Massoll, C., Mando, W., and Chintala, SK. Excitotoxicity Up-regulates SARM1 Protein Expression and Promotes Wallerian-like Degeneration of Retinal Ganglion Cells and their Axons. IOVS, 2013, 54:2771–2780.
Mali, RS, Zhang, XM, and Chintala, SK. A decrease in phosphorylation of cAMP-response element-binding protein (CREB) promotes retinal degeneration. Exp. Eye Res., 2011, 92(6):528-36.
Ganesh, SG and Chintala, SK. Inhibition of reactive gliosis attenuates excitotoxicity-mediated death of retinal ganglion cells. PLoS One 2011, 6(3): e18305. doi:10.1371/journal.pone.0018305.
Chintala, S.K., Wang, N., Diskin, S., Mattox, C., Kageman, L., Fini, M.E., and Schuman, J. Matrix Metalloproteinase Gelatinase B (MMP-9) is associated with leaking glaucoma filtering blebs. Exp. Eye Res., 2005,81: 429-436.
Mali, R.S., Cheng, M., and Chintala, S.K. Plasminogen activators promote excitotoxicity-induced retinal degeneration. FASEB J,2005, 19: 1280-1289.
Zhang, X., and Chintala, S.K. Optic nerve ligation leads to astrocyte-associated matrix metalloproteinase-9 induction in the mouse retina. Neuroscience Letters, 2004, 356, 140-144. 8.
Harvey, R, and Chintala, S.K. Inhibition of plasminogen of plasminogen activators attenuates the death of differentiated retinal ganglion cells and stabilizes their neurite network. IOVS, 2007, 48: 1884-1891.
Chintala, S.K. The emerging role of proteases in retinal ganglion cell death. Exp. Eye Res., 2006, 82: 5-12. 15.
Zhang, X., and Chintala, S.K. Influence of interleukin-1 beta induction and mitogen-activated protein kinase phosphorylation on optic nerve ligation-induced matrix metalloproteinase-9 activation in the retina. Exp. Eye Res., 2004, 78 (4), 849-860.
Zhang, X., Cheng, M., and Chintala, S.K. Kainic acid-mediated up-regulation of matrix metalloproteinase-9 promotes retinal degeneration. IOVS, 2004,45: 2374-2383.
Zhang, X., Chaudhry, A., and Chintala, S.K. Inhibition of plasminogen activation protects against ganglion cell loss in a mouse model of optic nerve damage. Molecular Vision, 2003, 9: 238-248.
Wang, N., Chintala, S.K., Fini, M.E., Schuman, J.S. Ultrasound Activates the TM ELAM-1/IL-1/NF-kappaB response: A potential mechanism for intraocular pressure reduction following phacoemulsification. IOVS, 2003,44: 1977-1981.
Chintala, S.K., Zhang, X., Austin, J.F., Fini, M.E. Deficiency in Matrix Metalloproteinase Gelatinase B (MMP-9) Protects against Retinal Ganglion Cell Death after Optic Nerve Ligation. J. Biol. Chem.,2002,277: 47461-47468.
Wang, N., Chintala, S.K*., Fini, M. E., and Schuman, J.S. Activation of a tissue-specific response in the eye’s aqueous outflow pathway defines glaucoma disease phenotype. Nature Medicine, 2001, 7(6): 304-309. * Equal author contribution.
Chintala, S. K., Miller, R.R., and McDevitt, C.A. Role of heparan sulfate in the terminal differentiation of growth plate chondrocytes. Archives of Biochemistry & Biophysics, 1995, 316: 227-234.
Chintala, S. K., Miller, R.R., and McDevitt, C.A. Basic fibroblast growth factor binds to heparan sulfate in the extracellular matrix of rat growth plate chondrocytes. Archives of Biochemistry & Biophysics, 1994, 310: 180-186.
