Abstract

Glaucoma is a family of diseases characterized by degenerative optic neuropathy usually related to elevation of lOP and retinal ganglion cells loss. Despite recent advances in identifying genes related to glaucoma our understanding of the pathophysiology of the disease is still limited. The long-term objective of this project is to determine the molecular mechanisms leading to the development of retinal pathology in glaucoma. To achieve this goal, differential gene expression in whole retina of mice (both glaucomatous and non-glaucomatous) of various ages (from 3 to 18 months of age) will be determined using microarray gene analysis. In addition, differential gene expression among areas of the retina with various degrees of RGC loss in aged glaucomatous animals (15 to 18 months of age) will be determined using the same methodology. Retinal gene expression will also be correlated to the lOP exposure history in glaucomatous animals. All microarray analysis results will be confirmed at the RNA as well as the protein level. Through preliminary experiments, a number of genes whose expression changes with the progression of glaucomatous retinal pathology have already been identified. This project will also investigate whether changes in expression of two of these genes, ceruloplasmin (cp) and complement component 1q (C1q), have a beneficial/protective or detrimental/destructive role in glaucoma. This will be achieved by generating congenic animals in the DBA/2 glaucomatous background that carry knockout mutations in these two genes. The up-regulation in the level of expression of the cp and C1q proteins will also be confirmed in archival tissue material from experimental primate glaucoma and patients with glaucoma by immunohistochemistry. Completion of this project will increase our understanding of the molecular pathways within the retina involved in the pathogenesis of glaucoma and might allow the identification of novel targets for development of new therapeutic approaches.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY015224-04
Application #
7279833
Study Section
Special Emphasis Panel (ZRG1-AED (01))
Program Officer
Liberman, Ellen S
Project Start
2004-09-06
Project End
2009-08-31
Budget Start
2007-09-01
Budget End
2009-08-31
Support Year
4
Fiscal Year
2007
Total Cost
$411,475
Indirect Cost

  Institution

Name
Mount Sinai School of Medicine
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029

  Publications

Polla, Daniel; Astafurov, Konstantin; Hawy, Eman et al. (2017) A Pilot Study to Evaluate the Oral Microbiome and Dental Health in Primary Open-Angle Glaucoma. J Glaucoma 26:320-327
Scalia, Frank; Rasweiler 4th, John J; Danias, John (2015) Retinal projections in the short-tailed fruit bat, Carollia perspicillata, as studied using the axonal transport of cholera toxin B subunit: Comparison with mouse. J Comp Neurol 523:1756-91
Kumari, Ruma; Astafurov, Konstantin; Genis, Alina et al. (2015) Differential Effects of C1qa Ablation on Glaucomatous Damage in Two Sexes in DBA/2NNia Mice. PLoS One 10:e0142199
Astafurov, Konstantin; Dong, Cecilia Q; Panagis, Lampros et al. (2014) Complement expression in the retina is not influenced by short-term pressure elevation. Mol Vis 20:140-52
Astafurov, Konstantin; Elhawy, Eman; Ren, Lizhen et al. (2014) Oral microbiome link to neurodegeneration in glaucoma. PLoS One 9:e104416
Lim, Hyungsik; Danias, John (2012) Label-free morphometry of retinal nerve fiber bundles by second-harmonic-generation microscopy. Opt Lett 37:2316-8
Elhawy, Eman; Kamthan, Gautam; Dong, Cecilia Q et al. (2012) Pseudoexfoliation syndrome, a systemic disorder with ocular manifestations. Hum Genomics 6:22
Lim, Hyungsik; Danias, John (2012) Effect of axonal micro-tubules on the morphology of retinal nerve fibers studied by second-harmonic generation. J Biomed Opt 17:110502
Panagis, Lambros; Zhao, Xiujun; Ge, Yongchao et al. (2011) Retinal gene expression changes related to IOP exposure and axonal loss in DBA/2J mice. Invest Ophthalmol Vis Sci 52:7807-16
Blitzer, Andrea L; Panagis, Lampros; Gusella, G Luca et al. (2011) Primary cilia dynamics instruct tissue patterning and repair of corneal endothelium. Proc Natl Acad Sci U S A 108:2819-24

Showing the most recent 10 out of 21 publications