| First Author | Fu CT | Year | 2012 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 53 |
| Issue | 1 | Pages | 76-84 |
| PubMed ID | 22064993 | Mgi Jnum | J:191389 |
| Mgi Id | MGI:5461626 | Doi | 10.1167/iovs.11-8546 |
| Citation | Fu CT, et al. (2012) Involvement of EphB/Ephrin-B signaling in axonal survival in mouse experimental glaucoma. Invest Ophthalmol Vis Sci 53(1):76-84 |
| abstractText | PURPOSE: To examine the functional significance of EphB/ephrin-B upregulation in mouse experimental glaucoma. METHODS: In a loss-of-function approach, mouse mutants lacking EphB2 (EphB2(-/-)) or EphB3 (EphB3(-/-)) protein, and mutants expressing EphB2 truncated in the C-terminus (EphB2(lacZ/lacZ)) were subjected to laser-induced ocular hypertension (LIOH), an experimental mouse model of glaucoma. The number of optic nerve axons was counted in paraphenylenediamine (PPD)-stained sections and compared between EphB mutants and wild type littermates. In a gain-of-function approach, retina/optic nerve explants obtained from LIOH-treated animals were exposed to EphB2-Fc recombinant proteins or Fc control proteins. Tissue sections through the optic nerve head (ONH) were labeled with neuron-specific anti-tubulin beta-III antibody to determine axonal integrity. RESULTS: Both EphB2 and EphB3 null mutant mice exhibited more severe axonal degeneration than wild type littermates after treatment with LIOH. Mutant mice in which the C-terminal portion of EphB2 is truncated had an intermediate phenotype. Application of EphB2-Fc recombinant protein to LIOH-treated optic nerve explants resulted in greater sparing of tubulin beta-III-containing retinal ganglion cell (RGC) axons. CONCLUSIONS: These results provide genetic evidence in mice that both EphB/ephrin-B forward and reverse signaling feed into an endogenous pathway to moderate the effects of glaucomatous insult on RGC axons. LIOH-induced axon loss is maintained in retina/optic nerve explants after removal from an ocular hypertensive environment. Exogenous application of EphB2 protein enhances RGC axon survival in explants, suggesting that modulation of Eph/ephrin signaling may be of therapeutic interest. |
