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Research

Glaucoma, the leading cause of blindness by neurodegeneration, is an age-dependent retinal and optic nerve disease. Glaucoma is prevalent in the aged, is often associated with ocular hypertension, and currently affects 100 million people worldwide. The affected neurons, the retinal ganglion cells (RGCs), lose their axon structural and functional integrity, synaptic connectivity, and ultimately die by apoptosis of their soma. The converging triggers for this compartmentalized and progressive optic neurodegeneration, and the multiple specific molecular pathways and cell interactions that partake in the slow RGC demise remain unclear. RGCs interact with diverse nonneuronal cells within the retina, optic nerve and brain, such as astrocytes, Muller cells, oligodendrocytes and microglia, which may signal their dysfunction and degeneration. While microglia overactivation and deregulation are common to aging and multiple
neurodegenerative disorders, the link of retinal microglia with glaucoma remains underexplored.

Modeling glaucoma in a mouse strain that develops the disease with hallmarks mimicking human glaucoma, we are studying the earliest pathological changes affecting their retinas. We aim at determining the role of microglia activation on the pathological synapse elimination and axonal degradation preceding RGC dysfunction and death. Understanding the contribution of microglia to the pathophysiology of glaucoma may provide us with a novel tool or targets to prevent irreversible vision loss, and may uncover means to diagnose the disease at its onset.

Selected Publications

Search Pubmed for Alejandra Bosco's publications

Bosco A., Inman D.M., Steele M.R., Wu G., Marsh-Armstrong N., Calkins D., Horner P.J., Vetter
M.L. (2008). Minocycline reduces retinal microglial activation and improves optic nerve integrity
in the DBA/2J mouse model of glaucoma. Investigative Ophthalmology and Vision Science,
49:1437-46.

Bosco A., Cusato K., Nicchia G.P., Frigeri A., Spray D.C. (2005). A developmental switch in the
expression of aquaporin-4 and Kir4.1 from horizontal to Muller cells in mouse retina.
Investigative Ophthalmology and Vision Science 46:3869-75.

Cusato K., Bosco A., Rozental R., Guimarães C.A., Reese B.E., Linden R., Spray D.C. (2003). Gap
junctions mediate bystander cell death in developing retina. Journal of Neuroscience 23: 6413-
22.

Cusato K., Bosco A., Linden R., Reese B.E. (2002). Cell death in the inner nuclear layer of the
retina is modulated by BDNF. Developmental Brain Research 139:325-30.

Bosco A., Linden R. (1999). BDNF and NT-4 differentially modulate neurite outgrowth and
pattern in developing retinal ganglion cells. Journal of Neuroscience Research 57:759-69.

Textbooks and Chapters

• Nicchia G.P., Nico B., Camassa L.M.A., Mola M.G., Ribatti D., Spray D.C., Bosco A., Svelto M.,
  Frigeri A. Responsive astrocytic endfeet: the role of AQP4 in BBB development and functioning.
  Blood-Brain Barriers. From ontogeny to artificial interfaces Eds. Rolf Dermietzel, David C. Spray
  and Maiken Nedergaard. Weinheim, Wiley, 2006.