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This abstract is assigned to session Poster session in O'Bistro

Title

Glaucoma from eye to brain: are matrix metalloproteinases (MMPs) involved?

Purpose	MMPs are often linked to glaucoma, however a clear definition of their role is lacking. Moreover, glaucoma is increasingly recognized as a disorder of ‘visual neurons’ within the eye and brain. Unraveling the influence of glaucoma on the visual system circuitry, and the role of MMPs herein, will help to better understand glaucoma. Here, we report on (1) the pathological changes of the visual system; and (2) the involvement of MMPs, during glaucoma.
Methods	As an in vivo mouse model of glaucoma, we used intravitreal NMDA injections to induce apoptosis of retinal ganglion cells (RGCs). The impact on the retina and its target areas was examined via immunohistochemical stainings (IHC). Alterations in MMP expression/activity were assessed via IHC and zymography.
Results	Excitotoxic RGC death induces loss of neurons and synaptic connections in the retinal target areas and is accompanied by extensive glial reactivity. In the healthy retina, MMP-2, -3, and -14 are expressed by Müller glia. Strong MMP-14 expression is also found in RGC axons in the nerve fiber layer, the optic nerve and the primary visual brain targets. Whereas MMP-9 is not detectable in de healthy retina, its expression increases in RGCs as they undergo apoptosis. However, the most upregulated MMP in excitotoxic versus healthy retinas, is MMP-3.
Conclusion	Based on their expression patterns, we hypothesize that MMPs are involved in RGC death and glial reactivity in the retina. Therefore, we are currently investigating their in vivo role in specific MMP deficient mice subjected to the excitotoxicity model. Moreover, the glaucomatous changes observed in the brain indicate that these retinal target areas should not be overlooked in future research.

Authors 1

Last name	DE GROEF
Initials	L
Department	KU Leuven
City	Leuven

Authors 2

Last name	Dekeyster
Initials	E
Department	KU Leuven
City	Leuven

Authors 3

Last name	Gaublomme
Initials	D
Department	KU Leuven
City	Leuven

Authors 4

Last name	Moons
Initials	L
Department	KU Leuven
City	Leuven