Poster abstracts

Poster number 87 submitted by Kanika Ghai

The Notch Signaling Pathway influences Neuroprotective and Regenerative Properties of Muller Glia in a Chicken Retina.

Kanika Ghai (Neuroscience, The Ohio State University), Amipratapba Gohil (Neuroscience, The Ohio State University), Andy J. Fischer (Neuroscience, The Ohio State University)

Abstract:
The human retina is composed of light-responsive neurons, and of support cells called Muller glia. These glia have recently been shown to acquire the potential to form mature neurons in damaged retinas of some species (Fischer and Reh, 2001; Ooto et al., 2004). Few studies have determined the mechanisms that regulate the ability of Muller glia to re-enter the cell cycle, become progenitor cells, and differentiate as neurons. Given the similarities between chicken and human retinas, we model retinal degeneration in chickens by injuring their retinas with toxins and study the ensuing glial response. One of the cellular events that is activated in glia following injury is the Notch signaling pathway. This pathway is normally required to suppress neuronal differentiation of progenitors during development of the retina in various species (Dorsky et al., 1997; Henrique et al., 1997). Further, notch1 and hes1 have been shown to influence the differentiation of Muller glia during late stages of rat retinal development (Furukawa et al., 2000). Beyond this, the role of this pathway in the postnatal retina is unknown.
Here we show that components of the Notch signaling pathway are expressed in Muller glia even at baseline levels in an undamaged retina. Further, this expression of Notch-1 and its downstream effectors are upregulated in a damaged retina and also in an undamaged retina in the presence of the growth factors insulin and FGF2. When we block Notch activity prior to retinal damage using DAPT, a gamma-secretase inhibitor, we observe that Notch-mediated signaling can have varied effects on NMDA-induced excitotoxic cell death in the retina, depending on the dose of NMDA used. Taken together, our data provides new insights into the role of the Notch signaling pathway in regulating neuroprotective functions of Muller glia prior to retinal damage and their regenerative functions in a damaged retina.

References:
1) Fischer AJ, Reh TA. Nat Neurosci. 2001 Mar;4(3):247-52.
2) Ooto S, Akagi T, Kageyama R, Akita J, Mandai M, Honda Y, Takahashi M.
Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13654-9.
3) Dorsky RI, Chang WS, Rapaport DH, Harris WA. Nature 1997 Jan 2;385(6611):67-70.
4) Henrique D, Hirsinger E, Adam J, Le Roux I, Pourquié O, Ish-Horowicz D, Lewis J. Curr Biol. 1997 Sep 1;7(9):661-70.
5) Furukawa T, Mukherjee S, Bao ZZ, Morrow EM, Cepko CL. Neuron. 2000 May;26(2):383-94.

Keywords: Notch, Retina, DAPT