Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


osu1256322124.pdf (5.99 MB)

ETD Abstract Container

Abstract Header

Notch-Signaling in Retinal Regeneration and Müller glial Plasticity

Ghai, Kanika
http://rave.ohiolink.edu/etdc/view?acc_num=osu1256322124

Abstract Details

2009, Doctor of Philosophy, Ohio State University, Neuroscience.
Eye diseases such as blindness, age-related macular degeneration (AMD) and glaucoma are highly prevalent in a rapidly aging population. These sight-threatening diseases all involve the progressive loss of cells from the retina, light-sensing neural tissue in the eye. Thus, developing strategies to replace dying retinal cells or prolonging neuronal survival is essential to preserving sight. This dissertation elucidates the properties of the primary support cell in the chicken retina, known as the Müller glia, which have been shown to possess stem-cell like properties, with the potential to form new neurons in damaged retinas. However, the mechanisms that govern this stem-cell like ability are less well understood. Here, we analyze the role of one of the key developmental processes, i.e., the Notch-Signaling Pathway in regulating proliferative, neuroprotective and regenerative properties of Müller glia that bestow them with this plasticity. The first part of this dissertation, we find that inhibition of γ-secretase activity associated with Notch-signaling and silencing of the bHLH effectors Hes1 and Hes5 have distinctly different outcomes on cell-fate specification of cultured chicken retinal progenitors. Further, our studies reveal that Notch-signaling plays a limited but important role during retinal regeneration. Components of the Notch-signaling pathways are transiently upregulated in proliferating Müller glia after damage in a chicken retina and blocking Notch after damage enhances some neural regeneration from glial-derived progenitors. In the second part of this dissertation, we analyze the role of the Notch pathway in the postnatal retina in the absence of damage. We find that components of the Notch-signaling pathway are expressed at low levels in most Müller glia in undamaged retina. Further, Notch-signaling influences the phenotype and function of Müller glia in the mature retina; low levels of Notch-signaling diminish the neuroprotective capacity of Müller glia, but are required to maintain their ability to become progenitor-like cells. We also find that there is cross-talk between Notch and MAPK pathways – FGF2, a secreted protein that activates the MAPK pathway, also induces the expression of Notch pathway genes. Our data indicate that Notch-signaling is down-stream of and is required for FGF2/MAPK- signaling to drive the proliferation of Müller glia. The last part of this dissertation describes the patterning of the immature zone of cells present at the retinal margin, called the circumferential marginal zone (CMZ). Additionally, we describe the morphological and mechanistic properties of a unique subset of interneurons we discovered in the retina, called the serotonin-accumulating bipolar cells. Our data indicates that these cells perform glial functions by actively transporting and degrading serotonin that is synthesized in neighboring amacrine cells. Taken together, the data presented in this dissertation furthers understanding of Müller glial plasticity. This information could be applied to stimulating neural regeneration, harnessing Müller glia as a localized source of stem cells, developing therapies targeted to glia and countering neuronal death in eye diseases. Additionally, our studies on serotonin-accumulating bipolar cells have implications for understanding the mechanisms of melatonin biosynthesis and retinal circadian rhythms, dysfunctions of which lead to photoreceptor degeneration and loss of vision.
Dr. Andy Fischer, PhD (Committee Chair)
Heithem El-Hodiri, PhD (Committee Member)
Susan Cole, PhD (Committee Member)
Paul Henion, PhD (Committee Member)
202 p.
Biology; Molecular Biology; Ophthalmology
retina; M&252; ller glia; plasticity; regeneration; serotonin; bipolar cells; CMZ; proliferation; cell death

Recommended Citations

Citations

  • Ghai, K. (2009). Notch-Signaling in Retinal Regeneration and Müller glial Plasticity [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1256322124

    APA Style (7th edition)

  • Ghai, Kanika. Notch-Signaling in Retinal Regeneration and Müller glial Plasticity. 2009. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1256322124.

    MLA Style (8th edition)

  • Ghai, Kanika. "Notch-Signaling in Retinal Regeneration and Müller glial Plasticity." Doctoral dissertation, Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1256322124

    Chicago Manual of Style (17th edition)

osu1256322124
2,320
© 2009, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.