The role of glia in inner retinal changes during retinal degeneration
Development of treatments that provide novel ways of replacing photoreceptors (e.g.bionic eye, stem cells, or optogenetic gene therapies) assumes that the inner retina remains intact, and that ganglion cells (the output neurons of the retina) remain capable of passing any light signals to higher cortical areas. However, pre-clinical models of retinal degeneration and Retinitis Pigmentosa patients show significant alterations and plastic neuronal changes in the inner retina.
We have developed a pre-clinical model that allows us to detect functional changes in the inner retina. Our data show that retinal ganglion cells undergo a series of changes well after the loss of photoreceptors and that their dysfunction and death is linked to altered retinal glial cell function.
In this project we will test whether ganglion cells become dysfunctional and die because of altered glial function late in retinal degeneration. We will firstly examine the functional and morphological changes in retinal ganglion cells in pre-clinical models. Secondly, we will evaluate the role of proliferative gliosis in creating these ganglion cell changes. Finally, we will evaluate whether prevention of glial proliferation ameliorates the inner retinal plastic changes and in particular preserves ganglion cell number and function. The information generated from this project is crucial for the optimal development of technologies like electronic retinal implants (bionic eye). In addition, the knowledge gained about the role of gliosis in neuronal dysfunction and death is applicable to other neurodegenerative diseases.
Figure 1: Inner retinal ganglion cells are altered after photoreceptor degeneration.
Retinal ganglion cells showing bending of axons (A) and curled dendrites (B) well after photoreceptor loss. A 3D reconstruction of a ganglion cell showing altered morphology.
Dr Ursula Greferath, Senior Research Officer
Faculty Research Themes
School Research Themes
For further information about this research, please contact the research group leader.