Friday, May 9, 2025
5/9/2025
Novel growth factors and regenerative RGC subtypes for optic nerve regeneration - Project Abstract or Summary Following injury to the optic nerve in mammals, retinal ganglion cells (RGCs) cannot regenerate their axons and soon undergo apoptotic cell death, leading to permanent vision loss. Some degree of optic nerve regeneration can be induced experimentally but the extent of regeneration achieved to date remains away from the level of visual functional recovery required, pointing to the need for more effective therapies. Aside from testing well established growth factors and chance discoveries of several novel factors, a more systematic screening of as yet untested ligands to the many trophic factor and chemokine receptors that are expressed in adult RGCs could augment regeneration well beyond currently achievable levels. In recent genetic studies (RNA-Seq, FACS- purified cells), we have obtained an extensive list of growth factor, chemokine and peptide receptors that are expressed in adult RGCs, many of whose ligands have not been tested for effects on axon regeneration and RGC protection. To carry out the screening, we will use an adult RGC culture system and in vivo optic nerve regeneration models that have been used on our lab for 2 decades, and which have enabled us identify three previously unknown potent factors for optic nerve regeneration. The proposed studies will screen the ligands to the multiple receptors that are expressed in adult RGCs to discover novel factors for optic nerve regeneration and RGC survival. With significantly improved automated cell culture system, Aim 1 will carry out an in vitro bioactivity screen and verify hits in vivo, respectively. Aim 2 will screen which subtypes of RGCs are responding to the known effective treatments and the new hits from Aim 1. This will enable us develop combinatorial treatments to stimulate axon regeneration from multiple RGC subtypes simultaneously. Through these studies, we expect to promote considerably greater levels of axon growth than can be attained currently and ultimately bring us closer to improving visual function after optic nerve damage.
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