Abstract
Purpose: :
To test the hypothesis that glial cells provide neuroprotection, we are visualizing the metabolic response of Müller glial cells to photoreceptor degeneration.
Methods: :
Visualizing and quantifying the metabolic states of activated glia is possible through the integration of high resolution, N-dimensional metabolic profiling (Computational Molecular Phenotyping, CMP), electron microscopy, classic glial proteome profiling, and proliferation assays. We are using the classic light-induced retinal damage model in albino mice to characterize the glial response to photoreceptor degeneration.
Results: :
CMP is capable of visualizing thousands of Müller cells and photoreceptors covering large stretches of retina while resolving the metabolic response of individual Müller cells and photoreceptors, preserving all histological context. We found that glial processes surrounding stressed photoreceptors exhibit changes in metabolic envelopes, displaying altered metabolic signals for glutamate metabolism, osmoregulation, anti-oxidation and retinoid metabolism. These metabolic profiles may reveal altered metabolic stabilities, altered metabolic programming or biochemical response profiles indicative of cell stress.
Conclusions: :
This work is aimed at investigating the metabolic relationships between Müller cells and photoreceptors in retinal stress situations. Metabolic networks are likely complex and we propose that the metabolic response of activated Müller cells assists metabolically stressed or challenged photoreceptors. The power of CMP to integrate various levels of cell regulation (metabolism, energetics and proteomics) with high spatial resolution is paving the way to discover the molecular glial transformations that confer neuroprotection.
Keywords: degenerations/dystrophies • Muller cells • metabolism