Assessing Metabolic Changes in the Retina & Optic Nerve During Glaucoma




Journal Title

Journal ISSN

Volume Title



Purpose: Glaucoma is an optic neuropathy characterized by retinal ganglion cell (RGC) death and optic nerve degeneration. Glial cells such as astrocytes form a metabolic unit with neurons to exchange metabolic substrates and neurotransmitters. When exposed to ocular hypertension (OHT), this metabolic unit is disrupted as astrocytes undergo morphological changes in response to increased pressure. ONHAs also reduce their GLUT1 expression, further exacerbating their metabolic function. It is unknown how these changes impact RGC axon structure and function, so we aim to gain insight into the metabolic relationship between glia and neurons during glaucoma. We hypothesize that glaucoma induces metabolic strain in optic nerve head astrocytes (ONHAs), preventing the exchange of metabolites between neurons, ultimately causing a decline in RGC structure and function. Methods: We have taken a two-sided approach to studying these neural-glial interactions. First, we have induced OHT as well as glucose transport inhibition in ONHAs in vivo to examine the effect of pressure-induced stress on metabolism and the visual system. Currently, we are working in vitro to study the metabolic exchange between RGCs and ONHAs co-cultured in microfluidic chambers when the ONHAs are exposed to biaxial strain as well as GLUT1 KO. Results: Preliminary results in vivo have shown that OHT and glucose transport inhibition in ONHAs disrupt anterograde transport. However, RGCs can compensate for glucose transport inhibition in astrocytes by upregulating GLUT3 and MCT2.In vitro we expect to see RGCs respond to alterations in ONHA metabolism, similarly, upregulating their lactate transporters and relying on mitochondrial metabolism to maintain their energetic needs. Conclusion: Using this model will allow us to directly observe the metabolic changes in the neural-glial unit induced by glaucoma, ultimately providing us insight into targets for future glaucoma therapies.