Our objective is to identify new molecular targets for early detection and treatment of glaucoma. During the progression of glaucoma, the axons of the retinal ganglion cells (RGCs) are gradually lost. Our hypothesis is that axonal microtubules (MTs) are critically involved in the process. We demonstrated recently, using second- harmonic generation (SHG) microscopy as a novel retinal imaging and DBA mice as a model of inherited glaucoma, that axonal MTs degrade more rapidly than the loss of RGC axons (‘MT deficit’) and MT deficit is spatially correlated with axonal atrophy. Our results suggest that MT deficit is a new pathology of early glaucoma, which may have a common pathogenic origin as the loss of RGC axons. Here we aim to explore the capacities of newly discovered pathology beyond early detection. We hypothesize that MT deficit may represent a reversible stage suitable for therapeutic intervention and provide the molecular substrate for the RGC’s sensitivity to the elevated IOP triggering the pathological response. To test this notion, the mechanism of MT deficit must be elucidated. As a potential target, we will interrogate the posttranslational modifications (PTMs) of axonal MTs, also known as the tubulin codes, which modulate the interaction between MTs and MT-associated proteins (MAPs). Our research will show how MT PTMs are altered during glaucoma and whether the change is correlated with MT deficit. Also, we will test MT deficit as an endpoint marker of the RGC viability evaluating the efficacy of therapeutic treatments. We will analyze the DBA retina receiving an increased level of NAD+ to protect the RGC axons. Our research can yield valuable insights into the mechanism of MT deficit and open a new line of questions toward improved glaucoma therapy.