Morphology, but not microtubules, of the retinal nerve fibers are protected by nicotinamide in glaucoma mice
Glaucoma is a blinding disease where the retinal ganglion cells (RGCs) and the axons degenerate. Degradation of axonal microtubules is thought to play a critical role in the pathogenesis, but the mechanism is unknown. Here we investigate whether microtubule disruption in glaucoma can be alleviated by metabolic rescue. Using nicotinamide to reduce metabolic stress, the morphology and integrity of microtubules of the retinal nerve fibers are examined in a mouse model of glaucoma, DBA/2. Surprisingly, we found that morphology but not microtubules are protected by the dietary supplement of nicotinamide. Co-registered second-harmonic generation and immunofluorescence images shows that microtubule deficit is not due to a shortage of tubulins and colocalizes with the sectors in which RGCs are disconnected from the brain, indicating that the instability of axonal microtubules may underlie axonal transport deficit in glaucoma. Together, our data confirms distinct roles of axonal microtubules in glaucomatous degeneration, offering a new opportunity for neuroprotection.