The Role of Axonal Transport in Glaucoma

Abstract

Glaucoma is a neurodegenerative disease that affects the retinal ganglion cells (RGCs) and leads to progressive vision loss. The first pathological signs can be seen at the optic nerve head (ONH), the structure where RGC axons leave the retina to compose the optic nerve. Besides damage of the axonal cytoskeleton, axonal transport deficits at the ONH have been described as an important feature of glaucoma. Axonal transport is essential for proper neuronal function, including transport of organelles, synaptic components, vesicles, and neurotrophic factors. Impairment of axonal transport has been related to several neurodegenerative conditions. Studies on axonal transport in glaucoma include analysis in different animal models and in humans, and indicate that its failure happens mainly in the ONH and early in disease progression, preceding axonal and somal degeneration. Thus, a better understanding of the role of axonal transport in glaucoma is not only pivotal to decipher disease mechanisms but could also enable early therapies that might prevent irreversible neuronal damage at an early time point. In this review we present the current evidence of axonal transport impairment in glaucomatous neurodegeneration and summarize the methods employed to evaluate transport in this disease.

Keywords: axonal transport; glaucoma; neurodegeneration; optic nerve head.

Figure 1

Axonal transport impairment and RGC degeneration in glaucoma. (a) Physiological condition, in which axonal transport integrity guarantees the exchange of several molecules, vesicles and organelles throughout the axon, important to maintain RGC function. (b) Axonopathy in glaucoma. Here, axonal transport impairment is an early event in disease progression, leading to accumulation of several components in the ONH, that would normally be transported along the axon (1). Alterations in axonal transport are associated with alterations of the cytoskeleton, preceding axonal degeneration (2) and ultimately, apoptosis of RGC cell bodies in the retina (3). Abbreviations: RGC = retinal ganglion cells; ONH = optic nerve head; IOP = intraocular pressure; OPP = ocular perfusion pressure.