Anatomical and Molecular Responses Triggered in the Retina by Axonal Injury

After receiving their visual input from photoreceptors via the intermediate neurons (bipolar, horizontal and amacrine cells), retinal ganglion cells (RGCs) relay this intraretinally preprocessed visual information to the centres in the brain for further processing. Thus, RGCs are the only projecting neurons in the retina, and their axons form the optic nerve. These central nerve axons originate at the RGC bodies located in the neural retina, travel along the nerve fibre layer converging to the optic disk and finally exit the eye through the optic nerve head (ONH). Glaucomatous optic neuropathy is a complex, multifactorial and heterogeneous human chronic neurodegenerative disease that characteristically affects the RGC population and their axons. It is a slowly progressive form of optic nerve damage and blindness that begins with loss of peripheral vision and is followed by gradual narrowing of the remaining central vision. Glaucoma currently affects over 70 million people (Quigley, 1996). Second only to cataract is the leading cause of irreparable blindness. This disease affects all age groups, but is more frequent in the elderly (Quigley & Vitale, 1997). Glaucoma is broadly classified into three main groups, i) primary open glaucoma (POAG); ii) primary acute closed angle glaucoma; and iii) primary congenital glaucoma. Among these, the most frequent is POAG (Shields et al., 1996). In this type of glaucoma the main risk factors are age and an elevated intraocular pressure (IOP). In most cases, lowering the IOP has a beneficial effect on RGC survival. However, some individuals with low or even normal IOP develop this disease with associated RGC loss, yet others with high IOP do not develop glaucoma or lose these neurons. Because of this, it has been proposed that there are genetic variants in humans that affect the relative susceptibility or resilience of RGCs to the same insult. This hypothesis is based on recent works showing that RGCs from different mice strains have an intrinsically different resistance to optic nerve injury. Li et al (2007) analyzed the survival of RGCs in 15 mice strains after optic nerve crush, and found that RGCs from the DAB/2J strain were the most resistant, while the ones from BALB/cByJ were the most susceptible. Interestingly, this