Transneuronal Degeneration in the Brain During Glaucoma

Abstract

The death of retinal ganglion cells (RGCs) is a key factor in the pathophysiology of all types of glaucoma, but the mechanism of pathogenesis of glaucoma remains unclear. RGCs are a group of central nervous system (CNS) neurons whose soma are in the inner retina. The axons of RGCs form the optic nerve and converge at the optic chiasma; from there, they project to the visual cortex via the lateral geniculate nucleus (LGN). In recent years, there has been increasing interest in the dysfunction and death of CNS and retinal neurons caused by transneuronal degeneration of RGCs, and the view that glaucoma is a widespread neurodegenerative disease involving CNS damage appears more and more frequently in the literature. In this review, we summarize the current knowledge of LGN and visual cortex neuron damage in glaucoma and possible mechanisms behind the damage. This review presents an updated and expanded view of neuronal damage in glaucoma, and reveals new and potential targets for neuroprotection and treatment.

Transneuronal Degeneration in the Visual Pathway of Rats following Acute Retinal Ischemia/Reperfusion

“…It has been demonstrated that intervention measures that only compete against the mechanisms of in situ RGC death cannot satisfactorily recover the degenerated visual function following RI/R. Regrettably, previous research merely focused on preventing RGCs from death [27,31], while ignoring the transneuronal degeneration following RI/R [32]. Presently, we found that relay cell edema, intracellular mitochondrial proliferation, and the increase in the number of presynaptic vesicles and mitochondria in IPL were emerged in the early stage after RI/R injury (2 hours to 12 hours, RGCs did not appear to be significantly lost).…”

“…It has been demonstrated that intervention measures that only compete against the mechanisms of in situ RGC death cannot satisfactorily recover the degenerated visual function following RI/R. Regrettably, previous research merely focused on preventing RGCs from death [ 27 , 31 ], while ignoring the transneuronal degeneration following RI/R [ 32 ].…”

Ocular Neurodegenerative Diseases: Interconnection between Retina and Cortical Areas

“…Therefore, trans-synaptic degeneration is a process that spreads damage from the initial site to neuronal projections. Such a trans-synaptic degeneration has been long proven in the motor system and cerebellar pathways; only over the last decades, the presence of retrograde trans-synaptic degeneration has been highlighted in the human visual system, with particular relation to glaucoma [ 52 , 53 , 54 ]. It contributes to visual impairment observed in association with other various diseases, including, for example, multiple sclerosis [ 55 ].…”

“…Glaucoma is currently one of the most common causes of irreversible visual impairment and blindness in the world [ 80 ]; it includes a group of heterogeneous eye diseases, with closed-angle glaucoma and open-angle glaucoma the two main types. Generally, glaucoma is due to the increase in the internal pressure of the eye, that is, the intraocular pressure (IOP), which irreparably damages neurons; in some cases the reduction of the blood supply to the optic nerve, which cause loss of visual field, is involved [ 54 , 81 ]. In recent years, the literature argues in favor of the fact that glaucoma is a widespread neurodegenerative disease involving the CNS, as the correlation is strong between the dysfunction and death of CNS neurons with retinal ones.…”

Risk Factors for Retinal Ganglion Cell Distress in Glaucoma and Neuroprotective Potential Intervention

“…Glaucoma represents a group of neurodegenerative diseases characterized by optic nerve damage and the slow progressive death of retinal ganglion cells (RGCs). Indeed, glaucoma is regarded as the second cause of irreversible blindness worldwide and it is estimated that its incidence will increase to more than 112 million cases in the future [ 1 , 2 , 3 ].…”