Degeneration of retina-brain components and connections in glaucoma: Disease causation and treatment options for eyesight preservation

Abstract

Eyesight is the most important of our sensory systems for optimal daily activities and overall survival. Patients who experience visual impairment due to elevated intraocular pressure (IOP) are often those afflicted with primary open-angle glaucoma (POAG) which slowly robs them of their vision unless treatment is administered soon after diagnosis. The hallmark features of POAG and other forms of glaucoma are damaged optic nerve, retinal ganglion cell (RGC) loss and atrophied RGC axons connecting to various brain regions associated with receipt of visual input from the eyes and eventual decoding and perception of images in the visual cortex. Even though increased IOP is the major risk factor for POAG, the disease is caused by many injurious chemicals and events that progress slowly within all components of the eye-brain visual axis. Lowering of IOP mitigates the damage to some extent with existing drugs, surgical and device implantation therapeutic interventions. However, since multifactorial degenerative processes occur during aging and with glaucomatous optic neuropathy, different forms of neuroprotective, nutraceutical and electroceutical regenerative and revitalizing agents and processes are being considered to combat these eye-brain disorders. These aspects form the basis of this short review article.

Keywords: Axonal injury; Glaucoma; Intraocular pressure; Neurodegeneration; Neuroprotection; Optic nerve; Retina; Retinal ganglion cell.

Graphical abstract

Fig. 1

Anatomical location and connections between the eyes and the brain structures involved in visual information capture, transmission and perception upon decoding.

Fig. 2

Cartoon of the anterior segment of the human eye depicting key structures producing and draining the AQH is shown.

Fig. 3

Schematic illustration of the many sites of damage that can occur within the eye-brain axis due to chronically elevated IOP in POAG.

Fig. 4

Cartoon showing how raised IOP bulges the eye and causes mechanical pressure to radiate to all part of the eye but in particular how and where it causes damages at the ONH/LC regions (A). The molecular and cellular components affected by the elevated IOP at the level of the ONH/LC and optic nerve are depicted in more detail in panel B.

Fig. 5

The brain structures impacted by chronic ocular hypertension (OHT) or POAG at the lateral geniculate and visual cortical levels are shown.

Fig. 6

The deleterious effects glaucomatous optic neuropathy (GON) on retinal and brain structures and their dysfunctions resulting in various disabilities are depicted.