Retinal Ganglion Cells-Diversity of Cell Types and Clinical Relevance

Abstract

Retinal ganglion cells (RGCs) are the bridging neurons that connect the retinal input to the visual processing centres within the central nervous system. There is a remarkable diversity of RGCs and the various subtypes have unique morphological features, distinct functions, and characteristic pathways linking the inner retina to the relevant brain areas. A number of psychophysical and electrophysiological tests have been refined to investigate this large and varied population of RGCs. Technological advances, such as high-resolution optical coherence tomography imaging, have provided additional tools to define the pattern of RGC involvement and the chronological sequence of events in both inherited and acquired optic neuropathies. The mechanistic insights gained from these studies, in particular the selective vulnerability and relative resilience of particular RGC subtypes, are of fundamental importance as they are directly relevant to the development of targeted therapies for these invariably progressive blinding diseases. This review provides a comprehensive description of the various types of RGCs, the developments in proposed methods of classification, and the current gaps in our knowledge of how these RGCs are differentially affected depending on the underlying aetiology. The synthesis of the current body of knowledge on the diversity of RGCs and the pathways that are potentially amenable to therapeutic modulation will hopefully lead to much needed effective treatments for patients with optic neuropathies.

Keywords: acquired optic neuropathies; electrophysiological tests; hereditary optic neuropathies; neuro-ophthalmology; optic neuropathies; retinal ganglion cell.

Figure 1

Schematic description of retinal ganglion cells. Morphological types of RGCs are classified based on soma size and dendrite morphology (by Ungsoo S. Kim).

Figure 2

Pathways of retinal ganglion cells. OPN, olivary pretectal nucleus; RGCs, retinal ganglion cells; SC, superior colliculus; SCN, suprachiasmatic nucleus (by Ungsoo S. Kim).

Figure 3

Receptive fields and responses of ON-centre, OFF-centre, and ON/OFF retinal ganglion cells. ON-centre RGCs (upper panels) increase their rate of discharge when the light illuminates in the centre. However, when the surround field is illuminated, the ON-centre RGCs are suppressed. OFF-center RGCs respond when the light turns off (middle panels). ON/OFF cells are triggered briefly when the light turns on or off (lower panels) (by Ungsoo S. Kim).

Figure 4

Melanopsin-containing intrinsically photosensitive RGCs in primates. Inner stratifying ipRGCs (M2 ipRGCs) have larger soma and more branched dendrites than outer stratifying ipRGCs. In addition, the dendrites of M1 ipRGCs are mainly located in the outer IPL layer, whereas M2 ipRGCs are in the outer IPL layer close to the ganglion cell layer. M1 ipRGCs project to the suprachiasmatic nucleus (SCN) to synchronize the circadian clock and M2 ipRGCs project to the olivary pretectal nucleus (OPN) in the thalamus to control pupillary response. A, amacrine cell; Off-B, Off-bipolar cell; On-B, On-bipolar cell (by Ungsoo S. Kim).

Figure 5

Pattern of RGC involvement in optic neuropathies. The types of RGCs affected in inherited optic neuropathies and acquired optic neuropathies are indicated by black and red lines, respectively. The dotted green line indicates the preservation of ipRGCs in inherited optic neuropathies. ADOA, autosomal dominant optic atrophy; FDT, frequency doubling technology; ipRGCs, intrinsically photosensitive retinal ganglion cells; LHON, Leber hereditary optic neuropathy; mRGCs, midget retinal ganglion cells; pRGCs, parasol retinal ganglion cells; sbRGCs, small bistratified retinal ganglion cells; smRGCs, smooth monostratified RGCs; SWAP, short wavelength automated perimetry (by Ungsoo S. Kim).