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Editors Selection IGR 11-1

Basic Research: Source of ganglion cell replacement

Comment by David Calkins on:

26795 Amacrine cell gene expression and survival signaling: differences from neighboring retinal ganglion cells, Kunzevitzky NJ; Almeida MV; Goldberg JL, Investigative Ophthalmology and Visual Science, 2010; 51: 3800-3812

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Amacrine cells represent the most diverse neuronal cell class in the vertebrate retina, but perhaps the least understood. An estimated 30 distinct types provide essential signal modulation to the glutamatergic bipolar cellganglion cell circuit. Most amacrine cell types lack an axon and are relatively impervious to degeneration in optic neuropathies. These features are among the most fundamental distinguishing amacrine from ganglion cells. Yet, attempts to understand their phenotypic origins have been stymied by lack of a tractable approach to characterizing their genetic signature. In this paper, Kunzevitzky et al., (1087) directly compared the gene expression profiles of immuno-purified amacrine and ganglion cells to help determine their transcriptional differences. Perhaps not surprisingly, given they share a common progenitor, amacrine and ganglion cells shared most of the genes identified, nearly 75%. Where the two cell classes differed significantly was in genes associated with neurotransmission (ganglion cells) and genes associated with genetic activity (amacrine cells). These differences are consistent with the known physiological roles for these cells: transmitting visual signals through excitation (ganglion cells) vs. modulating signal processing in the inner retina through complex and diverse neurochemical pathways (amacrine cells).

With some genetic tweaking, could amacrine cells be a ready source of ganglion cell replacement?

Perhaps the most intriguing result in fact had little to do with gene expression profiling. The team used the same procedure to culture purified amacrine cells and asked if factors known to promote ganglion cell survival in culture would have a similar effect. Addition of trophic factors had little influence on amacrine cells; nor did culturing them at higher densities. Both are known to increase ganglion cell survival under similar conditions. What remain fundamental about these data are the implications. Amacrine cells, apparently, do not promote their own survival by homologous paracrine signaling. In contrast, interruption of a number of key intracellular kinases involved in cell proliferation and independent survival was detrimental to amacrine cell viability. The team suggests this very independence allows amacrine cells to survive optic neuropathies like glaucoma and could, with some genetic tweaking, render amacrines a ready source of ganglion cell replacements. This raises the question of whether the programming that allows axonal outgrowth and excitatory neurotransmission for ganglion cells might be, in normal development, incompatible with the programming that makes amacrine cells so self-sustaining.

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