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Editors Selection IGR 11-1
IOP-Related
Comment by Alfredo Sadun on:
22844 Enhanced survival of melanopsin-expressing retinal ganglion cells after injury is associated with the PI3 K/Akt pathway, Li S-Y; Yau S-Y; Chen B-Y et al., Cellular and molecular neurobiology, 2008; 28: 1095-1107
The paper by Li et al. (363) is important, especially to students of glaucoma, in showing selective survival of a subclass of Retinal Ganglion Cells (RGCs) in models of optic-nerve injury. But before we discuss their findings and implications, we need to revisit this remarkable new class of retinal cells. Melanopsin RGCs, more often referred to as intrinsically photosensitive retinal ganglion cells (ipRGC), were described by Provencio and colleagues in the 1990s in mice. These cells are remarkable in that they represent a fifth class of receptor in the retina. However, unlike the rods and three cones, these cells are not only percipient but also direct some of their signal out of the retina through axons that run in the optic nerve. These constitute direct retinal projections to the pretectum (for the pupillary reflex) and hypothalamus (for light entrainment of the circadian rhythm). Melanopsin RGCs have a unique physiology with sensitivity to blue light (about 475 nm) and a sustained electrophysiologic response. This makes sense, as they do not contribute to formed vision. It's interesting to note that melanopsin has a distinct and ancient evolutionary lineage. The authors showed, in a rat model, that melanopsin RGCs may selectively survive optic nerve insults such as increased intraocular pressure or transection. That melanopsin RGCs may be more robust to some diseases of the eye has important implications that also pertain to mechanisms of pathophysiology in hereditary optic neuropathies (Leber's hereditary optic neuropathy and autosomal dominant optic atrophy). These authors have taken this concept beyond mere phenomenology. They provided evidence of a pathway that may protect melanopsin RGCs from certain insults. Then they blocked this pathway with intravitreous injection of a specific PI3 K/Akt inhibitor and found the selective sparing of melanopsin RGCs to be attenuated. This doesn't prove that melanopsin RGCs are intrinsically robust for having the PI3 K/Akt pathway. Apoptosis is not a serial or simple event. There are many pro- and anti- apoptotic factors whose interplay is very complicated. But this work is important in demonstrating that different RGC types may depend on different survival strategies. Understanding these strategies may mark the beginning of a new era in glaucoma therapeutics.
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