Dataset Information

Does Retinal Ganglion Cell Loss Precede Visual Field Loss in Glaucoma?

ABSTRACT: It is often said that substantial retinal ganglion cells are lost before glaucomatous damage is detected by standard automated perimetry. There are 4 key articles referenced to support this belief. To test the hypothesis that the 4 key articles are incorrectly cited, the publications in the first 6 months of 2019 that reference 1 or more of these 4 articles were examined. In particular, the degree to which the quotes from these 2019 publications accurately reflected the evidence in the 4 key articles was assessed. These quotes are inadequately supported by the data, and in some cases even by the conclusions found in the abstracts of the key articles. This is despite several review articles that have questioned the evidence in these key articles. Further, a case can be made that the evidence in the key articles better supports the opposite conclusion. That is, the data suggest that sensitivity loss can be seen on standard automated perimetry before retinal ganglion cells are missing.

SUBMITTER: Hood DC

PROVIDER: S-EPMC7343057 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Does Retinal Ganglion Cell Loss Precede Visual Field Loss in Glaucoma?

Hood Donald C DC

Journal of glaucoma 20191101 11

It is often said that substantial retinal ganglion cells are lost before glaucomatous damage is detected by standard automated perimetry. There are 4 key articles referenced to support this belief. To test the hypothesis that the 4 key articles are incorrectly cited, the publications in the first 6 months of 2019 that reference 1 or more of these 4 articles were examined. In particular, the degree to which the quotes from these 2019 publications accurately reflected the evidence in the 4 key art ...[more]

PMID: 31688445

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Project description:The pleotropic cytokine interleukin-6 (IL-6) is implicated in retinal ganglion cell (RGC) survival and degeneration, including that associated with glaucoma. IL-6 protects RGCs from pressure-induced apoptosis in vitro. However, it is unknown how IL-6 impacts glaucomatous degeneration in vivo. To study how IL-6 influences glaucomatous RGC axonopathy, accompanying glial reactivity, and resultant deficits in visual function, we performed neural tracing, histological, and neurobehavioral assessments in wildtype (B6;129SF2/J; WT) and IL-6 knock-out mice (B6;129S2-IL6tm1kopf/J; IL-6-/-) after 8 weeks of unilateral or bilateral microbead-induced glaucoma (microbead occlusion model). IOP increased by 20% following microbead injection in both genotypes (p < 0.05). However, deficits in wound healing at the site of corneal injection were noted. In WT mice, elevated IOP produced degenerating axon profiles and decreased axon density in the optic nerve by 15% (p < 0.01). In IL-6-/- mice, axon density in the optic nerve did not differ between microbead- and saline-injected mice (p > 0.05) and degenerating axon profiles were minimal. Preservation of RGC axons was reflected in visual function, where visual acuity decreased significantly in a time-dependent manner with microbead-induced IOP elevation in WT (p < 0.001), but not IL-6-/- mice (p > 0.05). Despite this preservation of RGC axons and visual acuity, both microbead-injected WT and IL-6-/- mice exhibited a 50% decrease in anterograde CTB transport to the superior colliculus, as compared to saline-injected controls (p < 0.01). Assessment of glial reactivity revealed no genotype- or IOP-dependent changes in retinal astrocytes. IOP elevation decreased microglia density and percent retinal area covered in WT mice (p < 0.05), while IL-6-/- mice exhibited only a decrease in density (p < 0.05). Together, our findings indicate that two defining features of RGC axonopathy-axon transport deficits and structural degeneration of axons-likely occur via independent mechanisms. Our data suggest that IL-6 is part of a mechanism that specifically leads to structural degeneration of axons. Furthermore, its absence is sufficient to prevent both structural degeneration of the optic nerve and vision loss. Overall, our work supports the proposition that functional deficits in axon transport represent a therapeutic window for RGC axonopathy and identify IL-6 signaling as a strong target for such a therapeutic.

Dataset Information

Does Retinal Ganglion Cell Loss Precede Visual Field Loss in Glaucoma?

Publications

Does Retinal Ganglion Cell Loss Precede Visual Field Loss in Glaucoma?

Similar Datasets

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