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Editors Selection IGR 9-4

Basic Research: Loss of relay neurons in LGN

Yeni Yucel

Comment by Yeni Yucel on:

28034 Involvement of endoplasmic reticulum stress on neuronal cell death in the lateral geniculate nucleus in the monkey glaucoma model, Ito Y; Shimazawa M; Inokuchi Y et al., European Journal of Neuroscience, 2011; 33:843-855


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Ito et al. (44) examine the lateral geniculate nucleus in one normal and four monkeys with ocular hypertension for 4, 11, 15 and 24 weeks, looking for evidence of neuron loss, atrophy, apoptotic cell death and endoplasmic reticulum (ER) stress-related proteins. Their results regarding loss and atrophy of relay neurons in the lateral geniculate nucleus are consistent with previous reports on this subject, not correctly cited.1,2 In addition to the very small sample sizes, there are concerns regarding the statistical analysis of TUNELstain, polyubiquitin and all other stains related to ER stress-related proteins. The density of positively stained neurons in each of the six layers for every animal was considered an independent variable, and an ANOVA test with F1, 20 applied. This test is indicated for independent variables, and is not relevant here, since the examined layers are from the same animal, and cannot be considered independent. The density of TUNEL-positive cells ranges from 2 to 8 per layer. No double labelling was performed to determine whether these TUNELpositive cells are relay neurons, interneurons or glial cells. With only one normal control monkey that did not show TUNEL-positive cells, it is difficult to determine whether these results are significant and can explain neuron loss observed in glaucomatous lateral geniculate nucleus. However, these preliminary results should encourage these investigators to pursue the role of apoptotic neuronal loss in a larger sample size, with an appropriate number of normal controls. The wide density range in glaucoma monkeys from 0 to 20 cell/mm2, and from 0 to 18 cell/mm2 for ER stress-related proteins (p-eIF2α) and (CHOP), respectively, is not addressed. Furthermore, the relationship between these proteins and cell death may not be straightforward, as seen by the p-eIF2α-positive neuron that appears quite healthy (Figure 10 B, left panel). In fact, the role of p-eIF2α depends on specific kinases , and these can tip the balance toward cell survival or cell death.3 While the results are encouraging, rigorous studies are needed to understand the role of endoplasmic reticulum stress on brain changes in glaucoma.

References

  1. Y.H. Yücel, Q. Zhang, R.N. Weinreb, P.L. Kaufman and N. Gupta. Atrophy of relay neurons in magno-and parvocellular layers of the lateral geniculate nucleus in glaucoma. Investigative Ophthalmology and Visual Science. 42: 3216-3222, 2001.
  2. Y.H. Yücel, Q. Zhang, N. Gupta, P.L. Kaufman, and R.N. Weinreb. Loss of neurons in magno and parvocellular layers of the lateral geniculate nucleus in glaucoma. Archives of Ophthalmology. 118: 378-384, 2000.
  3. Muaddi H, Majumder M, Peidis P, Papadakis AI, Holcik M, Scheuner D, Kaufman RJ, Hatzoglou M, Koromilas AE.Phosphorylation of eIF2α at serine 51 is an important determinant of cell survival and adaptation to glucose deficiency. Mol Biol Cell. 2010 Sep 15;21(18):3220-31.


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