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Editors Selection IGR 11-3

Basic Science: Astrocytes and capillaries in the ONH of various animal species

Comment by Harry Quigley on:

56340 Comparative quantitative study of astrocytes and capillary distribution in optic nerve laminar regions, Balaratnasingam C; Kang MH; Yu P et al., Experimental Eye Research, 2014; 121: 11-22

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In order to improve understanding of the pathogenesis of glaucoma, this investigation quantified the proportion of the optic nerve head (ONH) occupied by astrocytes and capillaries among five species. However, there are a number of limitations with this study.

Unfortunately, the authors did not study monkey and mouse ONH, the two most frequent animal models in experimental glaucoma studies.

The report included only six humans, ranging from 23 to 62 years of age. ONH tissues change dramatically with age, so this is too few to do an age study and too diverse to give information on the eye at the peak age of glaucoma (60-85 years). For the animal eyes, the ages are not given; several studies now show differences in glaucoma susceptibility by age in monkey, rat and mouse.

The authors' data indicate that astrocytes occupy almost 70% of the human lamina cribrosa. An optic disc of 1.5 mm diameter would have an area of 1.76 mm². There are ~1 million human ganglion cell axons of 1 micron diameter, occupying 0.78 mm² area or ~44% of the tissue. The report's finding is seemingly incompatible with the space needed for axons, connective tissue beams and blood vessels.

There are a number of other methodological issues. First, the investigators studied fixed tissue, thereby giving estimates for cellular density that potentially differ from fresh tissue. They assumed that all nuclei in the ONH and nerve were astrocytes, a choice inconsistent with the presence of endothelium, pericytes, laminar fibroblasts and oligodendrocytes. In the rat, they included some of the unmyelinated optic nerve as lamina cribrosa. In human eyes, they studied only one ONH area, missing the chance to look for regional differences that might underlie regional glaucoma damage.

Overall, the data are specific to the methods used, so that they are more useful as relative than absolute values. It is not clear how the quantification used here would be helpful in understanding glaucoma damage. There are no horse models of glaucoma, and pig and rabbit models have only rarely given quantifiable data. It will be interesting to see if follow-up studies can make these data relevant.

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