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Editors Selection IGR 11-3
Anatomical Structures: Lamina cribrosa structure
Comment by Claude Burgoyne on:
54840 Scleral structural alterations associated with chronic experimental intraocular pressure elevation in mice, Cone-Kimball E; Nguyen C; Oglesby EN et al., Molecular Vision, 2013; 19: 2023-2039
Carefully designed and interpreted rodent studies should eventually provide insight into the scleral contribution to optic nerve head (ONH) susceptibility in human glaucoma. In this report, Cone-Kimball and co-authors report differences in baseline scleral micro and macro architecture among four mice strains, (C57BL/6 (B6), CD1; collagen 8α2 mutant mice (Aca23) and their wild-type littermates (Aca23-WT)); differences in each mouse strain's scleral response to chronic IOP elevation; and differences in each strain's optic nerve axon susceptibility to chronic IOP elevation. This is a complicated study because of the number of species, the variety of measurements and the variety of outcomes. However, the subject is of substantial importance because the sclera should be an important biomechanical determinant of ONH susceptibility in species with and without a connective tissue lamina cribrosa. While rodent models possess 'only' a cellular lamina cribrosa (a 'benefit' on many levels), they also provide the opportunity to genetically manipulate the expression of selected scleral extracellular matrix proteins (i.e., the Aca23 strain which turned out to be the least susceptible to axon loss). Primary results suggested that dynamic responses of the mouse sclera to chronic experimental IOP elevation may be more important than baseline anatomic features in explaining susceptibility to damage. These responses included decreases in non-fibrillar components of the sclera, alterations in scleral lamellar orientation, an increased number of smaller collagen fibrils, fewer larger fibrils, and relative increase in the number and thickness of scleral fibroblast layers. This was a large study, with some understandable weaknesses. Chief among these were a small number of eyes in the optic nerve axon susceptibility study that did not allow the authors to detect what appear to be clear IOP insult differences as significant. In this case, the strains with the highest IOPs were least susceptible to axon loss so principle findings were not compromised. Additionally, while a very interesting finding, namely a 'splitting' of the superior peripapillary sclera (adjacent to or within the circumferential fibrous band) was seen in a subset of eyes, rigorous measurements of canal architecture were not done at baseline nor was change in this anatomy characterized over the course of chronic IOP elevation. While the authors are to be commended for advancing this field, this study suggests that a great deal of painstaking work remains to be done.
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