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Editors Selection IGR 23-4

Basic Science: Histo-architectural effects of IOP

Michael Girard

Comment by Michael Girard on:

108138 Who bears the load? IOP-induced collagen fiber recruitment over the corneoscleral shell, Foong TY; Hua Y; Amini R et al., Experimental Eye Research, 2023; 230: 109446


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The corneoscleral shell could play a pivotal role in enhancing our comprehension of glaucoma's development and progression. Beyond its crucial role in maintaining the optical integrity of the eye, its posterior part protects the delicate optic nerve head (ONH). This shielding mechanism is thought to be achieved through the precisely organized collagen fibers within the peripapillary and posterior sclera, thus serving as a resilient barrier against mechanical insults stemming from fluctuating intraocular pressure (IOP) and other external loads. Conversely, the anterior segment of the corneoscleral shell has been recognized as a potential biomarker for glaucoma. It has occasionally been proposed as a surrogate indicator for axonal damage in select, though not all, types of glaucoma. The supposition is that corneal collagen composition might mirror that of the ONH, thus providing a basis for these associations.

Given the potential significance of collagen microstructure in glaucoma, the authors aimed to assess the recruitment of collagen fibers as a function of IOP (at either physiological or elevated levels) and whether such responses were heterogeneous. In this context, a recruited fiber is defined as one that has straightened (due to IOP-induced stretching), consequently assuming load-bearing capabilities, and no longer exhibiting a 'wavy,' 'crimped,' or 'tortuous' configuration. In essence, the authors' primary objective was to ascertain the proportion of collagen fibers contributing to the load-bearing function under IOP-induced stress in various regions of the corneoscleral shell.

To this end, the authors developed an elegant strategy to make such measurements using human donor eyes. First, they imaged (using polarization light microscopy) and mapped collagen crimp over the entire corneoscleral shell in nine human donor eyes. Second, they used a computational model to simulate how such fibers would unfold for two levels of IOP, i.e. baseline at 15 mmHg, and elevated at 50 mmHg. Using such an approach, the authors successfully established the rate at which collagen fibers transitioned from a crimped to an uncrimped state (i.e., became recruited) and precisely identified their specific locations within the corneoscleral shell.

Overall, the authors found that fiber recruitment was highly heterogeneous. At baseline IOP, fibers were recruited the fastest in the posterior sclera (90% of fibers were recruited) as opposed to ~30% in the cornea and peripapillary sclera. Surprisingly, at an IOP of 50 mmHg, fibers were fully recruited across the shell, except at the equator and in the peripapillary sclera (70% recruitment only).

This study offers a comprehensive view of the intricacies of the eye as a mechanical system. Firstly it tells us that the rate of stiffening with IOP is going to differ considerably in different regions of the corneoscleral shell. Secondly, it reinforces that summarizing eye rigidity with a single parameter is not feasible, as tissue stiffness exhibits heterogeneity, but also changes in tissue stiffness with IOP. Thirdly, it indicates that even at an elevated IOP of 50 mmHg, not all fibers in certain eye regions are fully recruited, suggesting the presence of a reserve capacity to adapt to additional loads.

The proposed work exhibits merit, and there are several aspects worth considering for future enhancements. For instance, the authors might contemplate incorporating experimental validations of recruitment under varying levels of IOP. Additionally, expanding the scope of the research to encompass other crucial loads that could contribute to glaucoma, such as optic nerve traction, cerebrospinal fluid pressure, and others, could offer valuable insights.

Finally, it is worth noting that if fiber recruitment could be measured in vivo, it has the potential to inform us about which ONHs are more likely to withstand mechanical stress across a wide spectrum of internal and external biomechanical loads, and which ones might be more susceptible to failure, leading to neural and connective tissue damage.



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