Mechanical strain in the mouse astrocytic lamina increases after exposure to recombinant trypsin

Korneva, Arina; Kimball, Elizabeth; Quillen, Sarah; Jefferys, Joan L.; Nawathe, Manasi; Ling, Yik Tung Tracy; Nguyen, Thao D.; Quigley, Harry A.

doi:10.1016/j.actbio.2022.02.023

Cited by 4 publications

(3 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 57 The effect is simulated by treatment of the mouse eye with trypsin, which both causes such disconnection and increases strain. 58 Our findings confirm in human OAG the reports from rat and monkey glaucoma models that astrocytes migrating into axonal bundles (pores) produce collagens at locations that are aberrant.…”

Section: Discussionsupporting

confidence: 87%

Quantitative Microstructural Analysis of Cellular and Tissue Remodeling in Human Glaucoma Optic Nerve Head

Guan

Pease

Quillen

et al. 2022

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Purpose To measure quantitatively changes in lamina cribrosa (LC) cell and connective tissue structure in human glaucoma eyes. Methods We studied 27 glaucoma and 19 age-matched non-glaucoma postmortem eyes. In 25 eyes, LC cross-sections were examined by confocal and multiphoton microscopy to quantify structures identified by anti-glial fibrillary acidic protein (GFAP), phalloidin-labeled F-actin, nuclear 4′,6-diamidino-2-phenylindole (DAPI), and by second harmonic generation imaging of LC beams. Additional light and transmission electron microscopy were performed in 21 eyes to confirm features of LC remodeling, including immunolabeling by anti-SOX9 and anti-collagen IV. All glaucoma eyes had detailed clinical histories of open-angle glaucoma status, and degree of axon loss was quantified in retrolaminar optic nerve cross-sections. Results Within LC pores, the proportionate area of both GFAP and F-actin processes was significantly lower in glaucoma eyes than in controls ( P = 0.01). Nuclei were rounder (lower median aspect ratio) in glaucoma specimens ( P = 0.02). In models assessing degree of glaucoma damage, F-actin process width was significantly wider in glaucoma eyes with more damage ( P = 0.024), average LC beam width decreased with worse glaucoma damage ( P = 0.042), and nuclear count per square millimeter rose with worse damage ( P = 0.019). The greater cell count in LC pores represented 92.3% astrocytes by SOX9 labeling. The results are consistent with replacement of axons in LC pores by basement membrane labeled by anti-collagen IV and in-migrating astrocytes. Conclusions Alteration in LC structure in glaucoma involves migration of astrocytes into axonal bundles, change in astrocyte orientation and processes, production of basement membrane material, and thinning of connective tissue beams.

show abstract

Section: Discussionsupporting

confidence: 87%

Quantitative Microstructural Analysis of Cellular and Tissue Remodeling in Human Glaucoma Optic Nerve Head

Guan

Pease

Quillen

et al. 2022

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

“…The estimated strains in untreated mouse eyes in this experiment were of similar magnitude to those previously measured by our lab using two other mouse types, one of whose astrocytes express green fluorescent protein under control of either the glutamate transporter (GLT1) promoter 53 and one in which the fluorescent marker is driven by the glial fibrillary acidic protein promoter. 29 Some differences among mouse types would be expected, as differences in eye size, pigmentation, genetic factors, and tissue behaviors may affect biomechanical responses. 42 , 44 The strains reported in human ONH both postmortem 45 , 54 and in living eyes 15 , 55 are also generally of similar magnitude, despite the anatomic differences and variations in level and duration of IOP changes.…”

Section: Discussionmentioning

confidence: 99%

“… 26 A similar alteration in the strain response was produced by short-term trypsin treatment to detach the astrocyte processes from the basement membrane. 29 In this study, we measure the strain response of the AL to ex vivo IOP elevation in eyes of experimental mice. We compare the strain response between the experimental glaucoma and the optic nerve crush at both 3 days and 6 weeks after initiation of the models.…”

mentioning

confidence: 99%

Comparison of the Biomechanics of the Mouse Astrocytic Lamina Cribrosa Between Glaucoma and Optic Nerve Crush Models

Korneva,

Kimball,

Johnson

et al. 2023

Invest. Ophthalmol. Vis. Sci.

Self Cite

View full text Add to dashboard Cite

Purpose The strain response of the mouse astrocytic lamina (AL) to an ex vivo mechanical test was compared between two protocols: eyes that underwent sustained intraocular pressure (IOP) increase and eyes after optic nerve crush. Methods Chronic IOP elevation was induced by microbead injection or the optic nerve was crushed in mice with widespread green fluorescence. After 3 days or 6 weeks, eyes were inflation tested by a published method of two-photon fluorescence to image the AL. Digital volume correlation was used to calculate strains. Optic nerve axon damage was also evaluated. Results In the central AL but not the peripheral AL, four strains were greater in eyes at the 3-day glaucoma time point than control ( P from 0.029 to 0.049, n = 8 eyes per group). Also, at this time point, five strains were greater in the central AL compared to the peripheral AL ( P from 0.041 to 0.00003). At the 6-week glaucoma time point, the strains averaged across the specimen, in the central AL, and the peripheral AL were indistinguishable from the respective controls. Strains were not significantly different between controls and eyes 3 days or 6 weeks after crush ( n = 8 and 16). Conclusions We found alterations in the ex vivo mechanical behavior in eyes from mice with experimental glaucoma but not in those with crushed optic nerves. The results of this study demonstrate that significant axon injury does not directly affect mechanical behavior of the astrocytic lamina.

show abstract

Special Issue: Mechanics of Cells and Fibers

2023

View full text Add to dashboard Cite

Mechanical strain in the mouse astrocytic lamina increases after exposure to recombinant trypsin

Cited by 4 publications

References 35 publications

Quantitative Microstructural Analysis of Cellular and Tissue Remodeling in Human Glaucoma Optic Nerve Head

Quantitative Microstructural Analysis of Cellular and Tissue Remodeling in Human Glaucoma Optic Nerve Head

Comparison of the Biomechanics of the Mouse Astrocytic Lamina Cribrosa Between Glaucoma and Optic Nerve Crush Models

Special Issue: Mechanics of Cells and Fibers

Contact Info

Product

Resources

About