Remodeling of the Connective Tissue Microarchitecture of the Lamina Cribrosa Occurs Early in Experimental Glaucoma in the Monkey Eye

¹ Ocular Biomechanics Lab, Devers Eye Institute, Legacy Health System, Portland, Oregon, United States
² Department of Engineering Science, Wolfson Medical Vision Laboratory, University of Oxford, Oxford, United Kingdom
³ Optic Nerve Head Research Laboratory, Devers Eye Institute, Legacy Health System, Portland, Oregon, United States
⁴ Third Eye Diagnostics, Inc, Bethlehem, Pennsylvania, United States
⁵ Ocular Biomechanics Laboratory, Devers Eye Institute, Legacy Health System, Portland, Oregon, United States

^* To whom correspondence should be addressed. E-mail: cdowns{at}deverseye.org.

	Abstract

Purpose. To characterize the trabeculated connective tissue microarchitecture of the lamina cribrosa (LC) in terms of total connective tissue volume (CTV), connective tissue volume fraction (CTVF), predominant beam orientation, and material anisotropy in monkeys with early experimental glaucoma (EG). Methods. The optic nerve heads from three monkeys with unilateral EG and four bilaterally normal monkeys were three-dimensionally (3D) reconstructed from tissues perfusion fixed at an intraocular pressure (IOP) of 10 mmHg. A 3D segmentation algorithm was used to extract a binary, voxel-based representation of the porous LC connective tissue microstructure, which was regionalized into 45 sub-volumes and the following quantities calculated: total CTV within the LC; mean and regional CTVF; regional predominant beam orientation; and mean and regional material anisotropy. Results. Regional variation within the laminar microstructure was considerable within the normal eyes of all monkeys. The laminar connective tissue was generally most dense in the central and superior regions for the paired normal eyes and laminar beams were radially oriented at the periphery for all eyes considered. CTV increased substantially in EG eyes compared to contralateral normals (82%, 44%, 45% increase; P<0.05), but average CTVF changed very little (-7%, 1%, and -2% in the EG eyes). There were more laminar beams through the thickness of the LC in the EG eyes compared to their normal controls (46%, 18%, and 17% increase). Conclusion. The substantial increase in laminar CTV with little change in CTVF suggests that significant alterations in both connective and non-connective tissue components in the laminar region occur in the early stages of glaucomatous damage.

Key Words: glaucoma, optic nerve head, intraocular pressure, lamina cribrosa, histomorphometry, remodeling

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