Abstract
Purpose :
To quantify the morphology of astrocytes, connective tissue beams, and axonal compartments in post mortem human optic nerve heads (ONH), comparing control to glaucoma, central to peripheral ONH, and by degree of optic nerve damage.
Methods :
Serial cross-sections of 16 glaucoma ONH (from 12 donors, median age=79) and 9 control ONH (from 6 donors with no glaucoma history and normal optic nerves, median age=83) were immunolabelled for confocal and second harmonic generation imaging as described in Ling et al. 2019. 63 structural features of lamina cribrosa (LC) were measured, including astrocytic glial fibrillary acidic protein (GFAP) area fraction, actin area fraction, median axonal compartment area, average collagen beam width, and nuclei density. Global and regional differences were compared between controls and glaucoma, and among glaucoma severity groups judged by masked grading of axon loss in nerve cross-sections by two observers.
Results :
The area fraction of GFAP and actin in the LC pores was significantly decreased in glaucoma eyes (P = 0.014, 0.009, respectively) and these measures declined consistently with increased glaucoma damage (Figure 1). However, the mean area of LC pores was not significantly different in glaucoma eyes. Median axonal compartment area was significantly lower in glaucoma (P = 0.015). GFAP area fraction in pores was higher in periphery than center LC in both control and glaucoma (P = 0.057, P = 0.025, respectively). While in controls the mean collagen beam width was similar in central and peripheral regions, in glaucoma the beam width was significantly lower in peripheral than in central regions (P = 0.007).
Conclusions :
This cross-sectional, quantitative analysis of LC structure suggests that loss of axons in glaucoma is associated with reductions in astrocyte cytoskeletal components and axonal compartments, as well as progressive beam thinning.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.