Abstract
Purpose :
Primary congenital glaucoma (PCG) is an important cause of irreversible childhood blindness. LTBP2 mutations have been identified as causative for both human and feline PCG, but mechanisms of intraocular pressure (IOP) elevation remain unknown. We hypothesized that LTBP2 mutation causes pathology in the conventional aqueous outflow pathway. Ultrastructure of the trabecular meshwork (TM) was studied by transmission electron microscopy (TEM) and aqueous angiography (AA) evaluated more distal components of the outflow pathway in feline eyes, prior to and at the onset of significant IOP elevation.
Methods :
Eyes from 11 LTBP2-/- cats (2 neonates and 9 at 10- 12wks) and 6 age-matched control eyes (1 neonate and 5 at 10-12wks) were paraformaldehyde fixed, anterior segments dissected, and sectors post-fixed in glutaraldehyde, osmicated and processed and sectioned for TEM. To evaluate distal aqueous outflow pathways, indocyanine green AA was performed in 1 PCG (10- 12 wks) and 5 aged-matched control eyes <2hrs post-mortem, imaged by Spectralis HRA+OCT (Heidelberg Engineering).
Results :
The angle appeared open and TM and angular aqueous plexus (AAP; analogous to Schlemm’s canal) were visualized by TEM in both normal and mutant cats. In neonates, the still immature TM and AAP were morphologically comparable between PCG and control eyes. However, at 10-12wks, differences were evident between the two groups. In eyes of PCG cats, TM cells had an elongated, attenuated appearance and the inter-trabecular spaces of the corneoscleral TM appeared collapsed, with lower percentage of open space (P= 0.0006) relative to controls. Subjectively, TM beams appeared similar between groups, with regular collagen bundles and elastin cores, but less fibrillar material surrounding the core structure of the more proximal TM beams in PCG. The AAP and distal outflow channels still appeared patent in the juvenile PCG cats as supported by AA and OCT. All 10-12 wk-old cats regardless of disease status had nearly 360° circum-limbal AA signal, visible within <5 mins of commencing tracer perfusion.
Conclusions :
In this model of PCG related to LTBP2 mutation, TM, inter-trabecular spaces, AAP and more distal outflow pathways appear normal at birth. Subsequent development of TM cellular pathology and TM and JCT ECM pathology coincides with onset of IOP elevation.
This is a 2021 ARVO Annual Meeting abstract.