Abstract
Purpose :
To investigate effects of acute IOP elevation on structural abnormalities in the post-trabecular aqueous outflow tract of normal cats and cats homozygous for LTBP2 mutation, causal for FCG, prior to spontaneous, sustained IOP elevation.
Methods :
0.4% indocyanine green aqueous angiography (AA) and anterior segment optical coherence tomography (OCT) was performed ex vivo at physiological pressure (15 mmHg) in 14 cannulated eyes from 14 cats at 10-12 wks of age (7 FCG and 7 age-matched control) <2hrs postmortem, imaged by Spectralis HRA+OCT (Heidelberg Engineering). Additionally, 4 eyes per group were imaged 30 mins after IOP elevation (45 mmHg). Images were then exported, and scleral vessel shape was analyzed in 4 different images/quadrant/eye using ImageJ (v1.53n). Eyes were perfusion fixed with 4% PFA for 30 minutes following AA, and were routinely paraffin embedded, sectioned and stained. Morphometric analysis and quantitative assessment of collagen orientation surrounding scleral vessels was performed in each eye in H&E and Picrosirius Red stained sections by polarized light microscopy. Statistical comparisons were performed in GraphPad Prism (v.9.3.1).
Results :
All but one cat (an LTBP2 mutant) exhibited homogenous, circumferential AA outflow signal <10mins after tracer perfusion. Scleral lumen minor axis was smaller in LTBP2-mutant FCG eyes relative to controls (P=0.0004), and in all feline eyes lumens appeared partially collapsed after acute IOP elevation (P<0.001). Scleral vessel lumens in FCG cats appeared significantly collapsed and posteriorly displaced when compared to age matched controls. Scleral collagen orientation differed between FCG and normal cats, especially in anterior perivascular regions.
Conclusions :
Differences in perivascular scleral collagen organization, scleral vessel profile and their response to increased IOP were identified in this congenital glaucoma model prior to sustained, spontaneous IOP elevation.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.