PubMed ID: 39432401
Author(s): Torne O, Oikawa K, Teixeira LBC, Kiland JA, McLellan GJ. Trabecular Meshwork Abnormalities in a Model of Congenital Glaucoma Due to LTBP2 Mutation. Invest Ophthalmol Vis Sci. 2024 Oct 1;65(12):28. doi: 10.1167/iovs.65.12.28. PMID 39432401
Journal: Investigative Ophthalmology & Visual Science, Volume 65, Issue 12, Oct 2024
PURPOSE To characterize early trabecular meshwork (TM) morphologic abnormalities in a feline model of human primary congenital glaucoma (PCG) caused by mutation in LTBP2.
METHODS Eyes from 41 cats, including 19 normal and 22 homozygous for LTBP2 mutation, across various postnatal stages (birth, 2 weeks, 5 weeks, and 12 weeks) were paraformaldehyde fixed, anterior segments dissected, post-fixed in glutaraldehyde, osmicated, and processed and sectioned for transmission electron microscopy. Cell morphology, nuclear shape, and intertrabecular space (ITS) were quantitatively assessed, and the structure of the fibrillar extracellular matrix in the TM was systematically evaluated.
RESULTS The earliest differences in TM morphology between PCG and normal cats were identified at 2 weeks postnatally. Elastic fibers in the TM were discontinuous and disorganized (P = 0.0122), and by 5 weeks of age PCG cats presented significantly less ITS (P = 0.0076) and morphologically rounder TM cells than normal cats (P = 0.0293). By 12 weeks of age, the ITS was further collapsed (P < 0.0001), and the TM cells were morphologically elongated and attenuated in PCG compared to controls (P = 0.0028).
CONCLUSIONS In this feline model of PCG due to LTBP2 mutation, development of ultrastructural TM extracellular matrix abnormalities are first observed by 2 weeks and cellular abnormalities by 5 weeks of age. By 12 weeks of age, when intraocular pressure becomes significantly elevated, the TM morphologic abnormalities are already well established. These findings suggest that the postnatal period between 0 and 5 weeks of age is critical for TM and PCG development and progression in cats.