Discrete chorioretinal lesions and optic neuritis and inflammatory cells in the vitreous for toxoplasmosis and lattice retinal degeneration with bands in vitreous for Stickler’s disease. Differences in collagen expression might also affect angiogenesis and fibrogenesis, which both appear to affect ophthalmologic sequellae. It is of interest in this regard that host collagen genes are among those with increased expression when T. gondii infects fibroblasts. Levels of type II collagen mRNA decline in the eye post-natally, and continue to exhibit a slow age-dependent reduction. However, reactivation of type IIA collagen can occur at later stages, possibly during tissue repair, and may also modulate proliferative processes in the vitreous. Genetic differences in COL2A1 type IIA expression, triggered directly by the parasite and/or the tissue response to the parasite, could play a role in the continuing postnatal development of pathology associated with congenitally-acquired toxoplasmosis. Type IIA is the predominant isoform in non-cartilaginous and non-ocular tissues during embryogenesis, but there is a switch from type IIA to IIB as chondrocytes differentiate, making the shorter form IIB the predominant form in mature cartilage. This has important implications in relation to the lack of skeletal features in Ginsenoside-F2 clinical phenotypes observed in congenital toxoplasmosis, as discussed below in relation to the epigenetic silencing of the maternallyderived allele that we have observed for the type IIB isoform of COL2A1. ABCA4 encodes a retina-specific ATP-binding cassette transporter protein that is located at the rim of the photoreceptor outer segment disc and is involved in retinoid transport across the disc membrane. Less is known about the chronological pattern of expression of ABCA4 in the eye during development compared to COL2A1, although a high frequency of cDNA clones positive for ABCA4 has been reported in screens of cDNA libraries prepared from developing mouse eye. Of interest too is the observation is that ABCA4 is selectively expressed in the choroid plexus throughout development, suggesting a possible role for ABCA4 in determining pathology in brain in addition to eye, that would be consistent with the association observed with hydrocephalus, in particular when examining associations between mother’s genotype and clinical Mepiroxol outcome in the child for the European cohort.
The unusual patterns of inheritance of disease alleles that we observed when comparing association
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