Gene expression in the trabecular meshwork and the influence of intraocular pressure.
The trabecular meshwork (TM) tissue is responsible for maintaining the physiologic intraocular pressure (IOP) of the ocular globe. To perform this function the TM must rely on a variety of mechanisms. These mechanisms, acting either independently or in a coordinated manner, are governed by the expression of TM genes. Expression profiles of TM from adult intact tissue and infant cultured cells revealed the high level of diversity of the TM transcriptome, with only about 1% of its genes represented by more than 4 clones in any of the libraries. The profiles also revealed genes whose presence is associated with previously undescribed TM functions such the one that protects the TM tissue against calcification. These findings support the existence of numerous regulatory mechanisms in the TM and may help explaining the low percentage of glaucoma patients associated with each mutated glaucoma gene. Failure to maintain a physiological pressure can result in elevated IOP, a condition often associated with the development of glaucoma. Experimentally, different time-periods of an elevated pressure insult lead to the altered expression of distinct sets of genes. Thus, the ability of the TM to respond to mechanical and biochemical insults is possibly driven by induction or repression of a number of genes that, most likely, are different from those involved in regulation of normal IOP. None of the genes currently linked to glaucoma was present in the expression profile libraries whereas their expression in the TM was highly induced by effectors known to be causative of glaucomatous conditions. This analysis leads to the speculation that glaucoma candidate genes might be more related to genes responding to insults than to those involved in the maintenance of normal TM physiology. A recent study implicating the common stress mediator NF-kappaB in glaucoma would support this notion. Future library profiles utilizing distinct RNA sources together with differential expression studies between normal and glaucoma-triggering conditions and individual characterization of selected genes will help elucidate the relevant mechanisms for the regulation of IOP.
Borrás
Teresa
T
Department of Ophthalmology, University of North Carolina School of Medicine, 6109 Neuroscience Research Building, Campus, Box 7041, Chapel Hill, NC 27599, USA.
D015870:Gene Expression / Q000502:physiology*; D020869:Gene Expression Profiling; D005901:Glaucoma / Q000235:genetics; D006801:Humans; D007429:Intraocular Pressure / Q000502:physiology*; D014129:Trabecular Meshwork / Q000378:metabolism*