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L. Blanchon, F. Chiambaretta, G. Marceau, H. Nezzar, D. Rigal, B. Yue, V. Sapin; Metabolic and Molecular Signalling Pathways of Retinoids on Human Trabecular meshwork. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3152.
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The integrity of the human ocular surface has an absolute requirement of vitamin A and its active derivatives, the retinoic acids. These retinoids act through the activation of nuclear receptors: RARS and RXRs. These receptors have been studied in rabbit, mouse and human cornea, but tissue and cellular expression of the 3 RARs and 3 RXRs had to be established at the human trabecular meshwork. The first objective of this work was to define their expression patterns in term of genes and proteins . The second objective was to demonstrate the presence of differents enzymes transforming vitamin A to retinoic acid and the activity of this retinoids pathway in the ocular surface.
Total mRNA was extracted from total human trabeculum meshwork, primary cell cultures of human trabecular mershwork established from donor corneas, and submitted to RT-PCR experiments. Immunological staining experiments were performed to better defi ne the RARs and RXRs protein localization. The expression patterns of retinal deshydrogenase (RALDHs) and alcohol deshydrogenase (ALDHs) was also determined in human trabecular meshwork cells. The metabolic pathway is tested by targeted disruption of diff erent enzyme steps transforming retinol to retinoids.
RAR alpha, beta, gamma, RXR alpha, ALDH4 and RALDH2 are expressed in trabecular meshwork. Trabecular cell meshworks are able to convert retinol into retinoic acid.
For the first time, we established an exhaustive description of RARs and RXRs, ALDHs and RALDHs expression patterns, in the human trabecular meshwork. Our results demonstrated in the human trabecular meshwork, the presence of all the actors of retinoic acid signalling pathway and their activation.
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