Sydney M Galindez1, Andrew Keightley1, Peter Koulen2,3. 1. School of Medicine, Vision Research Center, Department of Ophthalmology, University of Missouri - Kansas City School of Medicine, 2411 Holmes St, Kansas City, MO, 64108, USA. 2. School of Medicine, Vision Research Center, Department of Ophthalmology, University of Missouri - Kansas City School of Medicine, 2411 Holmes St, Kansas City, MO, 64108, USA. koulenp@umkc.edu. 3. Department of Biomedical Sciences, University of Missouri - Kansas City School of Medicine, Kansas City, MO, USA. koulenp@umkc.edu.
Abstract
BACKGROUND: The retinal pigment epithelium (RPE), a layer of pigmented cells that lies between the neurosensory retina and the underlying choroid, plays a critical role in maintaining the functional integrity of photoreceptor cells and in mediating communication between the neurosensory retina and choroid. Prior studies have demonstrated neurotrophic effects of select steroids that mitigate the development and progression of retinal degenerative diseases via an array of distinct mechanisms of action. METHODS: Here, we identified major steroid hormone signaling pathways and their key functional protein constituents controlling steroid hormone signaling, which are potentially involved in the mitigation or propagation of retinal degenerative processes, from human proteome datasets with respect to their relative abundances in the retinal periphery, macula, and fovea. RESULTS: Androgen, glucocorticoid, and progesterone signaling networks were identified and displayed differential distribution patterns within these three anatomically distinct regions of the choroid-retinal pigment epithelial complex. Classical and non-classical estrogen and mineralocorticoid receptors were not identified. CONCLUSION: Identified differential distribution patterns suggest both selective susceptibility to chronic neurodegenerative disease processes, as well as potential substrates for drug target discovery and novel drug development focused on steroid signaling pathways in the choroid-RPE.
BACKGROUND: The retinal pigment epithelium (RPE), a layer of pigmented cells that lies between the neurosensory retina and the underlying choroid, plays a critical role in maintaining the functional integrity of photoreceptor cells and in mediating communication between the neurosensory retina and choroid. Prior studies have demonstrated neurotrophic effects of select steroids that mitigate the development and progression of retinal degenerative diseases via an array of distinct mechanisms of action. METHODS: Here, we identified major steroid hormone signaling pathways and their key functional protein constituents controlling steroid hormone signaling, which are potentially involved in the mitigation or propagation of retinal degenerative processes, from human proteome datasets with respect to their relative abundances in the retinal periphery, macula, and fovea. RESULTS: Androgen, glucocorticoid, and progesterone signaling networks were identified and displayed differential distribution patterns within these three anatomically distinct regions of the choroid-retinal pigment epithelial complex. Classical and non-classical estrogen and mineralocorticoid receptors were not identified. CONCLUSION: Identified differential distribution patterns suggest both selective susceptibility to chronic neurodegenerative disease processes, as well as potential substrates for drug target discovery and novel drug development focused on steroid signaling pathways in the choroid-RPE.
Authors: Paramjit Kaur; Parmeet K Jodhka; Wendy A Underwood; Courtney A Bowles; Nancyellen C de Fiebre; Christopher M de Fiebre; Meharvan Singh Journal: J Neurosci Res Date: 2007-08-15 Impact factor: 4.164