Differential distribution of steroid hormone signaling networks in the human choroid-retinal pigment epithelial complex

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.

Causal Influence of Plasma Metabolites on Age-Related Macular Degeneration: A Mendelian Randomization Study.

“…The traditional AR pathway, found in the fovea but not in the macula, and alternative pathways involving speci c binding proteins, are present in various parts of the retina and are closely associated with sex hormones. Androgens, including metabolic derivatives of androstenediol, can also interact with GABAA receptors, which are located in areas of the central nervous system, including the retina [33]. The neuroprotective role of androgens, such as Androstenediol (3beta,17beta) monosulfate, is evident in their in uence on neural differentiation, survival, and development through the AR pathway [34].…”