Steroid hormones, particularly estrogens, modulate neuronal survival in the central nervous system and the retina; however, their specific cell-type-specific roles in the human retina remain incomplet Show more
Steroid hormones, particularly estrogens, modulate neuronal survival in the central nervous system and the retina; however, their specific cell-type-specific roles in the human retina remain incompletely characterized. We analyzed the single-cell RNA sequencing dataset E-MTAB-7316 to profile genes from the KEGG steroid hormone biosynthesis and oestrogen signalling pathways. Functional relevance of local oestrogen synthesis was tested in mouse retinal explants treated with the aromatase inhibitor letrozole (20āĪ¼M). Over 50% of steroid hormone metabolism genes were expressed in retinal cells, with cell-type specificity. COMT, HSD17B12, and HSD11B1L were broadly distributed, while LRTOMT, HSD17B7, and SRD5A1 were enriched in rod photoreceptors. Among oestrogen signalling genes, 114/139 were detected, with HSP90AA1 as the most abundant. When oestrogen synthesis was blocked with letrozole, retinal explants showed increased cell death, particularly in the outer nuclear layer, without inducing macrogliosis but with significant microglial activation (IBA1+). Our data indicate that the human retina expresses multiple components of steroid hormone metabolism and oestrogen signalling. The results are consistent with a potential role of locally synthesized oestrogens in photoreceptor maintenance and immune regulation, which may warrant further investigation as a possible avenue for retinal protection. Show less
Understanding molecular basis involved in overweight is an important first step in developing therapeutic pathways against excess in body weight gain. The purpose of our pilot study was to evaluateĀ th Show more
Understanding molecular basis involved in overweight is an important first step in developing therapeutic pathways against excess in body weight gain. The purpose of our pilot study was to evaluateĀ the gene expression profiles in the peripheral blood of obese patients without other metabolic complications. A sample of 17 obese patients without metabolic syndrome and 15 non obese control subjects was evaluated in a prospective way. Following 'One-Color Microarray-Based Gene Expression Analysis' protocol Version 5.7 (Agilent p/n 4140-90040), cRNA was hybridized with Whole Human Genome Oligo Microarray Kit (Agilent p/n G2519F-014850) containing 41,000+ unique human genes and transcripts. The average age of the study group was 43.6Ā Ā±Ā 19.7 years with a sex distribution of 64.7% females and 35.3% males. No statistical differences were detected with healthy controls 41.9Ā Ā±Ā 12.3 years with a sex distribution of 70% females and 30% males. Obese patients showed 1436 genes that were differentially expressed compared to control group. Ingenuity Pathway Analysis showed that these genes participated in 13 different categories related to metabolism and cellular functions. In the gene set of cellular function, the most important genes were C-terminal region of Nel-like molecule 1 protein (NELL1) and Pigment epithelium-derived factor (SPEDF), both genes were over-expressed. In the gene set of metabolism, insulin growth factor type 1 (IGF1), ApoA5 (apolipoprotein subtype 5), Foxo4 (Forkhead transcription factor 4), ADIPOR1 (receptor of adiponectin type 1) and AQP7 (aquaporin channel proteins7) were over expressed. Moreover, PIKFYVE (PtdIns(3) P 5-kinase), and ROCK-2 (rho-kinase II) were under expressed. We showed that PBMCs from obese subjects presented significant changes in gene expression, exhibiting 1436 differentially expressed genes compared to PBMCs from non-obese subjects. Furthermore, our data showed a number of genes involved in relevant processes implicated in metabolism, with genes presenting high fold-change values (up-regulation and down regulation) associated with lipid, carbohydrate and protein metabolism. Show less