Whole genome assessment of the retinal response to diabetes reveals a progressive neurovascular inflammatory response

<p>Abstract</p> <p>Background</p> <p>Despite advances in the understanding of diabetic retinopathy, the nature and time course of molecular changes in the retina with diabetes are incompletely described. This study characterized the functional and molecular phenotype of the retina with increasing durations of diabetes.</p> <p>Results</p> <p>Using the streptozotocin-induced rat model of diabetes, levels of retinal permeability, caspase activity, and gene expression were examined after 1 and 3 months of diabetes. Gene expression changes were identified by whole genome microarray and confirmed by qPCR in the same set of animals as used in the microarray analyses and subsequently validated in independent sets of animals. Increased levels of vascular permeability and caspase-3 activity were observed at 3 months of diabetes, but not 1 month. Significantly more and larger magnitude gene expression changes were observed after 3 months than after 1 month of diabetes. Quantitative PCR validation of selected genes related to inflammation, microvasculature and neuronal function confirmed gene expression changes in multiple independent sets of animals.</p> <p>Conclusion</p> <p>These changes in permeability, apoptosis, and gene expression provide further evidence of progressive retinal malfunction with increasing duration of diabetes. The specific gene expression changes confirmed in multiple sets of animals indicate that pro-inflammatory, anti-vascular barrier, and neurodegenerative changes occur in tandem with functional increases in apoptosis and vascular permeability. These responses are shared with the clinically documented inflammatory response in diabetic retinopathy suggesting that this model may be used to test anti-inflammatory therapeutics.</p

The effect of previous surgery and topical eye drops for primary open-angle glaucoma on cytokine expression in aqueous humor

To evaluate cytokine expression in the aqueous humor of patients with primary open-angle glaucoma (POAG) after previous glaucomatous and/or cataract surgery, and to determine the effect of intraocular pressure (IOP)-lowering eye drops on cytokine expression. This prospective consecutive case study included 32 eyes diagnosed with POAG (19 with previous surgery and 13 without previous surgery, treated with topical antiglaucoma medication) and 12 eyes without signs of glaucoma. The Luminex 200 multiplex bead immunoassay was used to measure 27 cytokines in aqueous humor. Eyes suffering from POAG, with previous surgery, had significantly elevated concentrations of IL-6, IL-8, CCL2, CXCL9, and HGF, and a significantly lower concentration of CCL5, compared to POAG eyes without previous surgery, treated only with topical antiglaucoma medication. When compared with cataract controls, eyes with POAG and previous surgery had significantly elevated levels of G-CSF, IL-8, IL-12, CXCL10, and HGF, and significantly decreased concentrations of IL-17, CCL5, and VEGF in aqueous humor. In a comparison between POAG eyes without previous surgery and cataract controls, the cataract control eyes had significantly higher levels of IL-6 and CCL2, as the only significant difference. POAG is associated with an aqueous inflammatory response in the aqueous humor, which is significantly elevated in eyes with previous surgery. In contrast, preoperative IOP-lowering eye drops did not significantly alter the anterior chamber milieu. The results of the current study indicate that filtration surgery has a higher success rate in eyes that have not experienced previous surgery