Diabetic Retinopathy Is Associated with Decreased Tyrosine Nitrosylation of Vitreous Interleukins IL-1α, IL-1ß, and IL-7.

OBJECTIVE: To simultaneously evaluate tyrosine nitrosylation and phosphorylation levels of vitreous interleukins of patients with diabetic retinopathy, in which abnormal tyrosine phosphorylation has been previously described. RESEARCH DESIGN AND METHODS: Specific immunoprecipitation of interleukins IL-1α, IL-1ß, IL-2 and IL-7 was carried out in samples obtained during vitrectomy performed for proliferative diabetic retinopathy in patients (n=12) and for macular hole in controls (n=12). Tyrosine nitrosylation and phosphorylation levels of the immunoprecipitated interleukins were analysed by Western blot with the respective specific antibodies and correlated. The results were also correlated with the total amount of immunoprecipitated interleukin protein. The mean phosphorylation/nitrosylation ratios of these proteins in vitreous humour of both the control group and diabetic patients were determined. RESULTS: Diabetes was associated with decreased tyrosine nitrosylation of IL-1α, IL-1ß and IL-7 and an increased tyrosine phosphorylation/nitrosylation ratio with respect to controls in IL-1α (1.58±0.22 vs. 2.74±0.39, respectively; p<0.05) and IL-7 (2.15±0.01 vs. 3.26±0.57, respectively; p<0.05). No significant changes were observed in nitrotyrosine or in the tyrosine phosphorylation/nitrosylation ratio of IL-2. CONCLUSIONS: Proliferative diabetic retinopathy is associated with concomitant and simultaneous changes in both tyrosine phosphorylation and tyrosine nitrosylation status of specific pro-inflammatory interleukins present in the vitreous fluid such as IL-1α, IL-1ß and IL-7. These changes could be related to the increase in pro-inflammatory activity detected in diabetes-induced retinopathy.

Photodynamic therapy in the management of circumscribed choroidal hemangioma.

OBJECTIVE: To evaluate the efficacy of photodynamic therapy (PDT) for symptomatic circumscribed choroidal hemangioma (CCH). DESIGN: A retrospective case series analysis through chart review of patients with CCH treated by means of PDT. PARTICIPANTS: Thirteen patients with circumscribed choroidal hemangioma. METHODS: Through retrospective charts review, the patients' demographics, clinical features, management, and follow-up data were obtained and analyzed. Outcome measures were change in visual acuity, required sessions, and adjunctive treatments. RESULTS: Median follow-up was 26 months. Seven patients (54%) underwent only 1 session, 5 patients (38%) 2 sessions, and 1 received 5 sessions and was finally treated with external beam radiotherapy (EBRT). Visual acuity improved by at least 1 line (1-5) in 11 patients and remained stable in 2. Exudative subretinal fluid was completely resolved in 92% of the cases at the last visit. No major local side effects were found. CONCLUSIONS: PDT of CCH can effectively induce tumor regression and resolution of exudative subretinal fluid, improving, or stabilizing vision.

Tyrosine phosphorylation of vitreous inflammatory and angiogenic peptides and proteins in diabetic retinopathy.

PURPOSE: To evaluate the degree of phosphorylation of vitreous proteins in patients with type 2 diabetes mellitus and diabetic retinopathy compared with a group of control subjects without diabetes and of similar age and sex. METHODS: In samples obtained after vitrectomy for diabetic retinopathy in patients and for macular hole in control subjects, immunoblot techniques were applied to a mini-array system for quantification of a wide range of chemokines and vasoactive peptides and proteins. Antiphosphotyrosine antibody was used for tyrosine phosphorylation evaluation and results were expressed as the percentage of variation compared with that in control subjects. RESULTS: Samples from eight patients with type 2 diabetes and from eight control subjects were analyzed. The total quantity of proteins analyzed was similar in both patients and control subjects. Tyrosine phosphorylation was very significantly decreased (<20%, P < 0.05) in diabetic patients with respect to the control group in growth-related oncogene, human cytokine I-309, interleukin-13, monocyte colony-stimulating factor, macrophage-derived chemokine, stem cell factor, transforming growth factor-beta1, angiogenin, and oncostatin M. A significant decrease in phosphorylation (between 20% and 40%, P < 0.05) was observed in epithelial neutrophil-activating peptide 78; granulocyte colony-stimulating factor; granulocyte-monocyte-stimulating colony factor; IL-5, -6, -7, -8, -10, and -12p40p70; monokine induced by interferon-gamma; macrophage inflammatory protein 1-gamma; and normal T expressed and secreted cytokine (RANTES) in comparison with that in the control subjects. The greatest decrease in phosphorylation status was found in IL-1-alpha and -1beta. CONCLUSIONS: Diabetic retinopathy is associated with a decrease in tyrosine phosphorylation of many vitreous proteins which may indicate an alteration in protein functionality or action even before significant quantitative variations.