STREPTOCOCCUS SUIS ENDOGENOUS ENDOPHTHALMITIS IN A PATIENT WITH MENINGITIS.

BACKGROUND: Streptococcus suis is a major porcine pathogen that can cause severe systemic infection in humans. The common clinical features include meningitis, septicemia, purulent arthritis, and oftentimes deafness. However, ocular inflammation is very rare. METHODS: We report the case of endogenous endophthalmitis, meningitis, and septicemia caused by S. suis. The patient received 2 months of systemic antibiotics therapy, intravitreal vancomycin, and vitrectomy combining phacoemulsification with intraocular lens without silicone oil-filled. RESULTS: The result with the best-corrected visual acuity was 20/40 on the left eye and 20/25 on the right eye. CONCLUSION: This case illustrates the rare presentation of endogenous endophthalmitis in a patient with meningitis due to S. suis. In patients presenting with endophthalmitis and meningitis, S. suis should be considered, especially if prominent and early visual acuity impairment is present.

Effects of Diabetes on Microcirculation and Leukostasis in Retinal and Non-Ocular Tissues: Implications for Diabetic Retinopathy.

Changes in retinal microcirculation are associated with the development of diabetic retinopathy (DR). However, it is unclear whether such changes also develop in capillary beds of other non-retinal tissues. Here, we investigated microcirculatory changes involving velocity of rolling neutrophils, adherence of neutrophils, and leukostasis during development of retinal vascular lesions in diabetes in other non-retinal tissues. Intravital microscopy was performed on post-capillary venules of cremaster muscle and ear lobe of mice with severe or moderate diabetes and compared to those of non-diabetic mice. Additionally, number and velocity of rolling leukocytes, number of adherent leukocytes, and areas of leukostasis were quantified, and retinal capillary networks were examined for acellular capillaries (AC) and pericyte loss (PL), two prominent vascular lesions characteristic of DR. The number of adherent neutrophils and areas of leukostasis in the cremaster and ear lobe post-capillary venules of diabetic mice was increased compared to those of non-diabetic mice. Similarly, a significant increase in the number of rolling neutrophils and decrease in their rolling velocities compared to those of non-diabetic control mice were observed and severity of diabetes exacerbated these changes. Understanding diabetes-induced microcirculatory changes in cremaster and ear lobe may provide insight into retinal vascular lesion development in DR.

High Glucose Increases Binding of Lysyl Oxidase to Extracellular Matrix Proteins: Implications for Diabetic Retinopathy.

Purpose: To determine whether high glucose (HG) compromises internalization of lysyl oxidase (LOX) through excess binding of LOX with extracellular matrix (ECM) proteins. Methods: To determine whether HG promotes binding of LOX with ECM proteins, fibronectin (FN) and collagen IV (Coll IV), total or ECM-only proteins from rat retinal endothelial cells grown in normal (N; 5 mM) or HG (30 mM) medium were analyzed by coimmunoprecipitation and Western blot (WB). In parallel, coimmunostaining was performed to determine changes in LOX binding to FN or Coll IV. To determine the effect of HG on extracellular LOX levels, medium in which cells were grown for 1, 3, 5, and 7 days were assessed for LOX levels. Results: WB analysis using total protein showed LOX overexpression and elevated levels of LOX bound to Coll IV or FN in HG condition. Similarly, a significant increase in LOX bound to FN or Coll IV was observed in ECM-only protein. These data were supported by Z-stack confocal microscopy images from coimmunostaining. Furthermore, immunostaining performed on ECM layer revealed increased presence of LOX bound to Coll IV or FN. Additionally, when media from cells grown in HG was monitored, a maximal increase in LOX level was observed by day 3, which declined by day 7. Conclusions: Findings indicate that HG promotes binding of LOX to FN and Coll IV extracellularly that results in reduced LOX internalization, attenuation of negative feedback, and upregulation of LOX expression associated with diabetic retinopathy.

Decreased lysyl oxidase level protects against development of retinal vascular lesions in diabetic retinopathy.

Retinal capillary basement membrane (BM) thickening is closely associated with the development of vascular lesions in diabetic retinopathy. Thickened capillary BM can compromise blood-retinal-barrier characteristics and contribute to retinal vascular permeability, a significant clinical manifestation of diabetic retinopathy. We have previously shown that high glucose increases the expression and activity of lysyl oxidase (LOX), a crosslinking enzyme, in retinal endothelial cells. Additionally, concomitant with overexpression of LOX, increased vascular permeability was observed in diabetic rat retinas. However, it is unknown whether decreasing LOX overexpression may have protective effects against development of retinal vascular lesions in diabetes. To investigate whether reduced LOX level protects against diabetes-induced development of retinal vascular lesions characteristic of diabetic retinopathy, four groups of mice: wild type (WT) control mice, streptozotocin (STZ)-induced diabetic mice, LOX +/- mice, and STZ-induced diabetic LOX +/- mice were used for this study. Diabetes was maintained for 16 weeks; at the end of the study, retinas were assessed for LOX protein level by Western Blot (WB) analysis, and retinal capillary networks were isolated using retinal trypsin digestion and stained with hematoxylin and periodic acid Schiff to identify the number of acellular capillaries (AC) and pericyte loss (PL). In parallel, TUNEL assay was performed on retinal trypsin digests (RTDs) to detect cells undergoing apoptosis in the retinal capillary networks. Retinal vascular permeability was analyzed following FITC-dextran injection in retinal whole mounts. A significant increase in LOX expression was detected in the diabetic retinas compared to those of the WT control retinas, and as expected, a significant decrease in LOX expression in the diabetic LOX +/- retinas was observed compared to those of the diabetic retinas. RTD images showed significantly increased AC and PL counts in the retinas of diabetic mice compared to those of the WT control mice. Importantly, the number of AC and PL was significantly decreased, as was retinal vascular permeability in the retinas of the diabetic LOX +/- mice compared to those of the diabetic mice. Results suggest that decreasing diabetes-induced LOX overexpression may have protective effects against the development of vascular lesions characteristic of diabetic retinopathy. Therefore, LOX overexpression may be a potential target in preventing retinal vascular cell loss and excess permeability associated with diabetic retinopathy.

Inhibition of Diabetes-Induced Lysyl Oxidase Overexpression Prevents Retinal Vascular Lesions Associated With Diabetic Retinopathy.

Purpose: The purpose of this study was to investigate the effect of reducing diabetes-induced lysyl oxidase (LOX) overexpression on vascular cell apoptosis and blood-retinal barrier (BRB) characteristics in diabetic rats. Methods: Nondiabetic rats, diabetic rats, and diabetic rats intravitreally (IV) injected with LOX siRNA or scrambled (scram) siRNA were used in the study. One month after the onset of diabetes, intravitreal injections were initiated at monthly intervals for up to three times. At the end of study, retinal capillary networks were isolated, stained with periodic acid-Schiff (PAS) and hematoxylin, and assessed for acellular capillaries (AC) and pericyte loss (PL). To assess vascular leakage, extravasation of FITC-dextran was evaluated in retinal capillaries after tail vein injection of FITC-dextran. Western blot analysis was performed to determine retinal LOX level and confirm LOX downregulation via LOX siRNA intravitreal injection. Results: LOX expression was significantly upregulated in retinas of diabetic rats compared with that of nondiabetic rats. Diabetic rats injected with LOX siRNA showed a significant decrease in retinal LOX expression compared with those of diabetic rats or scram siRNA-injected rats. In diabetic retinas, AC and PL were significantly increased compared with those of nondiabetic retinas. Importantly, diabetic rats treated with LOX siRNA exhibited a significant decrease in AC and PL counts compared with those of untreated diabetic rats. Furthermore, diabetic rats treated with LOX siRNA showed significant decrease in retinal vascular permeability compared with that of untreated diabetic rats. Conclusions: Findings suggest LOX siRNA intravitreal injection may be effective against diabetes-induced LOX overexpression in preventing apoptosis and vascular leakage associated with diabetic retinopathy.