Angiogenin (ANG) is involved in the innate immune system and inflammatory disease. The aim of this study is to evaluate the anti-inflammatory effects of ANG in an endotoxin induced uveitis (EIU) rat model and the pathways involved. EIU rats were treated with balanced salt solution (BSS), a non-functional mutant ANG (mANG), or wild-type ANG (ANG). The integrity of the blood-aqueous barrier was evaluated by the infiltrating cell and protein concentrations in aqueous humor. Histopathology, Western blot, and real-time qRT-PCR of aqueous humor and ocular tissue were performed to analyze inflammatory cytokines and transcription factors. EIU treated with ANG had decreased inflammatory cells and protein concentrations in the anterior chamber. Compared to BSS and mANG, ANG treatment showed reduced expression of IL-1β, IL-8, TNF-α, and Myd88, while the expression of IL-4 and IL-10 was increased. Western blot of ANG treatment showed decreased expression of IL-6, inducible nitric oxide synthase (iNOS), IL-1β, TNF-α, and phosphorylated NF-κB and increased expression of IL-10. In conclusion, ANG seems to reduce effectively immune mediated inflammation in the EIU rat model by reducing the expression of proinflammatory cytokines, while increasing the expression of anti-inflammatory cytokines through pathways related to NF-κB. Therefore, ANG shows potential for effectively suppressing immune-inflammatory responses in vivo.

Hyperglycemia plays a key role in the development of microvascular complications, endothelial dysfunction (ED), and inflammation. It has been demonstrated that cathepsin S (CTSS) is activated in hyperglycemia and is involved in inducing the release of inflammatory cytokines. We hypothesized that blocking CTSS might alleviate the inflammatory responses and reduce the microvascular complications and angiogenesis in hyperglycemic conditions. In this study, we treated human umbilical vein endothelial cells (HUVECs) with high glucose (HG; 30 mM) to induce hyperglycemia and measured the expression of inflammatory cytokines. When treated with glucose, hyperosmolarity could be linked to cathepsin S expression; however, many have mentioned the high expression of CTSS. Thus, we made an effort to concentrate on the immunomodulatory role of the CTSS knockdown in high glucose conditions. We validated that the HG treatment upregulated the expression of inflammatory cytokines and CTSS in HUVEC. Further, siRNA treatment significantly downregulated CTSS expression along with inflammatory marker levels by inhibiting the nuclear factor-kappa B (NF-κB) mediated signaling pathway. In addition, CTSS silencing led to the decreased expression of vascular endothelial markers and downregulated angiogenic activity in HUVECs, which was confirmed by a tube formation experiment. Concurrently, siRNA treatment reduced the activation of complement proteins C3a and C5a in HUVECs under hyperglycemic conditions. These findings show that CTSS silencing significantly reduces hyperglycemia-induced vascular inflammation. Hence, CTSS may be a novel target for preventing diabetes-induced microvascular complications.

Purpose: To quantify the susceptibility of the deep capillary plexus (DCP) in comparison with that of the superficial capillary plexus (SCP) in eyes with branch retinal vein occlusion (BRVO) using swept-source optical coherence tomography angiography (SS-OCTA). Methods: SS-OCTA (Triton^TM; Topcon, Tokyo, Japan) scans (3 × 3 mm) of 41 patients with BRVO were retrospectively analyzed. The mean vessel densities (VDs) of the SCP and the DCP were calculated in eyes with BRVO using the ImageJ program (National Institutes of Health, Bethesda, MD, USA) and compared with those in the normal fellow eye without any morbidity or unaffected sector in the BRVO eye. Results: The reduction rate of mean VD in SCP and DCP between the affected and unaffected sector of eyes with BRVO was 13.88 and 24.60%, respectively. Additionally, the reduction rate of mean VD in the SCP and DCP in the affected sector of BRVO eyes versus the corresponding sector of fellow eyes was 13.31 and 24.49%, respectively. Conclusion: The DCP was 1.77–1.84 times more affected than the SCP by ischemic damage in eyes with BRVO.

To investigate quantitative changes in eyelid parameters after orbital decompression surgery in thyroid-associated orbitopathy using the PC-based program, Eyelid Analysis Software (EAS). This study included 202 eyes of 109 thyroid-associated orbitopathy patients. Digital photographs of the patients in primary gaze were taken just before and after orbital decompression surgery, and exophthalmos degree was measured by Hertel exophthalmometry (Hertel Exophthalmometer SKU:52400; Oculus, Arlington, VA, USA). The custom-made PC-based software EAS (Biomedical Research Institute, Seoul, Korea) was used to analyze eyelid parameters. The 11 parameters included pupil to inferior eyebrow distance (PBD), margin reflex distance 1 (MRD1), margin reflex distance 2 (MRD2), palpebral fissure (PF), total lid length, upper and lower lid length, area, medial area, center area, and lateral area. Univariate linear regression analysis showed a significant positive association between amount of exophthalmos reduction and the following parameters: area (p = 0.007); MRD2 (p = 0.043); upper lid length (p = 0.045); lower lid length (p = 0.006); medial area (p = 0.045); and lateral area (p = 0.005). Multivariate linear regression analysis showed only two parameters, lower lid length (p = 0.022) and lateral area (p = 0.019) were associated with exophthalmos reduction. A reduction in the inferior lateral part of the eyelid (lateral area + lower lid length) occurred after orbital decompression surgery in patients with thyroid-associated orbitopathy.

Kim JT, et al. J Korean Med Sci. 2016 May;31(5):783-789. https://doi.org/10.3346/jkms.2016.31.5.783