Engineering Matrix-Free Drug Protein Nanoparticles with Promising Penetration through Biobarriers for Treating Corneal Neovascularization.

Protein drugs have been widely used in treating various clinical diseases because of their high specificity, fewer side effects, and favorable therapeutic effect, but they greatly suffer from their weak permeability through tissue barriers, high sensitivity to microenvironments, degradation by proteases, and rapid clearance by the immune system. Herein, we disrupted the standard protocol where protein drugs must be delivered as the cargo via a delivery system and innovatively developed a free entrapping matrix strategy by simply mixing bevacizumab (Beva) with zinc ions to generate Beva-NPs (Beva-Zn2+), where Beva is coordinatively cross-linked by zinc ions with a loading efficiency as high as 99.2% ± 0.41%. This strategy was universal to generating various protein NPs, with different metal ions (Cu2+, Fe3+, Mg2+, Sr2+). The synthetic conditions of Beva-NPs were optimized, and the generated mechanism was investigated in detail. The entrapment, releasing profile, and the bioactivities of released Beva were thoroughly studied. By using in situ doping of the fourth-generation polyamindoamine dendrimer (G4), the Beva-G4-NPs exhibited extended ocular retention and penetration through biobarriers in the anterior segment through transcellular and paracellular pathways, effectively inhibiting corneal neovascularization (CNV) from 91.6 ± 2.03% to 13.5 ± 1.87% in a rat model of CNV. This study contributes to engineering of protein NPs by using a facile strategy for overcoming the weaknesses of protein drugs and protein NPs, such as weak tissue barrier permeability, low encapsulation efficiency, poor loading capacity, and susceptibility to inactivation.

LIN28A attenuates high glucose-induced retinal pigmented epithelium injury through activating SIRT1-dependent autophagy.

AIM: To evaluate the effects of LIN28A (human) on high glucose-induced retinal pigmented epithelium (RPE) cell injury and its possible mechanism. METHODS: Diabetic retinopathy model was generated following 48h of exposure to 30 mmol/L high glucose (HG) in ARPE-19 cells. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot tested the expression of the corresponding genes and proteins. Cell viability as well as apoptosis was determined through cell counting kit-8 (CCK-8) and flow cytometry assays. Immunofluorescence assay was adopted to evaluate autophagy activity. Caspase 3 activity, oxidative stress markers, and cytokines were appraised adopting their commercial kits, respectively. Finally, ARPE-19 cells were preincubated with EX527, a Sirtuin 1 (SIRT1) inhibitor, prior to HG stimulation to validate the regulatory mechanism. RESULTS: LIN28A was downregulated in HG-challenged ARPE-19 cells. LIN28A overexpression greatly inhibited HG-induced ARPE-19 cell viability loss, apoptosis, oxidative damage as well as inflammatory response. Meanwhile, the repressed autophagy and SIRT1 in ARPE-19 cells challenged with HG were elevated after LIN28A overexpression. In addition, treatment of EX527 greatly inhibited the activated autophagy following LIN28A overexpression and partly abolished the protective role of LIN28A against HG-elicited apoptosis, oxidative damage as well as inflammation in ARPE-19 cells. CONCLUSION: LIN28A exerts a protective role against HG-elicited RPE oxidative damage, inflammation, as well as apoptosis via regulating SIRT1/autophagy.

Clinical Comparative Study of Intravitreal Injection of Triamcinolone Acetonide and Aflibercept in the Treatment of Diabetic Retinopathy Cystoid Macular Edema.

Objective To compare the curative effect of intravitreal injection of triamcinolone acetonide and aflibercept on diabetic retinopathy (DR) cystoid macular edema. Methods A total of 102 patients with DR cystoid macular edema admitted to the hospital were enrolled between July 2018 and July 2021. According to random number table method, they were divided into the control group (intravitreal injection of triamcinolone acetonide) and the observation group (intravitreal injection of aflibercept), 51 cases in each group. All were followed up for half a year. The clinical curative effect, visual acuity, central subfield macular thickness (CSMT), macular volume, scores of quality of life, and levels of cytokines in aqueous humor (vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), human angiopoietin-like protein 4 (ANGPTL4)] at different time points (before and at 6 months after surgery) were compared between the two groups. The times of drugs injection and occurrence of adverse reactions in both groups were statistically analyzed. Results The total effective rate in observation group was higher than that in the control group (96.08% vs 82.35%) (P < 0.05). After 6 months of treatment, visual acuity was improved, and CSMT and macular volume were decreased in both groups. Also, the above changes were more significant in the observation group than those in the control group (P < 0.05). After 6 months of treatment, levels of cytokines in aqueous humor were decreased in both groups. The levels of VEGF, MCP-1, and ANGPTL4 in observation group were lower than those in the control group (P < 0.05). After 6 months of treatment, quality of life scores in observation group were higher than those in the control group (P < 0.05). In the follow-up period, average times of drugs injection in the observation group were more than those in the control group, and the incidence of adverse reactions was lower than that in control group (5.88% vs 21.57%) (P < 0.05). Conclusion The curative effect of intravitreal injection of both triamcinolone acetonide and aflibercept is good on DR cystoid macular edema. The curative effect of aflibercept is better, which can improve visual acuity and quality of life, and regulate cytokines in aqueous humor, with high safety. However, aflibercept has a high price, and further research is needed to determine whether its price can be matched with clinical benefits. In clinic, medication plan should be selected according to the actual situation.

Relationship between the 24-h variability of blood pressure, ocular perfusion pressure, intraocular pressure, and visual field defect in thyroid associated orbitopathy.

PURPOSE: To evaluate the relationship between the 24-h variability of blood pressure (BP), ocular perfusion pressure (OPP), intraocular pressure (IOP), and visual field (VF) defect in thyroid-associated orbitopathy (TAO). METHODS: Thirty patients (60 eyes) with TAO were clinically examined in the Eye Hospital of Wenzhou Medical University. Patients were divided into two groups: one with VF defect (A) and the other without (B). Clinical parameters measured include 24-h IOP, 24-h blood pressure, orbital computed tomography (CT) scan, optical coherence tomography (OCT), and VFs. The pulse pressure (PP), mean arterial pressure (MAP), mean ocular perfusion pressure (MOPP), and 24-h fluctuations were calculated by formula. RESULTS: The MOPP and MAP fluctuation were greater in group A than B (p < 0.05) and had significant negative correlation to mean deviation (MD) of VF (R = - 0.434 P = 0.001*). There was no statistical difference in the muscle index, medial rectus muscle thickness, and blood pressure between two groups. Although there were no significant differences in the mean IOP and IOP fluctuation between two groups, the incidence of IOP abnormalities has higher trend in group A. Patients with 24-h IOP fluctuation ≥8 mmHg and the mean IOP > 21 mmHg in the group A were more than group B. CONCLUSIONS: Dysthyroid optic neuropathy (DON) might have multiple pathogenic mechanisms. In this study, 24-h MOPP fluctuation and medial rectus maximal diameter were all the risk factors for DON. Higher mean IOP and 24-h IOP fluctuation might be risk factors for DON.

A New Way of Managing Canalicular Injury Associated With Late Eyelid Burns.

PURPOSE: This study aimed to introduce a new way to rebuild the canalicular system of patients with occluded punctums after long-time burns. METHODS: Cases with eyelid burns associated canalicular injury presented at Eye Hospital of Wenzhou Medical University from June 1st, 2015 to September 30th 2017 were referred to department of Orbital & Oculoplastic Surgery. Cases with occluded both superior and inferior punctuns were recommended to surgery. Twenty-seven cases were enrolled in our study. Patients were followed up at 1, 2, and 4 weeks and 3, 4, 6, and 12 months postoperatively. Success of the surgery was defined as being free of epiphora and purulence postoperatively, a normal functional endoscopic dye test, free-flowing irrigation through the lacrimal system, and the presence of upper and lower punctum ostium. RESULTS: With a follow-up of 12 months postoperative, there were 22 cases that showed surgical success outcome according to the set criteria. The success rate of our surgery is 81.48%. CONCLUSION: The surgical procedure used in our study is an effective and easy way to treat patiens with occluded punctum after long-time burns. The utility of silicone intubation is necessary and delayed tubing removal maybe meaningful in these kinds of patients.

Prognostic factors of trans-ethmosphenoid optic canal decompression for indirect traumatic optic neuropathy.

AIM: To investigate a possible correlation between visual acuity (VA) prognosis and the presence at baseline of various orbital and ocular signs in patients affected by indirect traumatic optic neuropathy (ITON). METHODS: From July 1st, 2012 to July 1st, 2015, 224 adults diagnosed with ITON who underwent endoscopic trans-ethmosphenoid optic canal decompression (ETOCD) were reviewed. Visual outcome before and after treatment were taken into comparison. RESULTS: Accompanied older in age, longer time to medical treatment and existence of optic canal fracture (OCF) were the independent predictors for poor postoperative VA and lower improvement degree of visual acuity (IDVA), while worse preoperative VA was predictive factor for poor postoperative VA only. Mean value of IDVA in patients with OCF was 0.19±0.30. Mean value of IDVA in patients without OCF was 0.29±0.35. IDVA in cases without OCF was significant higher than those with OCF (t=2.272, P<0.05). CONCLUSION: Patients suffered from ITON without OCF before ETOCD have better surgical outcome than those with OCF. Older in age, longer time to medical treatment and existence of OCF are independent factors for poor VA prognosis and lower IDVA. Preoperative VA is independent factor for VA prognosis only.