Efficiency of different imaging methods in detecting ocular foreign bodies.

BACKGROUND: Ocular foreign bodies (OFBs) are a relatively common occurrence in ocular injuries, and a severe risk factor for vision disorders. They are notoriously challenging to identify and localize precisely to allow surgical removal, even with the most recent technological advancements. PURPOSE: To compare the efficiency of different imaging methods in detecting and localizing OFBs. METHODS: We conducted a retrospective analysis of the medical records of patients with OFBs, detected by ultrasound biomicroscopy (UBM) and confirmed during surgery. Patients who presented to our medical center between January 2016 and January 2022 and also underwent computed tomography (CT), X ray, and/or ocular B-scan ultrasonography (B-scans) were selected. RESULTS: This study included 134 patients with a history of ocular trauma and OFBs (mean age: 47.25 years, range: 8-78). The mean time interval from injury to UBM examination was 36.31 months (range: 0.2-120 months). Most OFBs were metallic (51.82%) or plant-based (25.37%); 22.39% of them were located in the sclera, 26.87% in the anterior chamber, and 23.88% in the ciliary body and iris. OFBs ranged in size from 0.10 to 6.67 mm (mean: 1.15 ± 1.10 mm). B-scans identified OFBs in 37 of the 119 patients examined (31.09%); CT in 52 of 84 patients (61.90%); and radiography in 29 of 50 patients (58.00%). Univariate and multivariate analyses determined that both CT and radiography showed low detection rates for plant-based versus non-plant-based OFBs (CT: p < 0.001; radiography: p = 0.007), small particles (<1.00 mm vs. >1.00 mm; CT: p = 0.001, radiography: p = 0.024), and with eyeball wall locations (vs. intraocular; CT: p < 0.001, radiography: p = 0.021). Similarly, B-scans were less efficient for plant-based and eyeball wall-located OFBs (both p = 0.001), whereas the difference based on dimensions was not significant (p = 0.118). CONCLUSIONS: CT, radiography, and B-scans showed lower detection rates for plant-based, small, and eyeball wall-located OFBs. Our findings strongly suggest that UBM could be a more adequate imaging modality when such OFBs are suspected.

Serum amyloid A aggravates endotoxin-induced ocular inflammation through the regulation of retinal microglial activation.

Serum amyloid A (SAA) are major acute-phase response proteins which actively participate in many inflammatory diseases. This study was designed to explore the function of SAA in acute ocular inflammation and the underlying mechanism. We found that SAA3 was upregulated in endotoxin-induced uveitis (EIU) mouse model, and it was primarily expressed in microglia. Recombinant SAA protein augmented intraocular inflammation in EIU, while the inhibition of Saa3 by siRNA effectively alleviated the inflammatory responses and rescued the retina from EIU-induced structural and functional damage. Further study showed that the recombinant SAA protein activated microglia, causing characteristic morphological changes and driving them further to pro-inflammatory status. The downregulation of Saa3 halted the amoeboid change of microglia, reduced the secretion of pro-inflammatory factors, and increased the expression of tissue-reparative genes. SAA3 also regulated the autophagic activity of microglial cells. Finally, we showed that the above effect of SAA on microglial cells was at least partially mediated through the expression and signaling of Toll-like receptor 4 (TLR4). Collectively, our study suggested that microglial cell-expressed SAA could be a potential target in treating acute ocular inflammation.

Scleral Suture Intraocular Lens Fixation Under Microscope-Intraoperative Optical Coherence Tomography.

PURPOSE: The aim of this study was to evaluate the accessibility and potential value of intraoperative optical coherence tomography (iOCT) during scleral suture intraocular lens (IOL) fixation. METHODS: This was a prospective cohort study in the Department of Ophthalmology, Eye and ENT Hospital, Fudan University, China. Seven eyes with insufficient capsular support and undergoing two-point scleral suture IOL fixation were included. The potential value of iOCT was evaluated, as well as the safety and efficacy of the surgery. RESULTS: Seven eyes were included. With a tailor-made iOCT, the structure of the anterior segment could be clearly visualized during the surgery. Intraoperatively, iOCT helped locate the proper place for fixation and access the position of the IOL. After an average 4.43-month follow-up, the spherical equivalent changed significantly ( P < 0.001), but the intraocular pressure, best-corrected visual acuity, and endothelial cell density remained unchanged ( P > 0.05). The IOL was well-centered with a horizontal and a vertical tilt of 0.74 ± 0.60° and 1.13 ± 0.65°, and decentration of 0.28 ± 0.12 mm and 0.30 ± 0.13 mm. The estimated IOL-induced astigmatism was -0.11 diopters (D) ± 0.46 D. CONCLUSION: Real-time high-resolution images of the anterior segment acquired by the iOCT helped the surgeon to achieve satisfactory results in scleral suture IOL fixation.

Alpha 7-nicotinic cholinoceptor regulation of pericyte-containing retinal capillaries.

BACKGROUND AND PURPOSE: Local blood flow regulation relies on the coordination between neurons and pericyte-containing capillaries. Pericyte relaxation and contraction are influenced by vasoactive substances and regulated by neurotransmitters. α7 nicotinic acetylcholine receptors (α7-nAChRs), involved in the regulation of vascular function and inhibitory γ-aminobutyric acid (GABA) systems, have neuroprotective effects against CNS diseases. Although α7-nAChRs are found throughout the retina, their contribution to the retinal capillary tone remains unknown. Here, we investigated the neurovascular coupling mechanism underlying α7-nAChR-mediated retinal capillary tone regulation. EXPERIMENTAL APPROACH: Changes in capillary diameter and pericyte transverse diameter during drug perfusion were observed using differential interference contrast (DIC) microscopy, to help elucidate signalling pathways underlying α7-nAChR-mediated regulation of capillary blood flow at the whole retinal level. Patch clamp technique was used to investigate α7-nAChR-mediated regulation of the GABA synaptic circuit. Immunofluorescence was used to explore the expression of α7-nAChRs and GABA receptors. KEY RESULTS: Activating α7-nAChRs on the endothelial cell membrane caused perinuclear accumulation of endothelial nitric oxide synthase (eNOS), resulting in dilated retinal capillaries and pericytes via the nitric oxide synthase (NOS)/nitric oxide (NO)/guanosine 3',5'- monophosphate (cGMP) signalling pathway. Neuronal α7-nAChR activation directly relaxed retinal capillaries and pericytes via a neurovascular coupling mechanism. α7-nAChR also increased the vesicular release of GABA, possibly promoting the release of NO by binding to GABAA receptors in retinal ganglion cells (RGCs) and relaxing blood vessels via eNOS-NO, with GABA binding to GABAB receptors on retinal capillary endothelial cells. CONCLUSION AND IMPLICATIONS: α7-nAChR activation causes vasorelaxation of retinal capillaries.

Silicone oil residual after vitrectomy for rhegmatogenous retinal detachment.

OBJECTIVE: To explore the presence of residual emulsified silicone oil (SO) droplets in patients with rhegmatogenous retinal detachment (RRD) and their possible risk factors. METHODS: Patients who underwent primary pars plana vitrectomy with SO injection for RRD and SO removal at the same eye centre were included. Approximately 10 weeks after SO removal, B-scan ultrasonography was performed, and using ImageJ, the silicone oil index (SOI) was measured, and its possible correlations with other clinical factors were explored. RESULTS: A total of 101 eyes were included. Residual SO particles were found in all the patients (100%), and the mean SOI was 4.04% ± 5.16% (range 0.06%-19.88%). Multiple linear regression revealed that, among all the clinical factors, axial length (AL) and ocular hypertension (intraocular pressure (IOP) > 21 mmHg or the use of antiglaucoma medications) before SO removal were positively and significantly associated with the SOI (all P < 0.05). Patients with ocular hypertension after SO removal had a higher SOI, a longer SO duration, a higher IOP before SO removal and a longer AL than those without (all P < 0.05). CONCLUSIONS: Patients with a larger AL and higher IOP before SO removal were more prone to have more residual SO droplets, which might in turn lead to an elevated IOP. In these eyes, thorough irrigation or repeated fluid-air exchange might be necessary.

Extraction, Isolation and Characterization of Mycosporine-like Amino Acids from Four Species of Red Macroalgae.

Marine macroalgae is known to be a good source of mycosporine-like amino acids (MAAs), especially red macroalgae. As a new type of active substance with commercial development prospects, the current progress in the extraction, isolation and characterization of MAAs is far from sufficient in terms of effectiveness in application. To determine the extraction processes of MAAs from four species of red macroalgae (Bangia fusco-purpurea, Gelidium amansii, Gracilaria confervoides, and Gracilaria sp.), a series of single-factor and orthogonal experiments were carried out in which the effects of solvents, the solid-liquid ratio, the time of extraction, the extraction degree and the temperature, on the yields of MAA extracts, were analyzed. Further, the isolation and identification of MAAs from Bangia fusco-purpurea and Gracilaria sp. were investigated. The results showed that the solid-liquid ratio, the time of extraction, the extraction degree and the temperature were 1:20 g/mL, 2 h, three times and 40 °C, respectively, when 25% methanol or 25% ethanol were used as the extraction solvent; these values were found to be suitable for the extraction of MAAs from four species of red macroalgae. Silica gel thin-layer chromatography was successfully used, for the first time, for the detection MAAs in this work, and it could be clearly seen that Bangia fusco-purpurea had the highest contents of MAAs among the four species of red macroalgae. MAA extracts from Bangia fusco-purpurea (or Gracilaria sp.) were isolated by silica gel column chromatography to obtain one fraction (or two fractions). The compositions and proportions of the MAAs in these fractions were determined via HPLC-ESI-MS spectra and by comparison with existing studies. Shinorine, palythine and porphyra-334 were found in 95.4% of the T1 fraction, and palythenic acid was found in 4.6% of this fraction, while shinorine, palythine and porphyra-334 were found in 96.3% of the J1 fraction, palythenic acid was found in 3.7% of the J2 fraction, and palythine was found in 100% of the J2 fraction, taken from the MAA extracts found in Bangia fusco-purpurea and Gracilaria sp., respectively. In addition, the relevant compositions and proportions of the MAA extracts taken from Gelidium amansii and Gracilaria confervoides were identified. This was the first study to report on the extraction process, isolation and identification of MAAs from Bangia fusco-purpurea, Gelidium amansii, Gracilaria confervoides, and Gracilaria sp.

Triamcinolone acetonide-chitosan coated liposomes efficiently treated retinal edema as eye drops.

Macular edema (ME), which is present in various retinal diseases, leads to permanent retinal structural damage and threatens vision. The intravitreal/periocular injection of triamcinolone acetonide (TA) can improve the prognosis of ME; however, further exploration of noninvasive delivery systems is essential. Therefore, as a continuation of our previous study using TA-chitosan coated liposomes (TA-CHLs) as a topical drug delivery system, the present study aimed to determine the drug safety, stability, permeability, and bioavailability of TA-CHLs. The study was based on detecting the delivery of a fluorescent dye to the retina using optical coherence tomography angiography in rats. Marked cellular uptake was observed in cell lines. TA-CHL toxicity was investigated in cell culture. Clinical ocular safety was evaluated by measuring the corneal thickness and intraocular pressure. In preclinical studies on a laser-induced retinal edema rat model, the TA-CHL eye drops had dramatic therapeutic effect in remission of retinal edema over 10 days. These results demonstrated that TA-CHL was nontoxic and had good bioavailability in vitro and in vivo. The results of the present study indicated that this formulation could be an effective therapeutic approach and the TA-CHL eye drops may represent a new option for retinal diseases.

HMGA1 exacerbates tumor progression by activating miR-222 through PI3K/Akt/MMP-9 signaling pathway in uveal melanoma.

High-mobility group A1 (HMGA1), an architectural transcription factor, participates in different human tumors' biological progression. HMGA1 overexpression is associated with malignant cellular behavior in a wide range of cancers but the underlying mechanism remains poorly illuminated. In this study, we showed PI3K/Akt/MMP9 pathway activity could be positively regulated by HMGA1 using western blotting, real-time polymerase chain reaction (RT-PCR) and immunochemistry both in vitro (C918 and MUM-2B cell lines) and in vivo (xenograft mouse model). Later, MiRTarBase was used to identify the relationship between HMGA1 and miR-222-3p, we found miR-222 is positively regulated by HMGA1. Moreover, the proliferation and migration of UM cells significantly increased in the miR-222 mimics group and decreased in the miR-222 inhibitor group detected by the Annexin V-FITC apoptosis detection kit, CCK-8 and scratch wound-healing. The p-PI3K, p-Akt and MMP9 expressions were elevated in UM cells transfected with miR-222 mimics, and suppressed in the miR-222 inhibitor group. Together, our study highlights that HMGA1 acts as a pivotal regulator in UM tumor growth, proposing a critical viewpoint that HMGA1 expedites progression through the PI3K/Akt/MMP9 pathway and oncogenic miR-222 in UM.

A more efficient ocular delivery system of triamcinolone acetonide as eye drop to the posterior segment of the eye.

As a leading cause of vision impairment of the retina, macular edema (ME) has one of the highest clinical demands for treatment. Current treatment of ME relies heavily on invasive techniques resulting in complications and poor patient compliance. To enhance the efficiency of triamcinolone acetonide as eye drop to the posterior segment of the eye, we developed and characterized a novel formulation, namely, triamcinolone acetonide chitosan-coated liposomes (TA-CHL), prepared by the calcium acetate gradient method with some modifications. TA-CHL provided the mean particle size of 135.46 ± 4.49 nm and high entrapment efficiency (90.66 ± 3.21%), exhibited a sustained release profile, excellent physical stability, and no significant toxicity on cornea, conjunctiva, and retina. Optical coherence tomography system (OCT) was used to detect pharmacokinetics of CHL in vivo, indicating that CHL had good potency for drug delivery. Cellular uptake experiments showed CHL had the higher transduction efficiency into HCEC and ARPE-19 than liposomes. TA-CHL was shown to be potentially effective eye drop to contribute to the posterior segment of the eye.

TIMP-3 suppression induces choroidal neovascularization by moderating the polarization of macrophages in age-related macular degeneration.

PURPOSE: To investigate the role of tissue inhibitor of metalloproteinases-3 (TIMP-3) as a key moderator of macrophage polarization in choroidal neovascularization (CNV) lesions of model mice and in bone marrow-derived macrophage (BMDM). METHOD: We used siR-TIMP-3 to transfect BMDM and gave an intravitreal injection of siR-TIMP-3 to laser-induced CNV mice model, real time-PCR and western blot were applied for detecting the expressions of TIMP-3 and macrophages' biomarker. Besides, CNV lesions in different treatment groups of animal model were examined by the optical coherence tomography angiography (OCTA). RESULTS: Our experimental data showed that lack of TIMP-3 stimulated M2 polarization proved by real time-PCR and western blot in BMDMs and CNV mice model. Moreover, intravitreal injection of siR-TIMP-3 accelerated CNV formation using OCTA, which indicated that TIMP-3 suppression is related to pro-angiogenesis of M2 macrophage. CONCLUSION: We showed that the absence of TIMP-3 leads to a more pro-angiogenic microenvironment, playing a key role in CNV formation by positively modulating M2 polarization. The role of TIMP-3 in the regulating inflammation and novel therapeutic target of nAMD needs to be further studied.