Vitreous Humor Research Articles

Dietary Nitrate Metabolism in Porcine Ocular Tissues Determined Using 15N-Labeled Sodium Nitrate Supplementation.

Nitrate (NO3-) obtained from the diet is converted to nitrite (NO2-) and subsequently to nitric oxide (NO) within the body. Previously, we showed that porcine eye components contain substantial amounts of nitrate and nitrite that are similar to those in blood. Notably, cornea and sclera exhibited the capability to reduce nitrate to nitrite. To gain deeper insights into nitrate metabolism in porcine eyes, our current study involved feeding pigs either NaCl or Na15NO3 and assessing the levels of total and 15N-labeled NO3-/NO2- in various ocular tissues. Three hours after Na15NO3 ingestion, a marked increase in 15NO3- and 15NO2- was observed in all parts of the eye; in particular, the aqueous and vitreous humor showed a high 15NO3- enrichment (77.5 and 74.5%, respectively), similar to that of plasma (77.1%) and showed an even higher 15NO2- enrichment (39.9 and 35.3%, respectively) than that of plasma (19.8%). The total amounts of NO3- and NO2- exhibited patterns consistent with those observed in 15N analysis. Next, to investigate whether nitrate or nitrite accumulate proportionally after multiple nitrate treatments, we measured nitrate and nitrite contents after supplementing pigs with Na15NO3 for five consecutive days. In both 15N-labeled and total nitrate and nitrite analysis, we did not observe further accumulation of these ions after multiple treatments, compared to a single treatment. These findings suggest that dietary nitrate supplementation exerts a significant influence on nitrate and nitrite levels and potentially NO levels in the eye and opens up the possibility for the therapeutic use of dietary nitrate/nitrite to enhance or restore NO levels in ocular tissues.

Acanthosis nigricans - a potentially useful clue to the presence of significant occult disease at autopsy.

A 19-year-old male was found dead in his apartment. At autopsy he was morbidly obese (Body mass index; BMI - 40.5) with multiple areas of velvety pigmented thickening of the skin in folds around the neck, in the axillae, in the inframammary regions, over the anterior waistline and groin regions and over the dorsal aspects of the feet. These had the typical appearance of acanthosis nigricans. Internal examination revealed aspiration of gastric contents into the airways. Vitreous humour biochemistry showed markedly elevated levels of both glucose (62.9mmol/L) and β-hydroxybutyrate (13.54mmol/L). Death was, therefore, due to aspiration pneumonia complicating diabetic ketoacidosis on a background of morbid obesity. The initial indicator of underlying diabetes, in conjunction with obesity had been acanthosis nigricans.

TGFβ overcomes FGF-induced transinhibition of EGFR in lens cells to enable fibrotic secondary cataract.

To cause vision-disrupting fibrotic secondary cataract (PCO), lens epithelial cells that survive cataract surgery must migrate to the posterior of the lens capsule and differentiate into myofibroblasts. During this process, the cells become exposed to the FGF that diffuses out of the vitreous body. In normal development, such relatively high levels of FGF induce lens epithelial cells to differentiate into lens fiber cells. It has been a mystery as to how lens cells could instead undergo a mutually exclusive cell fate, namely epithelial to myofibroblast transition, in the FGF-rich environment of the posterior capsule. We and others have reported that the ability of TGFβ to induce lens cell fibrosis requires the activity of endogenous ErbBs. We show here that lens fiber-promoting levels of FGF induce desensitization of ErbB1 (EGFR) that involves its phosphorylation on threonine 669 mediated by both ERK and p38 activity. Transinhibition of ErbB1 by FGF is overcome by a time-dependent increase in ErbB1 levels induced by TGFβ, the activation of which is increased after cataract surgery. Our studies provide a rationale for why TGFβ upregulates ErbB1 in lens cells and further support the receptor as a therapeutic target for PCO.

"Not everything that can be counted counts" in ethanol toxicological results: an antemortem and postmortem technical interpretation focusing on driving under the influence.

Ethanol blood analysis is the most common request in forensic toxicology, and some studies point to positive results in approximately one-third of all unnatural deaths. However, distinguishing sober deaths from drunk deaths is not as simple as it may seem. This technical, clinical, and forensic interpretation is proposed to interpret the ethanol toxicological results, discussing several artefacts and pitfalls that must be considered, namely focusing on driving under the influence. This work is presented with a practical and objective approach, aiming to alleviate the complexities associated with clinical, physiological, pathophysiological, and toxicological aspects to enhance comprehension, practicality, and applicability of its content, especially to courts. Particularly the physical integrity of the body, the postmortem interval, putrefactive signs, anatomic place of blood collection, alternative samples such as vitreous humour and urine, the possibility of postmortem redistribution, the inclusion of preservatives in containers, and optimal temperature conditions of shipment are among some of the aspects to pay attention. Although several biomarkers related to postmortem microbial ethanol production have been proposed, their translation into forensic routine is slow to be implemented due to the uncertainties of their application and analytical difficulties. Specifically, in the interpretation of ethanol toxicological results, "not everything that can be counted counts and not everything that counts can be counted" (attributed to Albert Einstein).

A Case of Medical Malpractice; Misdiagnosis of Methamphetamine-related Cardiac Complications

Background: Professional neglect is a civil responsibility for any specialist or individual with a specific skill, including therapists, and is not limited to any particular profession. Case Presentation: A man 41-year-old drug abuser was diagnosed with a heart problem due to methamphetamine abuse. Despite his drug history, he was once admitted to the emergency room for chest pain, where acetaminophen and diazepam were prescribed. For the second time, he went to another medical center due to continued chest pain, and due to the suspicion of contracting COVID-19, a CT scan of the chest was performed, yielding negative results, and then he was discharged. The patient was found deceased in his bed the following day. An autopsy revealed a thinned heart wall, subendocardial hemorrhages, and severe atherosclerosis. Methamphetamine, amphetamine, and acetaminophen were detected in urine samples, and ethanol was detected in blood and vitreous humor samples. Conclusion: The case highlights the importance of medical negligence in treating patients with drug abuse.

Investigation of Differences in the Techniques of Experimental Vitreo-retinal Operations on Laboratory Animals

The continuous development of vitreoretinal surgery makes it possible to provide high-tech care to patients with retinal detachment while minimizing intraand postoperative complications. However, their percentage still remains significantly high. This pushes modern ophthalmological science to new research and search for solutions to existing problems. In this task, laboratory animals, on which the latest advances in medicine have been tested for more than 100 years, help like no one else. Unfortunately, the high cost of experiments often repels and/or pushes them back indefinitely. Given the clinical significance of experimental studies of surgical treatment of retinal detachment, as part of the study of the new hydrogel preparation Vitreolon, an analysis was made of methods for removing the vitreous body and their effect on the result of surgical intervention.Purpose: analysis of differences in vitreous removal techniques in laboratory rabbits.Material and methods. The experiment involved 6 rabbits (12 eyes) with induced retinal detachment. In 6 eyes, vitrectomy was performed using a vitreotome, in the others, using a syringe (21G). Subsequently, tamponade of the vitreal cavity was performed with the new hydrogel preparation “Vitreolon”. Ophthalmological examinations were performed on the 1st day, 1st and 2nd week, 1st and 3rd months after surgery. After that, the eyes were enucleated to conduct a morphological study of macropreparations and histological sections of the eyes.Results. According to the results of ophthalmological and laboratory studies, there was no statistically significant difference between the techniques for removing the vitreous body. One rabbit had hypertension and cataracts, which indicates its individual response to surgery. There were no complications that could lead to early termination of the experiment.

Clinical Features of Patients with Penetrating Eye Injury and Foreign Body Complicated by Endophthalmitis

Purpose: to study the clinical features of patients with penetrating eye injury and foreign body, complicated by endophthalmitis.Methods. 68 patients (68 eyes) with penetrating injury and ocular foreign body were included in the retrospective study, including 91.2 % males and 8.8 % females. The mean age was 50.00 [32.00; 60.00] years. The patients were divided into 2 groups: with endophthalmitis — 24 patients, without inflammation — 44 patients. All patients underwent standard ophthalmologic methods of examination.Results. The age of patients with endophthalmitis was significantly greater compared to patients without inflammation — 51.50 [46.25; 63.25] years and 36.50 [31.25; 58.50] years, respectively (p = 0.0446). In the first day after injury, only 25 % of patients asked for medical care (p = 0.0071). In patients with endophthalmitis according to biomicroscopy data on admission the following were significantly more frequent: eyelid edema (p < 0.0001), purulent discharge (p < 0.0001), total hyphema (p = 0.029), hypopyon (p < 0.0001), iris edema (p < 0.0001), fibrin in vitreous body (p = 0.0014), as well as its destruction (p = 0.0005). 87.5 % of patients with endophthalmitis showed absence of fundus reflex (p = 0.0105), and 25 % of patients with inflammation showed increased intraocular pressure (p = 0.0019). In patients with endophthalmitis, surgical treatment was performed: cataract phacoemulsification in 91.7 % of patients (p < 0.0001), vitreoectomy in 87.5 % (p = 0.0098), enucleation of the eye in 12.5 % (p = 0.0165) and evisceration in 12.5 % (p = 0.0165). Bacterial culture in patients with endophthalmitis revealed Gram-positive microflora in 100 % of cases. There were also significant differences between the groups in the intravitreal, systemic and subconjunctival antibiotic therapy used.Conclusion. Patients with penetrating eye injury and foreign body, complicated by endophthalmitis, are characterized by more signs of inflammation, pronounced damage to the eye and its structures.

Forward Light Scattering of the Vitreous Gel After Enzymatic Aging: An In Vitro Model to Study Vitreous Opacification.

Symptomatic vitreous opacifications, so-called floaters, are difficult to objectively assess majorly limiting the possibility of in vitro studies. Forward light scattering was found previously to be increased in eyes with symptomatic floaters. Using an objective setup to measure forward light scattering, we studied the effects of enzymatically digesting the components of the vitreous body on straylight to develop an in vitro model of vitreous opacifications. Fifty-seven porcine vitreous bodies were digested using hyaluronidase, collagenase, trypsin, and bromelain, as well as using a combination of hyaluronidase + collagenase and hyaluronidase + bromelain. A modified C-Quant setup was used to objectively assess forward light scattering. Depletion of hyaluronic acid majorly increased vitreous straylight (mean increase 34.4 deg2/sr; P = 0.01), whereas primarily digesting the vitreous gel with collagenase or trypsin did not significantly affect straylight. When collagenase or bromelain is applied in hyaluronic acid depleted vitreous gels, the increase in forward light scattering is reversed partially. The age-related loss of hyaluronic acid primarily drives the increase in vitreous gel straylight induced by conglomerates of collagen. This process can be reversed partially by digesting collagen. This in vitro model allows the objective quantification and statistical comparison of straylight burden caused by vitreous opacities and, thus, can serve as a first testing ground for pharmacological therapies, as demonstrated with bromelain.

Concentration units used to report blood- and breath-alcohol concentration for legal purposes differ between countries which is important to consider when blood/breath ratios of alcohol are compared and contrasted.

This technical note reviews the plethora of concentration units used to report blood-alcohol concentration (BAC) and breath-alcohol concentrations (BrAC) for legal purposes in different countries. The choice of units sometimes causes confusion when scientific papers originating from a certain country might be introduced into evidence via expert testimony, such as when alcohol-related crimes are prosecuted. The concentration units are also important to consider when blood/breath ratios (BBRs) of alcohol are calculated and compared between countries. Statutory BAC limits for driving in most nations are reported in mass/volume (m/v) units, such as g/100 mL (g%) in the United States, mg/100 mL (mg%) in the United Kingdom and Republic of Ireland, or g/L (mg/mL) in many EU nations. By contrast, Germany and the Nordic countries report BAC as mass/mass (m/m) units, hence g/kg or mg/g, which are ~5.5% lower than m/v units, because whole blood has an average density of 1.055 g/mL. There are historical reasons for reporting BAC in mass/mass units because the aliquots of blood analyzed were measured by weight rather than volume. The difference between m/m and m/v is also important in postmortem toxicology, such as when distribution ratios of ethanol between blood and other biological specimens, such as urine, vitreous humor, and cerebrospinal fluid, are reported.

In vivo evaluation of a Nano-enabled therapeutic vitreous substitute for the precise delivery of triamcinolone to the posterior segment of the eye

This study focused on the design of a thermoresponsive, nano-enabled vitreous substitute for the treatment of retinal diseases. Synthesis of a hydrogel composed of hyaluronic acid and a poloxamer blend was undertaken. Poly(D,L-lactide-co-glycolide) acid nanoparticles encapsulating triamcinolone acetonide (TA) were synthesised with a spherical morphology and mean diameter of ~ 153 nm. Hydrogel fabrication and nanoparticle loading within the hydrogel was confirmed via physicochemical analysis. Gelation studies indicated that hydrogels formed in nine minutes and 10 min for the unloaded and nanoparticle-loaded hydrogels, respectively. The hydrogels displayed in situ gel formation properties, and rheometric viscoelastic studies indicated the unloaded and loaded hydrogels to have modulus values similar to those of the natural vitreous at 37 °C. Administration of the hydrogels was possible via 26G needles allowing for clinical application and drug release of triamcinolone acetonide from the nanoparticle-loaded hydrogel, which provided sustained in vitro drug release over nine weeks. The hydrogels displayed minimal swelling, reaching equilibrium swelling within 12 h for the unloaded hydrogel, and eight hours for the nanoparticle-loaded hydrogel. Biodegradation in simulated vitreous humour with lysozyme showed < 20% degradation within nine weeks. Biocompatibility of both unloaded and loaded hydrogels was shown with mouse fibroblast and human retinal pigment epithelium cell lines. Lastly, a pilot in vivo study in a New Zealand White rabbit model displayed minimal toxicity with precise, localised drug release behaviour, and ocular TA levels maintained within the therapeutic window for the 28-day investigation period, which supports the potential applicability of the unloaded and nanoparticle-loaded hydrogels as vitreous substitutes that function as drug delivery systems following vitrectomy surgery.Graphical Fig. aSchematic representation of the nano-enabled therapeutic vitreous substitute synthesis process. This figure was partly generated using Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license

Расчет ИОЛ при комбинированной хирургии: факоэмульсификации катаракты и витрэктомии. Собственный опыт

At the present stage of development of ophthalmic surgical technique, indications for simultaneous cataract phacoemulsification and pars plana vitrectomy are constantly expanding, however, there is a problem of predicting refractive results, which is due to the difficulty of determining the effective position of the intraocular lens (IOL) in the eye without the presence of a vitreous body. Purpose. Assessment of the accuracy of the preoperative calculation of IOL in the eyes during combined surgery — cataract phacoemulsification and vitrectomy on the state of postoperative refraction. Material and methods. Combined surgery of cataract phacoemulsification and vitrectomy of pars plana with a caliber of 25 Gage was performed in 51 people (51 eyes) aged 70.4 ± 8.4 years. The calculation of IOL before surgery was carried out according to the data of a preoperative examination on an optical biometer IOL-Master-700 (Carl Zeiss, Germany), keratopography was performed on a rotary Scheimpflug camera (Oculus, Germany). The data on SRK-T with a range of more than 22.5 mm and Hoffer-Q with a range of less than 22.5 mm were used as a basis. Results. There were no complications during the operations and in the postoperative period. Preoperative uncorrected visual acuity (UCVA) was 0.21 ± 0.2 (0.05 to 0.8) and the best-corrected visual acuity (BCVA) was 0.44 ± 0.22 (from 0.1 to 0.9). The correction is from –9.0 D to +7.75 D (–0.61 ± 2.71 D). 6 months after the operation, the UCVA was 0.67 ± 0.22 (from 0.05 to 1.0), the BCVA was 0.9 ± 0.2 (from 0.3 to 1.0), respectively, while the correction was from –1.25 D to +1.0 D (–0.17 ± 0.94 D). The deviation from the expected refraction of the target at 1 week after surgery was ± 0.5 D, at 6 months after surgery ± 0.4 D, which turned out to be statistically insignificant (p &gt; 0.05). Conclusions. 1. Combined surgery phacoemulsification and vitrectomy in combination of cataracts with pathology of the vitreomacular interface, significantly increases visual acuity after surgery (by 0.43 ± 0.03, p &lt; 0.001). 2. Changes in clinical refraction during implantation of IOL based on hydrophobic acrylic in combined surgery are not statistically significant (an average shift of ± 0,4–0,5 D, p &gt; 0.05), which allows us to apply generally accepted formulas for calculating the effective position of IOL without using correction factors. Keywords: IOL calculation, cataract phacoemulsification, vitrectomy

Оценка эффективности антивазопролиферативной терапии у пациентов после хирургии субмакулярных кровоизлияний

Purpose. To evaluate the morphofunctional parameters of the retina after antagonists of Anti-vascular endothelial growth factor (anti-VEGF) therapy in patients with an active form of age-related macular degeneration (AMD) after minimally invasive surgical treatment of submacular hemorrhages (SMH). Material and methods. In a prospective study based on the Center of Ophthalmology of NMHC named after 85 people with an active form of AMD were included in Pirogov (Moscow). The average age of the patients was 71.3 ± 8.5 years, including 48 women aged 61 to 82 years and 37 men aged 74 to 78 years. Results. In this study, the choice of the “treat and extend” strategy is justified by a smaller number of intravitreal injections compared to a fixed one, which gives similar results of visual functions. Conclusion. Preservation of the vitreous body during vitreoretinal intervention allows you to adhere to the “treat and extend” mode without reducing the inter-injection interval. Keywords: submacular hemorrhage, tissue plasminogen activator, pneumodislocation

Комбинированный метод лечения рефрактерного диабетического макулярного отека

Purpose. To determine the effectiveness of the anatomical and functional results of treatment of refractory diabetic macular edema after removal of the inner limiting membrane using the latest generation anti-VEGF drug. Material and methods. We examined 6 patients with 1st type and 2nd type diabetes mellitus. The average age of the subjects was 47.45 ± 27.15 years. Of these, there were 4 women and 2 men. 1st type diabetes mellitus was detected in 2 people, in other patients — 2nd type. 3 patients had previously undergone pan-retinal photocoagulation (from 1st to 2nd stages). All patients received intravitreal injections (anti-VEGF) of Eylea (4–5 injections) during the last year. According to the optical coherence tomogram (OCT), macular edema was recorded, recurring on average after 1.36 ± 0.85 months. All patients underwent surgical treatment. In the presence of lens opacity, surgical treatment was started with phacoemulsification of cataracts. A microinvasive subtotal vitrectomy was performed with the removal of the posterior layers of the vitreous body and proliferative membranes fixed to the retina. The removal of the inner boundary membrane was performed after its staining in the size of two to three diameters of the optic disc without any tamponade. After 2 months, two patients had an increase in retinal thickness in the fovea. These patients received one injection of Vabismo. Results. The compared groups did not differ in morphofunctional characteristics. In the postoperative period, there was a tendency to increase visual acuity and decrease retinal thickness, regression of hard exudates in 4 patients. In 2 patients, an increase in retinal thickness in the fovea was noted after 2 months. After intravitreal injection of the latest generation anti-VEGF drug (Vabismo), these patients also showed an increase in visual acuity, regression of solid exudates and a decrease in retinal thickness. Conclusion. Microinvasive subtotal vitrectomy with removal of the inner limiting membrane in combination with intravitreal injection of the latest generation anti-VEGF drug (Vabismo) is an effective method of treating refractory diabetic macular edema. Keywords: anti-VEGF, Vabismo, diabetic macular edema, intravitreal injections, optical coherence tomogram, subtotal vitrectomy, inner boundary membrane

GnT-V-mediated aberrant N-glycosylation of TIMP-1 promotes diabetic retinopathy progression

BackgroundVascular endothelial growth factor (VEGF) signaling pathway plays an important role in the progression of diabetic retinopathy (DR). The glycosylation modification process of many key functional proteins in DR patients is abnormal. However, the potential involvement of abnormal N-glycoproteins in DR progression remains unclear.MethodsGlycoproteomic profiling of the vitreous humor was performed. The level of protein and N-glycoprotein was confirmed by Western blot and Lectin blot, respectively. The cell viability and migration efficiency were detected by CCK-8 and Transwell assay. Flow cytometry was conducted to analyze the level of cell apoptosis and reactive oxygen specie. Malondialdehyde, superoxide dismutase activity and VEGF content were detected by Enzyme linked immunosorbent assays. The interaction of metalloproteinase 1 (TIMP-1) with N-acetylglucosamine transferase V (GnT-V) was detected by GST pull-down. Hematoxylin and eosin staining and choroidal and retinal flat mount stained with fluorescein isothiocyanate-Dextran assay were used for functional research in vivo.ResultsWe found that N-glycosylation was up-regulated in DR rats and high glucose (HG)-induced human retinal pigment epithelium cell line ARPE-19. HG-induced inhibited the viability of ARPE-19 cells and promoted cell apoptosis and oxidative stress (OS), but these effects were reversed with kifunensine treatment, GnT-V knockdown and TIMP-1 mutation. Additionally, GnT-V binds to TIMP-1 to promote N-glycosylation of TIMP-1. Over-expression of GnT-V inhibited the viability of ARPE-19 cells and promoted cell apoptosis, OS and VEGF release, which these effects were reversed with TIMP-1 mutation. Interestingly, over-expression of GnT-V promoted retinal microvascular endothelial cells (RMECs) angiogenesis but was revered with TIMP-1 mutation, which was terminally boosted by VEGF-A treatment. Finally, knockdown of GnT-V relieved DR progression.ConclusionThe findings indicate that GnT-V can promote RMECs angiogenesis and ARPE-19 cells injury through activation VEGF signaling pathway by increasing TIMP-1 N-glycosylation level, which provides a new theoretical basis for the prevention of DR.

Assessment of intraocular pressure changes following intravitreal injections of three anti-VEGF agents

PurposeIntravitreal injection (IVI) of anti-vascular endothelial growth factor (anti-VEGF) agents has emerged as the primary treatment for prevalent retinal diseases. Despite its efficacy, IVI may induce intraocular pressure elevation due to vitreous fluid shifts. This study aims to compare the effects of three distinct anti-VEGF agents on intraocular pressure (IOP) elevation within a single clinic setting. DesignA prospective study, conducted at a single retinal clinic in a tertiary medical center (Tel Aviv Sourasky Medical Centre, Tel-Aviv, Israel). MethodsPatients receiving 3 different anti VEGF medications; bevacizumab, aflibercept, and ranibizumab, were examined. IOP was measured pre- and post-injection using an iCare Pro-tonometer. Demographic parameters and ocular characteristics were collected. ResultsThe study included 195 patients (average age 76.13 years; 100 males, 95 females). The medications administered were aflibercept (N = 70, 35 %), bevacizumab (N = 73, 37.4 %), and ranibizumab (N = 52, 26.7 %). In patients with a normal baseline intraocular pressure, no significant variance was observed in the post-injection versus pre-injection pressure change (delta) across medications. Conversely, in patients with higher pressure (>20 mmHg), aflibercept incited a more substantial increase than bevacizumab or ranibizumab. No correlation emerged between the pressure rise and age or lens status. ConclusionsNo significant difference was found in the increase of intraocular pressure following injection among different medications in patients with low-normal intraocular pressure. However, for patients prone to higher baseline pressure, caution is recommended with aflibercept due to a more pronounced increase. Further research is essential to comprehend the factors influencing pressure increase and their associated clinical implications.

Visual outcome of 25 Gauge vitrectomy for acute post operative infectious endophthalmitis.

The correlation between the change in foveal thickness measured using optical coherence tomography (OCT) following surgery for infectious endophthalmitis and preoperative and postoperative visual acuity is uncertain, and there are few pertinent studies on this topic. We explored the variations in macular thickness using OCT after emergency vitrectomy for post-cataract infectious endophthalmitis and the relationship between macular thickness with changes in visual function. We included 10 cases of post-cataract infectious endophthalmitis. Each patient underwent 25-G vitrectomy. The infection in all 10 patients was under control and visual function improved. Postoperative vitreous humor culture was positive in 8 patients, including 7 cases of coagulase-negative Staphylococcus epidermidis and 1 case of Lactobacillus acidophilus. The average age of these 10 patients was 71.60 ± 8.71 years (P< 0.05, two-tailed). There was no significant correlation between time 2 (the time of onset after cataract surgery) and visual prognosis. The average time 1 (the time of the vitrification surgery caused by the onset of the disease) was 1.45 ± 0.76 days (P< 0.05, two-tailed). The postoperative 3dVA ranged from 0.20 to 3.00, with an average visual acuity of 1.87 ± 1.12, which was superior to the preoperative value (P< 0.01, two-tailed). The correlation between the post3dVA and post 1mVA was significant. The post 1mVA ranged from 0.05 to 2.20, with an average visual acuity of 0.94 ± 0.74 (P< 0.05, two-tailed). The correlation between post 1mVA and post3mVA was significant. Also, paired t-tests comparing preoperative and postoperative visual acuity revealed a significant correlation (P< 0.05, two-tailed). The post3mVA was 0-1.00 with an average visual acuity of 0.44 ± 0.41. The postoperative foveal thickness ranged from 176.00 to 514.00 μm, with an average thickness of 281.10 ± 113.12 μm. Emergency 25-G minimally invasive vitrectomy can improve visual acuity and decrease the reoperation rate for patients who have acquired post-cataract infectious endophthalmitis. There were significant correlations between age, disease onset to operation time, preoperative and postoperative visual acuity, and postoperative macular thickness.

Retinal detachment.

Retinal detachment (RD) occurs when the neurosensory retina, the neurovascular tissue responsible for phototransduction, is separated from the underlying retinal pigment epithelium (RPE). Given the importance of the RPE for optimal retinal function, RD invariably leads to decreased vision. There are three main types of RD: rhegmatogenous, tractional and exudative (also termed serous) RD. In rhegmatogenous RD, one or more retinal breaks enable vitreous fluid to enter the subretinal space and separate the neurosensory retina from the RPE. In tractional RD, preretinal, intraretinal or subretinal membranes contract and exert tangential forces and elevate the retina from the underlying RPE. Finally, in exudative RD, an underlying inflammatory condition, vascular abnormality or the presence of a tumour causes exudative fluid to accumulate in the subretinal space, exceeding the osmotic pump function of the RPE. The surgical management of RD usually involves pars plana vitrectomy, scleral buckling or pneumatic retinopexy. The approach taken often depends on patient characteristics as well as on practitioner experience and clinical judgement. Advances in surgical technology and continued innovation have improved outcomes for many patients. However, even if retinal re-attachment is achieved, some patients still experience decreased vision or other visual symptoms, such as metamorphopsia, that diminish their quality of life. Continued research in the areas of neuroprotection and retinal biology as well as continued surgical innovation are necessary to enhance therapeutic options and outcomes for these patients.

In vitro and in vivo characterization of human serum albumin-based PEGylated nanoparticles for BDNF and NT3 codelivery

The utilization of neurotrophins in medicine shows significant potential for addressing neurodegenerative conditions, such as age-related macular degeneration (AMD). However, the therapeutic use of neurotrophins has been restricted due to their short half-life. Here, we aimed to synthesize PEGylated nanoparticles based on electrostatic-driven interactions between human serum albumin (HSA), a carrier for adsorption; neurotrophin-3 (NT3); and brain-derived neurotrophic factor (BDNF). Electrophoretic (ELS) and multi-angle dynamic light scattering (MADLS) revealed that the PEGylated HSA-NT3-BDNF nanoparticles ranged from 10 to 430 nm in diameter and exhibited a low polydispersity index (<0.4) and a zeta potential of −8 mV. Based on microscale thermophoresis (MST), the estimated dissociation constant (Kd) from the HSA molecule of BDNF was 1.6 μM, and the Kd of NT3 was 732 μM. The nanoparticles were nontoxic toward ARPE-19 and L-929 cells in vitro and efficiently delivered BDNF and NT3. Based on the biodistribution of neurotrophins after intravitreal injection into BALB/c mice, both nanoparticles were gradually released in the mouse vitreous body within 28 days. PEGylated HSA-NT3-BDNF nanoparticles stabilize neurotrophins and maintain this characteristic in vivo. Thus, given the simplicity of the system, the nanoparticles may enhance the treatment of a variety of neurological disorders in the future.

Comprehensive ocular and systemic pharmacokinetics of dexamethasone after subconjunctival and intravenous injections in rabbits

Even though subconjunctival injections are used in clinics, their quantitative pharmacokinetics has not been studied systematically. For this purpose, we evaluated the ocular and plasma pharmacokinetics of subconjunctival dexamethasone in rabbits. Intravenous injection was also given to enable a better understanding of the systemic pharmacokinetics. Dexamethasone concentrations in plasma (after subconjunctival and intravenous injections) and four ocular tissues (iris-ciliary body, aqueous humour, neural retina and vitreous) were analysed using LC-MS/MS.Population pharmacokinetic modelling for plasma data from both injection routes were used, and for first time the constant rate of absorption of dexamethasone from the subconjunctival space into plasma was estimated (ka,plasma = 0.043 min−1, i.e. absorption half-life of 17.3 min). Non-compartmental analysis was used for the ocular data analysis and resulting in ocular drug exposure of iris-ciliary body (AUC0-∞= 41984 min·ng/g) > neural retina (AUC0-∞= 25511 min·ng/g) > vitreous (AUC0-∞= 7319 min·ng/mL) > aqueous humour (AUC0-∞= 6146 min·ng/mL). The absolute bioavailability values after subconjunctival injection, reported for the first time, were 0.74 % in aqueous humour (comparable to topical dexamethasone suspensions), and 0.30 % in vitreous humour (estimated to be higher than in topical administration).These novel and comprehensive pharmacokinetic data provide valuable information on the potential for exploiting this route in ocular drug development for treating both, anterior and posterior segment ocular diseases. Moreover, the new generated dexamethasone-parameters are a step-forward in building predictive pharmacokinetic models to support the design of new subconjunctival dexamethasone formulations, which may sustain drug effect for longer period of time.

ABCA4 mediated traumatic proliferative vitreoretinopathy associated with PI3K/Akt signaling pathway

BackgroundProliferative vitreoretinopathy (PVR) is the main cause of retinal detachment. However, the underlying mechanism of PVR is complex and has not yet been fully elucidated. The PI3K/Akt/mTOR signaling pathway is involved in angiogenesis and plays an important role in cell proliferation and tumor formation. Therefore, our study was designed to investigate the potential biological mechanisms of alleviating ARPE-19 cell and traumatic PVR model involving PI3K/Akt signaling pathway by targeting ABCA4. Materials and methodsARPE-19 cell model was induced by ABCA4 overexpression vector and si-ABCA4, then the ABCA4 overexpression vector and si-ABCA4 were constructed, the plasmids were expanded for cell transfection and verification. In addition, OE-ABCA4, shRNA NC and si-ABCA4 were transfected into ARPE-19 cells. Cell viability was detected by CCK-8 assay, cell cycle was determined by flow cytometry. The expression level and location of ABCA4 were detected by immunofluorescence. Finally, rabbit traumatic PVR model was induced by surgery, the adenovirus was injected into the vitreous body respectively, and the fundus observation was performed by direct ophthalmoscope observation combined with fundus photography, and the retinal routine histopathology HE staining was performed. Analysis of P21, CDK4, Cyclin D1, BAX, BAD, and ABCA4 was used by quantitative RT-PCR and Western blot. Besides, the expression level of ABCA4, AKT, p-AKT, PI3K, p-PI3K, P38, p-P38, JNK, p-JNK, ERK, and p-ERK was detected by Western blot. ResultsAll results indicated that the viability of cells with high expression of ABC4A increased, while the viability of cells with inhibition of ABC4A decreased, the number of cells with high ABC4A expression was significantly higher, and the migration level of cells was significantly reduced after ABC4A inhibition (P < 0.05). ABC4A could affect cell apoptosis by affecting G1/G2 phase. The cell proliferation level was significantly increased with high expression of ABC4A. High expression of ABC4A increased phosphorylation levels, including p-AKT, p-PIK3, and p-P38, while inhibition of ABC4A decreased the expression levels of these proteins (P < 0.05). Inhibition of ABC4A could significantly improve retinopathy, indicating that the proliferation ability of cells was restored after inhibition of ABC4A. ConclusionsOur finding suggested that inhibition of ABC4A ameliorated the injury degree of traumatic PVR and performed the potential anti-PVR effect via inhibiting PI3K/Akt signaling pathway, while promoting cell proliferation in both rabbit and ARPE-19 cells PVR model. The study has a certain innovation by building a traumatic PVR model to explore whether the ABCA4 participates in the regulation of the PI3K/AKT signaling pathway and the pathological mechanism of PVR regulation. At the same time, ABCA4's participation in the regulation of PI3K/Akt signaling pathway can prevent and delay the occurrence and development of PVR, which has positive significance for improving the survival rate and quality of life of patients, and also provides an important basis for its therapeutic mechanism. Therefore, our study demonstrated a significant strategy for inhibiting traumatic PVR via targeting PI3K/Akt/ABCA4 pathway.