Exosomes from bone marrow-derived mesenchymal stem cells facilitate corneal wound healing via regulating the p44/42 MAPK pathway.

PURPOSE: This study was aimed at exploring the function of Exosomes isolated from bone marrow-derived mesenchymal stem cells (BMSC-Exos) in corneal wound healing and at revealing the underlying mechanisms involving the p44/42 mitogen-activated protein kinase (MAPK) pathway. METHODS: The isolated BMSC-Exos were identified by transmission electron microscopy, Western blot, and nanoparticle tracking analysis. After coculture with BMSC-Exos, the proliferation and migration of human corneal epithelial cells (HCEs) were evaluated. The protein expression of p-MEK/MEK and p44/42 MAPK was detected by Western blot. A mouse model of alkali-burned cornea was established via NaOH exposure. After injection with BMSC-Exos, the pathological changes and expression of α-SMA (a fibrosis marker) and CD31 (a vascularization marker) in corneal tissues were detected. RESULTS: BMSC-Exos enhanced the proliferation and migration of HCEs in a dose-dependent manner. The p44/42 MAPK pathway was activated by the treatment of BMSC-Exos, and its blocking using U0126 partially abrogated the effects of BMSC-Exos on promoting the proliferation and migration of HCEs. In vivo, the injection of BMSC-Exos facilitated the remission of the pathological changes (inflammation) and weakened the upregulation of α-SMA (fibrosis) and CD31 (vascularization) in corneal tissues of mice with alkali-burn injury. CONCLUSION: BMSC-Exos promoted the proliferation and migration of HCEs via activating the p44/42 MAPK pathway in vitro and also inhibited alkali burn-induced inflammation, fibrosis, and vascularization in corneal tissues in vivo. BMSC-Exos may be promising resources for promoting corneal wound healing.

The association of demodex infestation with pediatric chalazia.

PURPOSE: This study aimed to investigate the association of Demodex infestation with pediatric chalazia. METHODS: In a prospective study, 446 children with chalazia and 50 children with non-inflammatory eye disease (controls) who underwent surgical treatment were enrolled from December 2018 to December 2019. Patient ages ranged from 7 months to 13 years old. All patients underwent eyelash sampling for light microscope examination, and statistical correlation analysis between Demodex infestation and chalazia, including the occurrence, recurrence, and course of disease, morphological characteristics, and meibomian gland dysfunction (MGD) in chalazia patients was performed. RESULTS: Demodex was found in 236 (52.91%) patients with chalazia and zero control patients. Demodicosis was significantly more prevalent in chalazia patients than the control group (P < 1 × 10- 14). Recurrent chalazia (P = 0.006) and skin surface involvement (P = 0.029) were highly correlated with Demodex infestation. Demodicosis was also associated with multiple chalazia (P = .023) and MGD(P = .024). However, Demodex infestation was comparable in the course of disease (P = 0.15), seasonal change (P = 0.68) and blepharitis subgroups (P = 0.15). Within the group of chalazia patients who underwent surgical removal of cysts, 4 (0.9%) patients with concurrent demodicosis experienced recurrence. CONCLUSIONS: Demodex infestation was more prevalent in pediatric chalazia patients than healthy children, and was associated with recurrent and multiple chalazia. Demodicosis should be considered as a risk factor of chalazia. In children with chalazia, Demodex examination and comprehensive treatment of Demodex mites should be applied to potentially prevent recurrence.

[Effects of pericytes on the leakage of rat corneal neovascularization].

OBJECTIVE: To explore the effects of pericytes on the leakage of rat corneal neovascularization (CNV). METHODS: CNV was induced by micropocket assay in rats. Two eyes of the same rat were divided randomly into experimental and control groups. The experimental group received the VEGF + anti-PDGF-B pellet while the control group the VEGF + PBS pellet. Corneal samples were excised at Day 5 postoperation. CNV leakage was measured by Evans blue method. Pericyte coverage index (MPI) was applied to quantify the pericyte coverage through double immunofluorescent stain of frozen sections of corneas with CD31 as endothelial and α-smooth muscle actin (α-SMA) as pericyte marker. Corneal weight was measured. RESULTS: In the control group, MPI was 56.5%, cornea weight (7.36 ± 0.56) mg and CNV permeability rate (0.24 ± 0.07) µg×ml(-1)×mm(-2). In the experimental group, MPI was 11.3%, cornea weight (8.96 ± 1.09) mg and CNV permeability rate (0.68 ± 0.36) µg×ml(-1)×mm(-2). The intergroup difference was statistically significant (P MPI<0.01, P permeability= 0.01, P weight = 0.01). CONCLUSION: Pericytes inhibit the leakage of rat CNV. Such findings may guide the clinical management of hyperpermeability.

[Preparation and quality evaluation of ginkgolide B-loaded self microemulsifying drug delivery system].

OBJECTIVE: To prepare ginkgolide B-loaded self microemulsifying drug delivery system (SMEDDS) and evaluate its quality. METHOD: The solubility of ginkgolide B in different oil, surfactant and co-surfactant were measured by HPLC-ESI-MS. The GB-SMEDDS formulation was optimized by the self emulsifying efficiency of various combinations of oil and mix-surfactant evaluated by using pseudo-temary phase diagram. The preliminary stability of GB-SEMEDDS was evaluated by the variety of loading rate of GB and dispersed medium. The morphology, the particle size and the formulation stability were evaluated after diluting by 0.1 mol x L(-1) HCl. RESULT: The blank self microemulsified system was composed of ethyl oleate-( cremophor EL-lecithin-ethanol, 4: 1:2) (40: 60), the loading dosage was 2.5%. Little influence of GB and emulsified medium was observed on the stability of GB-SEMDDS. After diluted with 0.1 mol x L(-1) HCl, the morphology of the microemulsion was homogeneous small spherical drops observed under electro-microscope. The particle size was (41.6 +/- 1.11) nm, the self microemulsifing time was around 2 min. The formulation was stable within 8 h, without significant changes in particle size and separation of drugs. CONCLUSION: GB-SMEDDS is easy to prepare and its quality is stable. The solubility of GB was significantly improved by SMEDDS.

[A preliminary study on intravitreal injection of bevacizumab for treatment of neovascular age-related macular degeneration].

OBJECTIVE: To evaluate the short-term safety of intravitreous bevacizumab (Avastin) and its effects on visual acuity (VA) and subfoveal choroidal neovascularization (CNV) in patients with neovascular age-related macular degeneration (ARMD). METHODS: Single-center, uncontrolled clinical study. Five ARMD patients (5 eyes) with subfoveal CNV and best-corrected VA (BCVA) less than 0.1 were participated. Patients were treated with an intravitreous injection of bevacizumab (1.5 mg, 0.06 ml). Ophthalmologic evaluations included BCVA test, ocular examination, intraocular pressure (IOP) measurement, optical coherence tomography (OCT) imaging and fluorescein angiography (FFA). RESULTS: There were no ocular or systemic adverse events observed, except a mild elevation of IOP [26 mm Hg (1 mm Hg = 0.133 kPa)] in 1 case on the 3rd day after injection, which was controlled by topical medication. One out of 5 eyes had a significant improvement of BCVA (from 0.1 improved to 0.4) in one week after injection. By 2 months, the BCVA increased in 4 cases (increased 1 to 6 lines) and 3 of them remained stable for 4 to 6 months and 1 decreased at the 4 th month post injection. The thickness of central retina reduced 5.9% to 41.4% and FFA revealed a remarkable reduction or an absence of leakage from CNV in 3 eyes by the 4th month. CONCLUSION: Our preliminary results are promising, showing that intravitreous bevacizumab therapy is well tolerated with an improvement in VA, OCT, and FFA outcomes. A multi-center randomized controlled clinical trial is needed to evaluate the long-term safety and effectiveness of intravitreous bevacizumab therapy on neovascular ARMD.

Effects of melatonin in age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of severe visual loss in aged people. Melatonin has been shown to have the capacity to control eye pigmentation and thereby regulate the amount of light reaching the photoreceptors, to scavenge hydroxyradicals and to protect retinal pigment epithelium (RPE) cells from oxidative damage. Therefore, it is reasonable to think that the physiological decrease of melatonin in aged people may be an important factor in RPE dysfunction, which is a well known cause for initiation of AMD. Our purpose is to explore a new approach to prevent or treat AMD. We began case control study with a follow-up of 6 to 24 months. One hundred patients with AMD were diagnosed and 3 mg melatonin was given orally each night at bedtime for at least 3 months. Both dry and wet forms of AMD were included. Fifty-five patients were followed for more than 6 months. At 6 months of treatment, the visual acuity had been kept stable in general. Though the follow up time is not long, this result is already better than the otherwise estimated natural course.1,2 The change of the fundus picture was remarkable. Only 8 eyes showed more retinal bleeding and 6 eyes more retinal exudates. The majority had reduced pathologic macular changes. We conclude that the daily use of 3 mg melatonin seems to protect the retina and to delay macular degeneration. No significant side effects were observed.

[Acute retinal necrosis: a report of 19 cases].

PURPOSE: To improve the diagnose and treatment capacity on acute retinal necrosis (ARN). METHODS: Retrospectively analyse the manifestation, examination, diagnose, treatment and prognosis of the 19 cases with ARN in our Ophthalmic Center from January, 1996 to November, 2003. RESULTS: Nineteen cases had inflammation in anterior segment, vitritis, necrotizing retinitis and retinal vasculitis, except one patient. After treatment, visual acuity had been improved in 11 eyes (45.8%). Final visual acuity were lower than 0.05 in 11 eyes. Signs were controlled in 21 eyes(87.5%). CONCLUSIONS: The diagnose of ARN should be mainly based on clinical manifestation. Early and sufficient treatment with antiviral agents, corticosteroid and prophylactic laser photocoagulation, sometimes vitrectomy are the key point to control the disease.