Safety evaluation and pharmacodynamics of minocycline hydrochloride eye drops.

PURPOSE: This study evaluated the safe dosage of minocycline hydrochloride (Mino) eye drops and investigated the potential for the prevention or reduction of retinal damage in a diabetic rat model. METHODS: Various concentrations of Mino were applied to human corneal epithelial cells (HCECs) to determine the half maximal inhibitory concentration (IC50). The safety of Mino eye drops was evaluated on Sprague-Dawley (SD) rat eyes by slit-lamp examination, electroretinography (ERG), histology, and TUNEL assay. Eye drops (1 mg/ml) were applied to the streptozotocin-induced diabetic SD rats. Clinical observations, ERG analyses, and optical coherence tomography analyses were performed monthly for five months. Eyes were then analyzed via histology, blood-retinal barrier function assay, and retinal vascular staining. RESULTS: Cytotoxicity analysis using HCECs revealed that the IC50 was 250 µg/ml. Safety analyses in healthy SD rats showed that Mino eye drops did not demonstrate any ocular toxicity. Pharmacodynamics analysis showed that retinal thickness at three months was greater in the Mino group than in the non treated (NT) group. The peak times and amplitudes of each program were better in the Mino group than in the NT group at each time point by ERG analyses. Histology examinations showed a thinner ganglion cell layer, fewer ganglion cells, and more dilated blood vessels in the NT group than in the Mino group. CONCLUSION: Mino eye drops at 1 mg/ml were safe when used in SD rats. Mino eye drops can protect the retina from the development or progression of diabetic retinopathy.

Intravitreally Injected Methylene Blue Protects Retina against Acute Ocular Hypertension in Rats.

PURPOSE: To assess the neuroprotective effects of methylene blue (MB) in a rat model of acute ocular hypertension (AOH) and explore its possible mechanisms. METHODS: Our AOH rat model was obtained with anterior chamber perfusion for 60 min. After that, 100 µM MB was injected into the vitreous cavity immediately after injury. Electroretinogram, fundus photography, optical coherence tomography (OCT) and retina morphology examination were utilized to quantify retinal damage before surgery, as well as 7, 14 and 28 days after. The average number of surviving retinal ganglion cells (RGCs) was counted after fluorescent retrograde labelling with 4% DiI. And TUNEL assay was used to investigate retinal cell apoptosis at 24 hours after AOH. Nrf2 and BACE1 in the retina were determined by RT-qPCR analysis. RESULTS: AOH did produce a severe degeneration effect on the whole retinal layer. Intravitreally injected MB maintained certain retinal thickness after AOH, reduced the destruction of electroretinograms, and enhanced RGCs survival. The average number of TUNEL-labelled cells statistically reduced in the MB-treated retina tissue compared with retina treated with normal saline. The relative mRNA level of Nrf2 was also much higher in the MB-treated retinas after AOH, and the expression of BACE1 had a decline in the AOH + MB group. CONCLUSIONS: MB can protect the retina from AOH injury and the possible mechanism might involve the inhibition of BACE1 expression and the activation of Nrf2 antioxidant pathway.

Neuroprotective effect of minocycline on rat retinal ischemia-reperfusion injury.

Purpose: To examine the neuroprotective effect of minocycline on retinal ischemia-reperfusion (IR) injury in rats and investigate its possible mechanism of action. Methods: Retinal IR injury was established by increasing the intraocular pressure in rats up to 110 mmHg for 60 min. The animals with retinal IR injury were intraperitoneally injected with 22.5 mg/kg minocycline twice a day for 14 days. The control group received the same amount of saline. Subsequently, funduscopic examination, retinal thickness measurement, retinal microvascular morphology, full-field electroretinography (ERG), retinal apoptotic cell count, and remaining retinal ganglion cell (RGC) count were performed. The expression of iNOS, Bax, Bcl2, IL-1α, IL-6, TNF-α, caspase-3, GFAP, Iba-1, Hif-1α, and Nrf2 was examined with real-time PCR and western blotting. Results: Minocycline treatment prevented IR-induced rat retinal edema and retinal cells apoptosis at the early stage and alleviated retina atrophy, blood vessel tortuosity, functional photoreceptor damage, and RGC degeneration at the late stage of the IR injury. At the molecular level, minocycline affected retinal gene and protein expression induced by IR. Conclusions: The results suggested that minocycline has a neuroprotective effect on rat retinal IR injury, possibly through anti-inflammation, antiapoptosis, antioxidation, and inhibition of microglial activation.

Synthesis of Fe-Fe3O4/rGO Composite with Heterostructure Through Room-Temperature Reduction as Photo-Fenton Catalyst.

A Fe-Fe3O4/rGO nanocomposite with heterostructure has been successfully synthesized by a highyield, low-cost, and easily operated room-temperature reduction method. The novel Fe-Fe3O4/rGO composite exhibits an excellent activity for the degradation of Orange II under visible light by the Photo-Fenton process, which is 92.06% after 180 minutes. Moreover, magnetic analysis indicated that the prepared Fe-Fe3O4/rGO composite possesses ferromagnetic properties, which enable it to be magnetically separated for recycling purposes.

Highly sensitive and selective electrochemical immunosensors by substrate-enhanced electroless deposition of metal nanoparticles onto three-dimensional graphene@Ni foams.

In this study, we have for the first time preformed the facile substrate-enhanced electroless deposition (SEED) of metal nanoparticles onto monolithic graphene@Ni foams for construction of disposable three-dimensional (3D) electrochemical immunosensors. Specifically, we firstly used the SEED method to deposit gold nanoparticles (AuNPs) onto the graphene@Ni foam for immobilization of antibody (Ab1). This is followed by a second step SEED deposition to produce silver nanoparticles (AgNPs) for electrochemical stripping detection. Using α-fetoprotein antigen (AFP) as a module analyte, the newly-developed sensor showed a wide linear response, ranging from 5.0 pg/mL to 5.0 ng/mL and a low detection limit down to 2.3 pg/mL. The newly-developed 3D-immunosensor is sensitive, reliable, and easy to be fabricated, showing great potential for clinic applications.