Zizhong Hu

Topical delivery of growth hormone releasing peptide using liposomal systems: An in vitro study using hairless mouse skin

The results of this study clearly demonstrates the utility of novel non-ionic liposomal systems in facilitating transfer of GHRP-6 into and across deeper strata of skin following topical application. These findings indicate that it may be possible to deliver therapeutic doses of a wide variety of peptides to local skin tissue via topical application. The results also suggest the possibility of controlled enhancement of skin penetration or metered polypeptide deposition through appropriate choice of liposomal lipid components. The pronounced enhancement of GHRP-6 and mannitol transport from emulsions containing the nonionic lipids suggests a promising delivery system for hydrophilic drugs in general.

Protective effect of alpha-mangostin against oxidative stress induced-retinal cell death

It is known that oxidative stress plays a pivotal role in age-related macular degeneration (AMD) pathogenesis. Alpha-mangostin is the main xanthone purified from mangosteen known as anti-oxidative properties. The aim of the study was to test the protective effect of alpha-mangostin against oxidative stress both in retina of light-damaged mice model and in hydrogen peroxide (H2O2)-stressed RPE cells. We observed that alpha-mangostin significantly inhibited light-induced degeneration of photoreceptors and 200 μM H2O2-induced apoptosis of RPE cells. 200 μM H2O2-induced generation of reactive oxygen species (ROS) and light-induced generation of malondialdehyde (MDA) were suppressed by alpha-mangostin. Alpha-mangostin stimulation resulted in an increase of superoxide dismutase (SOD) activity, glutathione peroxidase (GPX) activity and glutathione (GSH) content both in vivo and vitro. Furthermore, the mechanism of retinal protection against oxidative stress by alpha-mangostin involves accumulation and the nuclear translocation of the NF-E2-related factor (Nrf2) along with up-regulation the expression of heme oxygenas-1 (HO-1). Meanwhile, alpha-mangostin can activate the expression of PKC-δ and down-regulate the expression of mitogen-activated protein kinases (MAPKs), including ERK1/2, JNK, P38. The results suggest that alpha-mangostin could be a new approach to suspend the onset and development of AMD.

Association between variants A69S in ARMS2 gene and response to treatment of exudative AMD: a meta-analysis

A study was undertaken to investigate the association between A69S in age-related maculopathy susceptibility 2 (ARMS2) and the response to anti-angiogenesis treatment in exudative age-related macular degeneration (AMD). A literature-based meta-analysis was performed of studies relevant to A69S and the response to anti-angiogenesis treatment. PubMed, Web of Science, China National Knowledge Infrastructure (CNKI) and Sinomed databases were used to retrieve articles up to July 2014. Pooled ORs and 95% CIs were estimated using fixed and random effects models in Stata V.9.0. Q-statistic testing was used to assess heterogeneity. Twelve articles comprising 2389 cases were included in the final meta-analysis. The analysis of the overall population indicated a statistically significant association between A69S and the response to anti-angiogenesis treatment in exudative AMD (GG vs TT: OR 1.34 (95% CI 1.01 to 1.77), p=0.039; GT vs TT: OR 1.58 (95% CI 1.08 to 2.31), p=0.018; GG+GT vs TT: OR 1.74 (95% CI 1.19 to 2.52), p=0.004). In subgroup analysis, A69S appeared more likely to be a predictor for anti-angiogenic response in the East Asian population (GG vs TT: OR 1.65 (95% CI 1.02 to 2.68), p=0.042; GT vs TT: OR 1.66 (95% CI 1.17 to 2.37), p=0.005; GG+GT vs TT: OR 1.82 (95% CI 1.07 to 3.10), p=0.027; G vs T: OR 1.56 (95% CI 1.01 to 2.41)). However, no statistical significance was found in the Caucasian subgroup analysis. This study shows an association between A69S polymorphism in the ARMS2 gene and the anti-angiogenesis treatment response. A69S could be considered predictive of the anti-angiogenic effects, especially in Asian populations.

Face-down or no face-down posturing following macular hole surgery: a meta-analysis.

To evaluate the impact of postoperative posturing with or without face‐down on the anatomical and functional outcomes of macular hole surgery.

Tyrosine-mutated AAV2-mediated shRNA silencing of PTEN promotes axon regeneration of adult optic nerve

Activating PI3K/AKT/mTOR signaling pathway via deleting phosphatase and tensin homolog (PTEN) has been confirmed to enhance intrinsic growth capacity of neurons to facilitate the axons regeneration of central nervous system after injury. Considering conditional gene deletion is currently not available in clinical practice, we exploited capsid residue tyrosine 444 to phenylalanine mutated single-stranded adeno-associated virus serotype 2 (AAV2) as a vector delivering short hairpin RNA to silence PTEN to promote retinal ganglion cells (RGCs) survival and axons regeneration in adult rat optic nerve axotomy paradigm. We found that mutant AAV2 displayed higher infection efficiency to RGCs and Müller cells by intravitreal injection, mediated PTEN suppression, resulted in much more RGCs survival and more robust axons regeneration compared with wild type AAV2, due to the different extent of the mTOR complex-1 activation and glutamate aspartate transporter (GLAST) regulation. These results suggest that high efficiency AAV2-mediated PTEN knockdown represents a practicable therapeutic strategy for optic neuropathy.

Application of 3-dimensional printing technology to construct an eye model for fundus viewing study.

Objective To construct a life-sized eye model using the three-dimensional (3D) printing technology for fundus viewing study of the viewing system. Methods We devised our schematic model eye based on Navarros eye and redesigned some parameters because of the change of the corneal material and the implantation of intraocular lenses (IOLs). Optical performance of our schematic model eye was compared with Navarros schematic eye and other two reported physical model eyes using the ZEMAX optical design software. With computer aided design (CAD) software, we designed the 3D digital model of the main structure of the physical model eye, which was used for three-dimensional (3D) printing. Together with the main printed structure, polymethyl methacrylate(PMMA) aspherical cornea, variable iris, and IOLs were assembled to a physical eye model. Angle scale bars were glued from posterior to periphery of the retina. Then we fabricated other three physical models with different states of ammetropia. Optical parameters of these physical eye models were measured to verify the 3D printing accuracy. Results In on-axis calculations, our schematic model eye possessed similar size of spot diagram compared with Navarros and Bakarajus model eye, much smaller than Arianpours model eye. Moreover, the spherical aberration of our schematic eye was much less than other three model eyes. While in off- axis simulation, it possessed a bit higher coma and similar astigmatism, field curvature and distortion. The MTF curves showed that all the model eyes diminished in resolution with increasing field of view, and the diminished tendency of resolution of our physical eye model was similar to the Navarros eye. The measured parameters of our eye models with different status of ametropia were in line with the theoretical value. Conclusions The schematic eye model we designed can well simulate the optical performance of the human eye, and the fabricated physical one can be used as a tool in fundus range viewing research.

Association between transcription factor 7-like 2 rs7903146 polymorphism and diabetic retinopathy in type 2 diabetes mellitus: A meta-analysis

As one of the vascular complications of type 2 diabetes mellitus, the incidence of diabetes retinopathy is greatly increasing worldwide. Both genetic and environmental factors are involved in the pathologies. A meta-analysis was conducted to assess the association between transcription factor 7-like 2 polymorphism (rs7903146) and type 2 diabetic retinopathy. Published literature from PubMed, Web of Science and China National Knowledge Infrastructure were retrieved. Pooled odds ratios with 95% confidence intervals were calculated to estimate the strength of the association. Eight studies including 6422 participants were included in the final meta-analysis. Our analysis provides substantial evidence that the rs7903146 variant is significantly associated with the risk of diabetic retinopathy in Caucasian populations while not in East Asian populations. The variant of rs7903146 appeared more likely to be a promising genetic biomarker of diabetic retinopathy in Caucasians.

Photoacoustic imaging features of intraocular tumors: Retinoblastoma and uveal melanoma

The purpose of this study is to examine the capability of photoacoustic (PA) imaging (PAI) in assessing the unique molecular and architectural features in ocular tumors. A real-time PA and ultrasonography (US) parallel imaging system based on a research US platform was developed to examine retinoblastoma in mice in vivo and human retinoblastoma and uveal melanoma ex vivo. PA signals were generated by optical illumination at 720, 750, 800, 850, 900 and 950 nm delivered through a fiber optical bundle. The optical absorption spectra of the tumors were derived from the PA images. The optical absorption spectrum of each tumor was quantified by fitting to a polynomial model. The microscopic architectures of the tumors were quantified by frequency domain analysis of the PA signals. Both the optical spectral and architectural features agree with the histological findings of the tumors. The mouse and human retinoblastoma showed comparable total optical absorption spectra at a correlation of 0.95 (p<0.005). The quantitative PAI features of human retinoblastoma and uveal melanoma have shown statistically significant difference in two tailed t-tests (p<0.05). Fully compatible with the concurrent procedures, PAI could be a potential tool complementary to other diagnostic modalities for characterizing intraocular tumors.

Knockout of Ccr2 alleviates photoreceptor cell death in rodent retina exposed to chronic blue light

Age-related macular degeneration (AMD), the leading cause of visual loss after the age of 60 years, is a degenerative retinal disease involving a variety of environmental and hereditary factors. Although it has been implicated that immune system is involved in the disease progression, the exact role that microglia has is still unclear. Here we demonstrated that knockout of Ccr2 gene could alleviate photoreceptor cell death in mice retinas exposed to chronic blue light. In Ccr2−/− mice, a damaged microglia recruitment was shown in retina and this could protect the visual function in electroretinogram and alleviate the photoreceptor apoptosis, which thus helped attenuate the blue light-induced retinopathy. We further found an increased co-location of NLRP3, Iba-1, and IL-1β in fluorescence and a concomitant increased protein expression of NLRP3, caspase-1, and IL-1β in western blotting in chronic blue light-induced retinopathy. Moreover, the activation of microglia and their cellular NLRP3 inflammasomes occurred as an earlier step before the structural and functional damage of the mice retinas, which collectively supported that microglial NLRP3 inflammasome might be the key to the chronic blue light-induced retinopathy.

High-precision, non-invasive anti-microvascular approach via concurrent ultrasound and laser irradiation

Antivascular therapy represents a proven strategy to treat angiogenesis. By applying synchronized ultrasound bursts and nanosecond laser irradiation, we developed a novel, selective, non-invasive, localized antivascular method, termed photo-mediated ultrasound therapy (PUT). PUT takes advantage of the high native optical contrast among biological tissues and can treat microvessels without causing collateral damage to the surrounding tissue. In a chicken yolk sac membrane model, under the same ultrasound parameters (1 MHz at 0.45 MPa and 10 Hz with 10% duty cycle), PUT with 4 mJ/cm2 and 6 mJ/cm2 laser fluence induced 51% (p = 0.001) and 37% (p = 0.018) vessel diameter reductions respectively. With 8 mJ/cm2 laser fluence, PUT would yield vessel disruption (90%, p < 0.01). Selectivity of PUT was demonstrated by utilizing laser wavelengths at 578 nm or 650 nm, where PUT selectively shrank veins or occluded arteries. In a rabbit ear model, PUT induced a 68.5% reduction in blood perfusion after 7 days (p < 0.001) without damaging the surrounding cells. In vitro experiments in human blood suggested that cavitation may play a role in PUT. In conclusion, PUT holds significant promise as a novel non-invasive antivascular method with the capability to precisely target blood vessels.