硅基纳米探针用于眼部疾病的成像检测与治疗

快速精准的诊断和高效的治疗对于减轻眼部疾病造成的危害至关重要. 在过去的几十年里, 由于具有尺寸小、 比表面积大、 表面易修饰及独特的光/电子/机械性能等优点, 纳米材料已被用于构建不同种类的高性能纳米探针. 其中, 基于其良好的生物相容性, 科学家们已经将硅纳米材料设计为可用于不同眼部疾病诊断与治疗的功能化纳米探针. 本综述主要概述了将硅基纳米探针用于检测和治疗不同眼部疾病(如角膜疾病、 视网膜疾病、 青光眼等)的近期研究进展. 首先, 重点介绍了硅基纳米探针的设计制备及在角膜新生血管、 细菌性角膜炎等角膜疾病的成像检测与治疗中的应用; 然后, 介绍了用于成像检测和治疗视网膜疾病(如色素性视网膜炎和视网膜新生血管)的硅基持续性给药系统的研究成果; 随后, 概述了多功能硅基纳米载药系统的构建及在青光眼治疗领域的应用研究进展; 最后, 简要讨论了将硅基纳米探针用于眼部疾病诊治面临的挑战并对未来的发展前景进行了展望.     

Fungal keratitis infected eye treatment with antibiotic-loaded zinc ions tagged polyvinyl acetate phthalate-g-polypyrrole drug carrier

Currently, the treatment of fungal keratitis (FK) infection remains a major clinical challenge, and current investigations, development in the field have widened approaches. The present work was aimed to synthesis a dual role novel carrier system consisting of Ofloxacin (OFL) and Nepafenac (NF) hydrophobic drugs incorporated in Zinc ions (Zn²⁺) tagged Polyvinyl acetate phthalate (PVAP) grafted Polypyrrole (PPy) carrier (OFL&NF-Zn²⁺/PVAP-g-PPy) to treat FK infection. The FT-IR, SEM, and dynamic light scattering revealed the carrier chemical structure, spherical shape, and the average particle size of 691.3 ± 1 nm. The carrier’s entrapment of OFL and NF drugs has been observed at 78.23% and 60.03%. The carrier exhibited significant antifungal activity at the concentration of 58 mg mL⁻¹ against Candida albicans which was lower than that of the free ofloxacin. The cell viability results suggested up to 70 μg/mL concentration of OFL&NF-Zn²⁺/PVAP-g-PPy did not induce any cytotoxicity on cultured ADSC cells at 48 h treatment time. It confirms the fact that the OFL&NF-Zn²⁺/PVAP-g-PPy carrier showed good biocompatibility and good anti-fungal activity. Thus the carriers provide a significant potential to improve the bioavailability of topically applied drugs to treat fungal eye infection.     

微量元素与眼底病

目前已知有十多种微量微元素与眼的正常生理功能有密切关系。且对多种眼病的发生有很大影响，本文综合介绍微量元素锌、铜、硒与视觉功能的密切关系，以及近年来在脉络膜，视网膜、视神经的几种疾病中有关锌、铜、硒的测定研究进展。     

Vibrational Spectral Biodiagnosis of Ocular Calcification

Abstract

Ocular calcification is a biological mineralization. It is also a well-known human ophthalmic disease but is a complex process because the pathophysiology of calcium deposition in ocular tissues depends on site-specific factors. Calcified deposits in the eyes are asymptomatic lesions; a serious consequence of ocular plaques is the potential partial or total loss of vision in the affected eye. Therefore, a better understanding of the exact compositional components and origin of calcified plaques in different eye tissues is necessary and merits exploration. The present review article includes information on different diagnostic or analytical techniques to examine human ocular calcification collected and compiled from 2005 to 2013, together with data on the application of vibrational spectroscopy in ophthalmology studies from 1990 onwards. This overview of ocular calcification is mainly focused on two aspects: the pathogenesis and mechanism of calcification in different ocular tissues and biomedical applications of vibrational spectroscopy to spectral biodiagnosis of eye tissues. A summary of the in vitro, in situ, and in vivo spectral information that is expected to assist physicians in the diagnosis and treatment of patients or satisfy patients of the clinical competence of the diagnosis is provided.     

The comparison of the proton dose distribution calculated with the treatment planning system and measured with alanine detectors in the eye phantom irradiated under therapeutic conditions

The paper describes the applicability of commercially available alanine detectors produced by Synergy Health for verification of the dose distribution calculated by the treatment planning system (TPS) used in proton eye radiotherapy – Eclipse Ocular Proton Planning (EOPP) program, version 8.9.06, Varian Medical Systems. The TPS-planned dose distribution at selected points in the eye phantom is compared to the dose registered by alanine detectors at these points during a simulated therapeutic irradiation at the proton eye radiotherapy facility in the Henryk Niewodniczanski Institute of Nuclear Physics (IFJ PAN), Krakow, Poland. The phantom was irradiated to obtain, a typical for choroidal melanoma, fraction dose of 15 CGE (13,64 Gy) at the tumor location. The dose registered with alanine pellets located inside the simulated tumor volume demonstrates a good agreement with the TPS-planned dose. The typical for proton radiotherapy, steep dose fall-off outside the treated area is registered by the alanine pellets however, it is difficult to assess it quantitatively, because the dose related EPR signal is registered from the entire pellet volume.     

Analysis of pupil and corneal wave aberration data supplied by the SN CT 1000 topography system

Ocular aberrations depend on pupil size and centring and the retinal image quality under natural conditions differs from that corresponding to laboratory ones. In the present article, pupil and wave aberration data supplied by the Shin Nippon CT 1000 (SN CT 1000) topography system are analysed. Two groups of eyes under natural viewing conditions are considered ((260±20) lux at the eye under study). The first group consists of 10 normal eyes (−1.25 to 3 D sphere; 0 to −1.75 D cylinder) of five young subjects (age between 18 and 33 years). For this group, five determinations per eye are performed and the repeatability of results is analysed. Pupil centre is displaced from corneal vertex towards the temporal region, the largest displacement being (0.5±0.1) mm. The variation of pupil diameter in each eye is less than 21% while the inter-subject variability is large since diameters are between (3±0.3) and (5.3±0.6) mm. Aberrations are evaluated for two different pupil sizes, the natural one and a fictitious one of 6 mm. The corneal higher-order root-mean square wavefront error (RMS_HO) for a 6 mm pupil centred in the corneal vertex, averaged across all eyes, is (0.37±0.06) μm while, considering the natural pupil diameter, the average in each eye is significantly lower, up to eight times smaller. The fourth-order spherical aberration is an important aberration in the considered eyes, its maximum value for a 6 mm pupil being (0.38±0.02) μm. The second group consists of 24 eyes of 12 subjects (age between 25 and 68 years) such that four eyes are of normal adults (1.25 to +6 D sphere; 0 to −0.5 D cylinder), eight have astigmatisms (−5.5 to +3.25 D sphere; −1.5 to −4.5 D cylinder), six have post-refractive surgery (+0.5 to +3.5 D sphere; −0.5 to −4 D cylinder) and six have keratoconus (−9.5 to +1 D sphere; −1 to −4.5 D cylinder). For this group only one determination per eye is performed. Pupil centre is displaced from corneal vertex towards the temporal region except in cases of keratoconus, where there can be a dominant upwards displacement. Pupil diameters are between 2.7 and 5.6 mm. The corneal higher order root mean square wavefront error for a 6 mm pupil ranges between 0.3 (normal eye) and 5.3 μm (keratoconus).     

Evaluation of topographical variation in ocular surface temperature by functional infrared thermography

The objective of this work is to evaluate topographical variation in the ocular surface temperature (OST) among the young, elderly and the subjects wearing contact lens using thermographic methodology. We recorded thermographic sequence lasting of 25 s for each eye. The ocular region in each of the thermal images in the sequence was identified and warped into a standard form. Then, the warped sequence was divided into a number of sub-sequences. A differential image which is an image matrix was obtained from each of these sub-sequences, by subtracting thermal images within the sub-sequence. And the histogram of the differential image was modelled by Gaussian mixture model to discriminate eyelashes from the ocular surface for every thermal image in the sub-sequence. Later, thermal data of eyelashes were eliminated in every thermal image and statistical analysis was performed on the sequences. Finally, topographical profile of each subject group was approximated by equations and illustrated using various temperature profiles. The ocular surface of the young subject was observed to be the warmest, and tear film was determined to play a major role in the topographical and temporal variations in OST. Significant topographical variation was observed among subject groups. Based on our compiled average OST profile (AOSTP), the maximum predictability of the bioheat simulation on ocular model can reach up to 90%.     

Bioinspired self-assembly supramolecular hydrogel for ocular drug delivery

Based on a recent report concerning endogenous agents (i.e., pyridoxal phosphate, adenosine triphosphate, adenosine monophosphate, folinic acid) that modulate the oligomerization of apoptosis-associated speck-like protein (ASC) via the peptide epitope of KKFKLKL, we rationally designed and synthesized a nonapeptide (NapFFKKFKLKL), which can co-assemble with dexamethasone sodium phosphate (Dexp) to generate a NapFFKKFKLKL/Dexp supramolecular hydrogel for ocular drug delivery. The NapFFKKFKLKL/Dexp hydrogel formed instantly after the complexation of NapFFKKFKLKL with Dexp in aqueous solution. The formed supramolecular hydrogels were thoroughly characterized by transmission electron microscopy (TEM), fluorescent spectrum, circular dichroism (CD) spectra and rheology. The peptide concentration significantly affected the in vitro release behavior of Dexp from the supramolecular hydrogel, and the higher peptide concentration resulted in the slower drug release. Following a single intravitreal injection, the proposed NapFFKKFKLKL/Dexp hydrogel displayed good intraocular biocompatibility without having an adverse impact on the retinal architecture and eyesight functions during one month of follow-up. Using an experimental autoimmune uveitis (EAU) rat model, we demonstrated that the resulting NapFFKKFKLKL/Dexp hydrogel had potent capacity to alleviate the intraocular inflammation and retain the morphology of retinal architecture. Overall, the resulting NapFFKKFKLKL/Dexp hydrogel may be a promising drug carrier system to treat various posterior disorders (i.e., uveitis).     

Noninvasive estimation of the ocular elastic modulus for age-related macular degeneration in the human eye using sequential ultrasound imaging

Introduction

Elastic modulus estimation may be an important clinical criterion, as it seems to affect such eye parameters as intraocular pressure, ocular pulsation, blood flow, effect of topical medications, and post-refractive surgery complications. The purpose of this study was to examine the differences in elasticity in the ocular axial length, posterior wall thickness (posterior pole), and retina-choroid thickness under normal and aged-related macular degeneration (AMD) conditions in the human eye by directly estimating the elastic modulus with sequential and noninvasive ultrasound image processing.

Materials and Methods

In this study, 25 healthy subjects and 20 patients with non-neovascular AMD participated in the experiment. The deformation of the ocular axial length, posterior wall thickness and retina-choroid complex thickness was captured using high-resolution ultrasonography before and after loading. The B-mode (20 MHz) and A-mode (8 MHz) frames were obtained and processed with an echo tracking technique. The elastic modulus was estimated using changes in ocular axial length, posterior wall thickness and retina-choroid complex thickness and with applied stress measurements.

Results

There was a significant difference (p < 0.05) in the ocular axial length elastic modulus between the AMD and healthy subjects (AMD patients: 95.165 ± 26.431 kPa, vs. healthy subjects: 49.539 ± 25.867 kPa). Moreover, there was a statistically significant difference (p < 0.05) in the posterior wall thickness elastic modulus between AMD patients and healthy subjects (AMD patients: 50.519 ± 12.295 kPa, vs. healthy subjects: 20.519 ± 11.827 kPa). However, no statistically significant difference (p-value > 0.05) was found in the retina-choroid complex elastic modulus between the two groups (AMD patients: 20.134 ± 3.898 kPa, vs. healthy subjects: 15.630 ± 4.250 kPa).

Conclusion

Although the results were obtained examining a relatively low number of patients, it would appear that noninvasive ultrasound estimation of the local elastic moduli of ocular axial length and posterior wall thickness is suited to aid in detection of the non-exudative AMD thus manifesting its potential as a screening tool in symptom-free individuals.     

Serum and aqueous humour cytokine response and histopathological alterations during ocular Toxoplasma gondii infection in C57BL/6 mice

Toxoplasma gondii, an obligate intracellular protozoan parasite, infects most species of warm-blooded animals, and in humans it causes toxoplasmosis. Healthy people that become infected rarely present clinical symptoms because the immune system prevents the parasite from causing illness. Congenital toxoplasmosis may result in abortion, hydrocephalus, as well as neurological and ocular disease (most frequently retinochoroiditis) of the newborn. In immunocompromised patients, reactivation of latent disease can cause encephalitis. Cell-mediated immunity to T. gondii antigens involves innate acute inflammatory responses and antigen-specific adaptive immunity. Considering the complexity of the immunological events triggered during toxoplasmosis, systemic and local responses were evaluated by cytokine measurements. Aqueous humour and serum were obtained from non-infected and T. gondii Me-49 strain infected C57BL/6 mice for cytokine quantification. Histopathological analyses were made with eyes enucleated from mice after 30 days of infection. ELISA assays showed an increase of IFN-γ levels both in serum and aqueous humour of infected mice in opposition to a decrease in IL-10 levels. On the other hand, TGF-β was high, whereas IL-12 and TNF-α were present in small levels in both groups. We also detected higher levels of IL-4 and IL-6 in aqueous humour than in serum of infected mice when compared to the control group. MIP-2 presented no significant differences between the two groups. Fas and Fas-L were also present in similar levels in serum of non-infected and infected mice, but both chemokines were increased in the aqueous humour of infected mice. Histopathological analysis of infected mice showed inflammatory infiltrates around blood vessels and alteration of the outer photoreceptor segments, on the external and inner nuclear layer. Parasites were observed in 82% of eyes, inside the blood vessels associated with inflammatory infiltrate. Edema, characterized by the increase of interstitial spaces between the FTR, forming lacunae was also noted. These alterations take the form of projections (retino-vitreal), characteristic of retinochoroiditis. In conclusion, T. gondii infection of C57BL/6 mice revealed that cytokine patterns alone do not assure susceptibility or resistance against infection, thus reinforcing the notion that it is necessary more than cytokine dosage to determine Th1 or Th2 profile in this model.