Silica nanoparticle design for colorectal cancer treatment: Recent progress and clinical potential.

Colorectal cancer (CRC) is the third most common cancer worldwide and the second most common cause of cancer death. Nanotherapies are able to selectively target the delivery of cancer therapeutics, thus improving overall antitumor efficiency and reducing conventional chemotherapy side effects. Mesoporous silica nanoparticles (MSNs) have attracted the attention of many researchers due to their remarkable advantages and biosafety. We offer insights into the recent advances of MSNs in CRC treatment and their potential clinical application value.

Mitochondrial 13513G>A Mutation With Low Mutant Load Presenting as Isolated Leber's Hereditary Optic Neuropathy Assessed by Next Generation Sequencing.

Objective: Mitochondrial 13513G>A mutation presenting as isolated Leber's hereditary optic neuropathy (LHON) without any extraocular pathology has not been reported in literature. We herein evaluate the clinical characteristics and heteroplasmy of m.13513G>A mutation manifesting as isolated LHON. Methods: Seven members of a Chinese family were enrolled in this study. All subjects underwent detailed systemic and ophthalmic examinations. Mitochondrial DNA in their blood was assessed by targeted PCR amplifications, next generation sequencing (NGS), and pyrosequencing. One hundred of blood samples from ethnic-matched healthy volunteers were tested by NGS and pyrosequencing as normal controls. Results: Isolated LHON without any other ocular or extraocular pathology was identified in a 16 year old patient in this family. Heteroplasmic m.13513G>A mutation was detected by NGS of the full mtDNA genome in the patient with mutant load of 33.56%, and of 26% 3 months and 3 years after the onset of LHON, respectively. No m.13513G>A mutation was detected in all his relatives by NGS. Pyrosequencing revealed the mutant load of m.13513G>A mutation of the LHON patient, his mother, father and sister were 22.4, 1.9, 0, and 0%, respectively. None of 100 healthy control subjects was detected to harbor m.13513G>A mutation either by NGS or by pyrosequencing of the full mt DNA genome. Conclusions: We first report m.13513G>A mutation with low mutant load presenting as isolated LHON. NGS of the full mitochondrial DNA genome is highly recommended for LHON suspects when targeted PCR amplification for main primary point mutations of LHON was negative.

Quality of life in adult intermittent exotropia and the risk factors.

AIM: To study the quality of life of adult patients with intermittent exotropia (IXT) in China and analyze the factors affecting the quality of life in IXT patients. METHODS: Totally 109 cases of normal eye (control group), 77 cases of IXT (IXT group) and 115 cases of strabismus control group (except IXT) were collected. The quality of life of the patients was assessed by Chinese version of adult strabismus patient's quality of life scale (CAS-20). The differences of general characteristics, visual function and quality of life were analyzed, and the effects of individual factors and visual function on quality of life of patients with IXT were analyzed. RESULTS: The IXT group had a high proportion of patients with family history, low proportion of patients with amblyopia compared with strabismus control group. The proportion with normal near and far stereopsis of IXT group were lower than that of normal control group. The best corrected visual acuity of IXT group was higher than that of strabismus control group, but lower than the control group. In addition, the median strabismus degree in IXT group was higher than that in other strabismus control group. The median psychosocial scores and median visual function scores of the IXT group was lower than that of the normal control group, but not different from strabismus control group. Occupation status, course of disease, far stereopsis and near stereopsis significantly affected the quality of life in IXT patients. CONCLUSION: Adult IXT patients in China have a certain proportion of family history and lower quality of life, The main factors affecting the quality of life of IXT patients is stereopsis, course of disease and occupation status.

OPA1 haploinsufficiency due to a novel splicing variant resulting in mitochondrial dysfunction without mitochondrial DNA depletion.

Background: To identify and investigate the effects of a novel splicing variant, c.1444-2A>C of OPA1, on its transcript, translation, and mitochondrial function, which was found in an 8-year-old patient with dominantly inherited optic atrophy (DOA). Materials and Methods: The clinical evaluations were performed at the Eye Center. Lymphoblast cell lines were generated from the patient, mother, and a normal control with the same haplotype of mitochondrial genome. The novel variant was confirmed by Sanger sequencing. The splicing alteration of cDNA was checked by both Sanger sequencing and agarose gel. OPA1 expression was carried out by RT-PCR and Western blotting. Transmission electron microscopy was used for mitochondrial morphology. Mitochondrial functions, including the rates of oxygen consumption, ATP generation, ROS product and membrane potential were assayed in lymphoblast cells. Results: The novel OPA1 splicing variant, c.1444-2A>C, led to a deletion of the 15th exon in mRNA transcript. Approximately 50% reduction of mRNA and protein expression was present in mutant cells as compared with controls. No marked depletion of mtDNA nor mitochondrial mass was caused by the splicing variant. However, defects that the impaired capacity of OXPHOS, reduced ATP generation, increased ROS and decreased membrane potential were observed in the mutant cells, which promoted a ubiquitin-binding mitophagy instead of apoptosis. Conclusions: The novel splicing variant, c.1444-2A>C resulted in OPA1 haploinsufficiency effect on its expression and mitochondrial function without mtDNA depletion. Our findings may provide new insights into the understanding of pathophysiology of DOA.

Dimensions of the ciliary muscles of Brücke, Müller and Iwanoff and their associations with axial length and glaucoma.

BACKGROUND: To assess the dimensions of Brücke's muscle, as the longitudinal portion, and of Müller's muscle and Iwanoff's muscle combined as circular and radial/reticular portions of the ciliary muscle. METHODS: The histomorphometric study included human globes that had been enucleated due to an ocular tumor or end-stage glaucoma. After immunohistochemical staining of the ciliary muscles, the histology slides were examined under a light microscope applying a digitized image analysis system. RESULTS: The study included 55 globes [axial length 25.6 ± 3.0 mm (range 21.0 mm-36.0 mm)] from 55 patients [mean age, 33.7 ± 18.3 years (range:1-66 years)]. Length of Brücke's muscle (mean 3.40 ± 0.76 mm) increased with longer axial length (P < 0.001; regression coefficient beta: 0.52) and was not significantly associated with age (P = 0.12), presence of glaucoma (P = 0.11) or Brücke's muscle thickness at the scleral spur (P = 0.32), at the site of the maximum thickness of the ciliary body (P = 0.84) or at the posterior end of Müller's/Iwanoff's muscle (P = 0.66), or with thickness (P = 0.29) and cross-sectional area (P = 0.85) of Müller's/Iwanoff's muscle. Mean distance between Brücke's muscle end and the ora serrata measured 1.73 ± 1.13 mm and increased with longer axial length (P < 0.001; beta: 0.46). Distance from the scleral spur to the ora serrata (mean: 4.94 ± 1.42 mm; range: 3.08-9.09 mm) increased with longer axial length (P < 0.001; beta: 0.61). Maximal thickness (mean: 245 ± 125 µm) and cross-section area (mean: 0.19 ± 0.11 mm2) of Müller's/Iwanoff's muscle decreased significantly with the diagnosis of glaucoma (P = 0.02;beta:-0.38) and longer axial length (P = 0.03; beta: -0.35). CONCLUSIONS: Length of Brücke's muscle increased with axial length of the globe, while its cross-sectional area was independent of axial length. Müller's/Iwanoff's muscle decreased in cross-sectional area with longer axis, and in particular with the presence of glaucoma, while the dimensions of Brücke's muscle were not related to glaucoma.

Bruch´s membrane thickness in relationship to axial length.

PURPOSE: To assess a potential role of Bruch´s membrane (BM) in the biomechanics of the eye, we measured its thickness and the density of retinal pigment epithelium (RPE) cells in various ocular regions in eyes of varying axial length. METHODS: Human globes, enucleated because of an ocular tumor or end-stage glaucoma were prepared for histological examination. Using light microscopy, the histological slides were histomorphometrically examined applying a digitized image analysis system. RESULTS: The study included 104 eyes with a mean axial length of 27.9±3.2 mm (range:22.6mm-36.5mm). In eyes without congenital glaucoma, BM was significantly thickest (P<0.001) at the ora serrata, followed by the posterior pole, the midpoint between equator and posterior pole (MBEPP), and finally the equator. BM thickness was not significantly correlated with axial length (ora serrata: P = 0.93; equator:P = 0.31; MBEPP:P = 0.15; posterior pole:P = 0.35). RPE cell density in the pre-equatorial region (P = 0.02; regression coefficient r = -0.24) and in the retro-equatorial region (P = 0.03; r = -0.22) decreased with longer axial length, while RPE cell density at the ora serrata (P = 0.35), the MBEPP (P = 0.06; r = -0.19) and the posterior pole (P = 0.38) was not significantly correlated with axial length. Highly myopic eyes with congenital glaucoma showed a tendency towards lower BM thickness and lower RPE cell density at all locations. CONCLUSIONS: BM thickness, in contrast to scleral and choroidal thickness, was independent of axial length in eyes without congenital glaucoma. In association with an axial elongation associated decrease in the RPE cell density in the midperiphery, the findings support the notion of a biomechanical role BM may play in the process of emmetropization/myopization.

Clinical and histopathological features of adenomas of the ciliary pigment epithelium.

PURPOSE: Adenomas of the ciliary pigment epithelium (CPE) are rare benign tumours which have mainly to be differentiated from malignant ciliary body melanomas. Here we report on a consecutive series of patients with CPE adenomas and describe their characteristics. METHODS: The retrospective hospital-based case series study included all patients who were consecutively operated for CPE adenomas. RESULTS: Of the 110 patients treated for ciliary body tumours, five patients (4.5%) had a CPE adenoma. Mean age was 59.0 ± 9.9 years (range: 46-72 years). Mean tumour apical thickness was 6.6 ± 1.7 mm. Tumour colour was mostly homogenously brown to black, and the tumour surface was smooth. The tumour masses pushed the iris tissue forward without infiltrating iris or anterior chamber angle. Sonography revealed an irregular echogram with sharp lesion borders and signs of blood flow in Color Doppler flow imaging. Ultrasonographic biomicroscopy demonstrated medium-low internal reflectivity and acoustic attenuation. In magnetic resonance imaging (MRI), the tumours as compared to brain were hyperintense on T1-weighted images and hypointense on T2-weighted images. Tumour tissue consisted of cords and nests of pigment epithelium cells separated by septa of vascularized fibrous connective tissue, leading to a pseudo-glandular appearance. The melanin granules in the cytoplasm were large and mostly spherical in shape. In four patients, the tumours were hyperpigmented. Tumour cells were large with round or oval nuclei and clearly detectable nucleoli. CONCLUSIONS: These clinical characteristics of CPE adenomas, such as homogenous dark brown colour, smooth surface, iris dislocation and anterior chamber angle narrowing but no iris infiltration, segmental cataract, pigment dispersion, and, as compared to brain tissue, hypointensity and, as compared to extraocular muscles or lacrimal gland, hyperintensity on T2-weighted MRI images, may be helpful for the differentiation from ciliary body malignant melanomas.