Xuyang Liu

Amorphous phase and morphological structure of hydroxyapatite plasma coatings

It is shown that under standard conditions of plasma spraying hydroxyapatite powder reaches the substrate in the form of molten drops. On striking the surface, the molten drop splatters, cools rapidly and solidifies. Consequently, a pancake particle surrounded by tiny spherical or differently shaped particles is formed on the substrate. The solidified particles are partly crystallized. Besides the crystalline hydroxyapatite, they contain some supercooled molten hydroxyapatite, i.e. amorphous hydroxyapatite. Build-up of these particles during coating gives a porous pancake-globular structure. During a brief vacuum heating at 630 degrees C, the amorphous phase is crystallized and completely crystalline hydroxyapatite coatings are obtained.

Phase and structural changes in hydroxyapatite coatings under heat treatment.

Hydroxyapatite (HA) crystallites of smaller size than those formed during the spraying process are found in HA coatings on titanium as a result of the crystallization of the amorphous phase (approximately 630 degrees C) when the coatings are vacuum-heat-treated in the temperature interval 100-1000 degrees C. As the annealing temperature increases within the 630-1000 degrees C range, the size of the crystallites increases, and at 1000 degrees C reaches the size of those formed during the process of spraying. At the same time, at 800 degrees C and above, HA transforms into other calcium phosphate phases (alpha-tricalcium phosphate, beta-tricalcium phosphate, tetracalcium monoxide diphosphate). These phase transformations lead to the increase of coating roughness.

Exome Sequencing Identifies Compound Heterozygous Mutations in CYP4V2 in a Pedigree with Retinitis Pigmentosa

Retinitis pigmentosa (RP) is a heterogeneous group of progressive retinal degenerations characterized by pigmentation and atrophy in the mid-periphery of the retina. Twenty two subjects from a four-generation Chinese family with RP and thin cornea, congenital cataract and high myopia is reported in this study. All family members underwent complete ophthalmologic examinations. Patients of the family presented with bone spicule-shaped pigment deposits in retina, retinal vascular attenuation, retinal and choroidal dystrophy, as well as punctate opacity of the lens, reduced cornea thickness and high myopia. Peripheral venous blood was obtained from all patients and their family members for genetic analysis. After mutation analysis in a few known RP candidate genes, exome sequencing was used to analyze the exomes of 3 patients III2, III4, III6 and the unaffected mother II2. A total of 34,693 variations shared by 3 patients were subjected to several filtering steps against existing variation databases. Identified variations were verified in the rest family members by PCR and Sanger sequencing. Compound heterozygous c.802-8_810del17insGC and c.1091-2A>G mutations of the CYP4V2 gene, known as genetic defects for Bietti crystalline corneoretinal dystrophy, were identified as causative mutations for RP of this family.

Soluble amyloid β oligomers may contribute to apoptosis of retinal ganglion cells in glaucoma

Glaucoma is one of the leading causes of visual impairment and blindness. It is characterized by excavation of optic nerve head and visual field loss. Even though the pathogenesis of glaucoma remains unclear, it is generally accepted that elevated intraocular pressure is the major risk factor. No matter what the specific initiators are, retinal ganglion cells are believed to die via apoptosis eventually. It is known that glaucoma correlates strongly with Alzheimers disease and the two diseases share many similarities in pathogenic mechanisms. Recent studies have indicated that amyloid beta peptide, which is implicated in the progression of Alzheimers disease, may be also responsible for retinal ganglion cells death in glaucoma. Amyloid beta exists in different forms, including monomers, oligomers and fibrils, and among these, as demonstrated by extensive evidences, soluble amyloid beta oligomers rather than insoluble amyloid beta fibrils induced apoptosis of neurons in Alzheimers disease. Here we propose that soluble amyloid beta oligomers may play an important role in activation of apoptotic cascades in retinal ganglion cells in glaucoma.

Ocular Blood Flow and Normal Tension Glaucoma

Normal tension glaucoma (NTG) is known as a multifactorial optic neuropathy characterized by progressive retinal ganglion cell death and glaucomatous visual field loss, even though the intraocular pressure (IOP) does not exceed the normal range. The pathophysiology of NTG remains largely undetermined. It is hypothesized that the abnormal ocular blood flow is involved in the pathogenesis of this disease. A number of evidences suggested that the vascular factors played a significant role in the development of NTG. In recent years, the new imaging techniques, fluorescein angiography, color Doppler imaging (CDI), magnetic resonance imaging (MRI), and laser speckle flowgraphy (LSFG), have been used to evaluate the ocular blood flow and blood vessels, and the impaired vascular autoregulation was found in patients with NTG. Previous studies showed that NTG was associated with a variety of systemic diseases, including migraine, Alzheimers disease, primary vascular dysregulation, and Flammer syndrome. The vascular factors were involved in these diseases. The mechanisms underlying the abnormal ocular blood flow in NTG are still not clear, but the risk factors for glaucomatous optic neuropathy likely included oxidative stress, vasospasm, and endothelial dysfunction.

Neuroprotective effects of C-type natriuretic peptide on rat retinal ganglion cells.

PURPOSE. To evaluate the potential neuroprotective effects of C-type natriuretic peptide (CNP) on rat retinal ganglion cells (RGCs). METHODS. Cultured adult rat retinal cells were treated with vehicle, CNP, or atrial natriuretic peptide (ANP), followed by cytotoxic insults (glutamate, TNFalpha, or withdrawal of trophic factor). RGC survival was analyzed by counting Thy-1-positive cells in each well. For in vivo evaluation, N-methyl-d-aspartate (NMDA) with or without CNP was injected intravitreally into rat eyes. At various time points after injection, retinal cross-sections were analyzed for thickness changes in the retinal layers, and retinal flat mounts were assessed by counting cresyl violet-labeled or TUNEL-positive cells. Expressions of natriuretic peptide receptor-B (NPRB) and apoptosis-related genes in retina, including Bcl-xL, BAX, and micro-calpain, were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS. At 50 and 500 nM, CNP, but not ANP, significantly (P < 0.05) protected against glutamate-insult and trophic factor withdrawal-induced RGC death in vitro. Neither peptide significantly affected TNFalpha-induced cytotoxicity. Intravitreal injection of NMDA (20 nanomoles) significantly (P < 0.05) decreased the thickness of the inner plexiform layer (IPL), induced cell loss, increased the number of TUNEL-positive cells in the RGC layer, and upregulated the expression of Bcl-xL, BAX, and micro-calpain. All these effects were significantly (P < 0.05) alleviated by concomitant injection of CNP (4.5 nmol, 10 microg). The neuroprotective effects of CNP were maintained up to 14 days after CNP injection. CONCLUSIONS. CNP protects rat RGCs against the apoptotic damage induced by insults such as excitatory amino acid, both in vitro and in vivo.

Is low dose of Estrogen beneficial for prevention of glaucoma

Glaucoma, as characterized by accelerated retinal ganglion cell (RGC) death and cupping of optic nerve head (ONH), is one of the leading causes of blindness worldwide. Elevated intraocular pressure (IOP) is generally considered as a major risk factor in the pathogenesis of glaucoma. Previous studies showed that glaucoma caused decrease in collagen and elastin density in several ocular tissues, such as lamina cribrosa, peripapillary sclera and cornea, and resulted in reduced elasticity and compliance of these tissues. It is known that estrogen has protective effects against glaucoma, yet the underlying mechanism still remains obscure. Prior researches have provided evidences showing that the estrogen receptors (ERs) express in a variety of the ocular tissues. Estrogen activates the synthesis of collagen fiber and improves the compliance of these tissues. This leads to a reasonable postulation that increased estrogen may result in a higher content of the collagen fibers and enhanced flexibility of the whole eye, which would therefore decrease IOP. Particularly, the increase in the amounts of collagen fibers at lamina cribrosa improves its compliance, which in turn relieves its compression on RGC axons. Therefore, even at the same IOP level, the softening of cribriform foramina yields a more flexible environment for the RGCs to survive. We therefore hypothesize that estrogen at proper dosage can be considered as a potential therapy for glaucoma since it is able to prevent the eye from glaucomatous damage and lower IOP, especially for those menopausal women with glaucoma.

Non-Mitogenic Human Acidic Fibroblast Growth Factor Reduces Retinal Degeneration Induced by Sodium Iodate

PURPOSE To investigate the protective effects of non-mitogenic human acidic fibroblast growth factor on retinal degeneration induced by NaIO(3) in rats. METHODS Retinal degeneration was induced in adult male Wistar rats via caudal-vein injection of 1% NaIO(3) at 50 mg/kg. One h after NaIO(3) treatment, the right eyes received intravitreal injection of 2.5 microg nm-haFGF in 10 microL saline and the left eyes received saline alone as vehicle-treated eyes. Retinal function in rats was evaluated by electroretinogram (ERG) before injection and 1, 7, and 21 days postinjection. Additional rat eyes were enucleated 7 and 21 days postinjection, fixed, and processed for histological examination. RESULTS A model of retinal degeneration in rat was established successfully using NaIO(3) injection. Significant decreases in both ERG a- and b-wave amplitudes were detected in NaIO(3)-injected rats when compared with the normal animals (P < 0.05) on day 7 postinjection. Importantly, at the seventh day after intravitreal nm-haFGF treatment on NaIO(3)-injected rats, the nm-haFGF-treated eyes showed a significant improvement in the ERG amplitudes of both a- and b-waves when compared with vehicle-treated eyes (P < 0.05). In addition, the disruptions of photoreceptor outer segments and the retinal pigment epithelium monolayer were much less frequently observed in the nm-haFGF-treated eyes than the vehicle-treated eyes, and the outer nuclear layer thickness in the nm-haFGF-treated eyes was similar to that of the normal eyes. CONCLUSIONS Intravitreal delivery of nm-haFGF appears to have neuroprotective effect on retinal degeneration induced by NaIO(3).

Myopia: A collagen disease?

Myopia is an increasingly important public health problem in the world. Even though previous studies have strongly implicated a role of certain environmental factors such as visual near-work in myopia development, the pathogenesis of this disease still remains unclear. There is evidence showing that myopia is primarily a hereditary condition, combined with or without environmental influence or individual habitual factors. Recent research suggests that collagens in the sclera play an important role in the development of myopia. Based on a literature review after a Medline search on articles on myopia, changes in scleral collagen appeared to underlie or be associated with the pathogenetic factors (including inheritance) involved in myopia development. Therefore, we hypothesized that myopia is a disorder, in which alterations of scleral collagens may be responsible for the pathological changes found in it.

Single nucleotide polymorphism of MYOC affected the severity of primary open angle glaucoma

AIM To detect the mutations in two candidate genes, myocilin (MYOC) and cytochrome P450 1B1 (CYP1B1), in a Chinese family with primary open angle glaucoma (POAG). METHODS The family was composed of three members, the parents and a daughter. All members of the family underwent complete ophthalmologic examinations. Exons of MYOC and CYP1B1 genes were screened for sequence alterations by polymerase chain reaction (PCR) and direct DNA sequencing. RESULTS The mother was the proband, she was diagnosed as POAG in both eyes. Her daughter was diagnosed as juvenile-onset POAG. The father was asymptomatic. One MYOC heterozygous mutation c.1150 G>A (D384N) in exon 3 was identified in the mother, another MYOC heterozygous variation c.1058 C>T (T353I) in exon 3 was identified in the father, and the daughter inherited both of the variations. Meanwhile, three single nucleotide polymorphisms (SNPs) in CYP1B1 gene were found in the family. CONCLUSION The D384N mutation of MYOC has been reported as one of disease-causing mutations in POAG, whereas T353I variation of MYOC was thought as a high risk factor for POAG. The two variations of MYOC were first reported in one juvenile-onset POAG patient who presented with more severe clinical manifestations, suggesting that T353I polymorphism of MYOC may be associated with the severity of POAG.