Role of mitochondria in the pathogenesis and treatment of glaucoma / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To gain insight into the potential mechanism of mitochondria dysfunction in pathogenesis, progression and therapeutic management of glaucoma.</p><p><b>DATA SOURCES</b>The data used in this review were mainly published in English from 2000 to present obtained from PubMed. The search terms were "mitochondria", "glaucoma" and "trabecular meshwork" or "retinal ganglion cells".</p><p><b>STUDY SELECTION</b>Articles studying the mitochondria-related pathologic mechanism and treatment of glaucoma were selected and reviewed.</p><p><b>RESULTS</b>Mitochondrial dysfunction or injury was demonstrated in different eye tissue of glaucoma. A variety of potential injuries (light, toxic materials, oxidative injury, mechanical stress, aging, etc.) and the inherent DNA defects are deemed to cause mitochondrial structural and functional destruction in trabecular meshwork cells, retinal ganglion cells, etc. of glaucoma. In addition, various new experimental and therapeutic interventions were used to preserve mitochondrial function, which may be useful for protecting against optic nerve degeneration or reducing the death of retinal ganglion cells in glaucoma.</p><p><b>CONCLUSIONS</b>Mitochondria play an important role in the pathogenesis of glaucoma, various strategies targeting mitochondrial protection might provide a promising way to delay the onset of glaucoma or protect RGCs against glaucomatous damage.</p>

Comparison of combined phacotrabeculectomy with trabeculectomy only in the treatment of primary angle-closure glaucoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Trabeculectomy has become a mainstream treatment in intraocular pressure (IOP) reduction for primary angle-closure glaucoma (PACG); combined trabeculectomy and cataract surgery was reported to reduce IOP and simultaneously improve vision for patients with PACG and coexisting cataract. This study was specialized to compare the efficacy and safety of combined phacotrabeculectomy with that of trabeculectomy only in the treatment of PACG with coexisting cataract.</p><p><b>METHODS</b>This is a comparative case series study. Thirty-one patients (31 eyes) with PACG and coexisting cataract were enrolled. Of these, 17 underwent phacotrabeculectomy and 14 underwent trabeculectomy alone. IOP, filtering blebs, and complications were compared at the final follow-up. Complete success was defined as a final IOP less than 21 mmHg without IOP-lowering medication.</p><p><b>RESULTS</b>After 10 months of postoperative follow-up, the phacotrabeculectomy and trabeculectomy groups showed no significant differences regarding IOP reduction ((20.59 ± 7.94) vs. (24.85 ± 14.39) mmHg, P = 0.614), complete success rate (88% vs. 71%, P = 0.370), formation rate of functioning blebs (65% (11/17) vs. 93% (13/14), P = 0.094), and complications (41% (7/17) vs. 57% (8/14), P = 0.380). IOP-lowering medication was not required for most of the patients in both groups. Additional surgery interventions, including anterior chamber reformation and phacoemulsification, were needed in the trabeculectomy group, whereas no surgery was needed postoperatively in the phacotrabeculectomy group.</p><p><b>CONCLUSION</b>Phacotrabeculectomy and trabeculectomy treatments exhibit similar IOP reduction, successful rates, and complications when it comes to treating PACG patients with coexisting cataract, although additional surgery intervention may be needed for a few cases with cataract and complications after trabeculectomy.</p>

Rehabilitation of vision disorder and improved quality of life in patients with primary open angle glaucoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Primary open angle glaucoma (POAG) is a common cause of irreversible blindness. The variable etiology of POAG poses significant challenges for treatment and rehabilitation. We analyzed a large POAG patient cohort during treatment to reveal possible causes of vision disorder, assess vision-related quality of life (VRQL), and to evaluate the efficacy of rehabilitative treatments.</p><p><b>METHODS</b>We analyzed the visional disturbances in 500 POAG patients (890 eyes) by regular ophthalmic examination and visual field examination using Humphrey 30° perimetry. Appropriate rehabilitative treatments for POAG were prescribed based on results of clinical examination and included correction of ametropia, health education, counseling, and the fitting of typoscopes. VRQL was assessed before and after treatment by a VRQL self-assessment questionnaire.</p><p><b>RESULTS</b>Scores on the VRQL self-assessment were significantly lower compared to healthy controls. The primary cause of the vision disturbances was ametropia (97.99%), and 51.61% of the ametropia eyes had not received appropriate correction. The secondary causes of visual impairment were glaucomatous neurodegeneration (26.29%), complicated cataract, or other accompanying eye diseases. The causes of the clinical low vision (44 patients) were glaucomatous neurodegeneration (32 eyes), fundus diseases (23 eyes), keratopathy (11 eyes), and other eye diseases (10 eyes). The VRQL scores of patients improved significantly after rehabilitation and the correction of ametropia (P < 0.01). Twenty-five patients with low vision were provided with typoscopes, and 21 (84%) experienced significant functional recovery, while the remaining low vision patients could see letter lines two or more levels lower (smaller) on visual charts in a near vision test.</p><p><b>CONCLUSIONS</b>Vision disorders in POAG patients are common and severe. Appropriate rehabilitation, especially the correction of ametropia, can significantly improve VRQL as revealed by the self-assessment of POAG patients.</p>

Comparison of FP-7 and S-2 Ahmed glaucoma valve implantation in refractory glaucoma patients for short-term follow-up / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Ahmed glaucoma valves (AGV) has been used for decades, but there is no detailed report about the efficacy of AGV in Chinese glaucoma patients. This study aimed to compare the intraocular pressure (IOP) lowering efficacy and side effects of S-2 polypropylene and PF-7 silicone AGV implantation in Chinese refractory glaucoma patients.</p><p><b>METHODS</b>Patients were divided into S-2 model AGV group and FP-7 model AGV group. The complete and qualified surgical success rate, change of IOP, number of anti-glaucoma medications used and postoperative complications were recorded and analyzed.</p><p><b>RESULTS</b>Average follow-up time was comparable between two groups. IOP was reduced from (37.9 ± 12.7) mmHg preoperatively to (17.3 ± 5.3) mmHg at the last follow-up in S-2 group and reduced from (39.9 ± 14.4) mmHg to (17.7 ± 4.9) mmHg in FP-7 group. Anti-glaucoma medications were reduced from 3.8 ± 0.2 to 1.5 ± 0.2 in S-2 group, and 3.5 ± 0.2 to 0.7 ± 0.2 in FP-7 groups. The cumulative success rates were comparable in two groups, which were 61.2% and 72.1% in S-2 group and FP-7 group respectively. When IOP reduction criteria was used, complete success rates were 30.6% and 51.2% for S-2 and FP-7 groups, and qualified success rates were 86.1% and 92.7% separately. In both groups, the major complication was hypotony, and the previous trabeculectomy of patients was the major risk factor for surgery failure.</p><p><b>CONCLUSIONS</b>In this short-term retrospective study, S-2 AGV is showed at least as effective as FP-7 AGV in IOP reduction, but associated with higher rate of complications. Previous trabeculectomy is a principle risk factor for AGV implantation failure. These clinical outcomes are important for converting use of the FP-7 silicon AGV in Chinese refractory glaucoma patients.</p>

Clinical evidence in concurrence of retinitis pigmentosa and glaucoma / 中华医学杂志(英文版)

Glaucoma is rarely complicated by retinitis pigmentosa (RP). To provide clinical evidences for this rare situation, we report the concurrence of these two diseases in two children of a Chinese family. In the present two-child Chinese family without positive history, the older sister presented with bilateral sector RP and coexisting chronic angle-closure glaucoma, and the brother with bilateral whole RP but without coexisting glaucoma. Clinical evidences in concurrence of variants of RP and glaucoma because of possible different gene mutations from the same genetic background represent a rare situation, which may provide clues for future researches in molecular pathogenesis of these rare diseases.

Fifty-eight cases of ocular ischemic diseases caused by carotid artery stenosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The blood supply to the eye comes from the retinal central vascular system of the ophthalmic artery and the ciliary vascular system. The ophthalmic artery stems from the ipsilateral internal carotid artery. If occlusion or stenosis occurs in the carotid artery, the blood perfusion to the ophthalmic artery becomes insufficient, leading to signs and symptoms of anterior and posterior ocular ischemia. The objective of this study was to evaluate the clinical characteristics and risk factors of ocular ischemic diseases caused by carotid artery stenosis.</p><p><b>METHODS</b>This study was a retrospective review of 145 patients with carotid artery stenosis. Fifty-eight patients who had symptoms of ocular ischemic disease caused by carotid artery stenosis formed group A and the other 87 patients who only had carotid artery stenosis formed group B. We analyzed the causes and course of disease, and relative risk factors, by comparing the two groups.</p><p><b>RESULTS</b>The degree of carotid artery stenosis in group A was higher than that in group B. And group A had a greater decrease of ophthalmic artery flow. Male, hypertension, hyperlipidemia, and smoking were significantly related to carotid artery stenosis. Amaurosis fugax was the most common ocular symptom in group A. The ocular ischemic diseases mainly included ischemic optic neuropathy, central/branch retinal artery occlusion, ophthalmoplegia externa, and ocular ischemic syndrome.</p><p><b>CONCLUSIONS</b>Carotid artery stenosis correlates with ocular ischemic diseases. Ophthalmologists must observe for ocular symptoms, which were the onset symptoms in some patients.</p>

Expression of stromal cell-derived factor-1 in diabetic retinopathy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Neovascularization can cause vision loss in proliferative diabetic retinopathy (PDR) and may be affected by many factors. Stromal cell-derived factor-1 (SDF-1) is a potent stimulator of angiogenesis. The study was aimed to investigate the expression of SDF-1 and its correlation with vascular endothelial growth factor (VEGF) in the eyes with diabetic retinopathy.</p><p><b>METHODS</b>The levels of SDF-1 and VEGF were measured by enzyme-linked immunosorbent assay in the vitreous of 41 eyes of 41 patients with PDR and 12 eyes of 12 patients with idiopathic macular hole (IMH). Vitreous fluid samples and fibrovascular preretinal membranes were obtained at vitrectomy. SDF-1 and VEGF were localized using immunohistochemistry.</p><p><b>RESULTS</b>The vitreous concentration of VEGF was significantly higher in eyes with PDR ((2143.7 +/- 1685.21) pg/ml) than in eyes with IMH ((142.42 +/- 72.83) pg/ml, P < 0.001). The vitreous level of SDF-1 was also significantly higher in eyes with PDR ((306.37 +/- 134.25) pg/ml) than in eyes with IMH ((86.91 +/- 55.05) pg/ml, P < 0.001). The concentrations of both VEGF and SDF-1 were higher in eyes with active PDR than in eyes with inactive PDR. Panretinal photocoagulation (PRP) could decrease the SDF-1 levels in the vitreous of PDR patients. The vitreous concentration of SDF-1 correlated with that of VEGF in eyes with PDR (r = 0.61, P < 0.001). The costaining of SDF-1 and VEGF was confined to the vascular components in preretinal membranes.</p><p><b>CONCLUSIONS</b>SDF-1 protein is highly expressed in both the vitreous and preretinal membranes of PDR patients; SDF-1 may be correlated with VEGF in angiogenesis in PDR.</p>

Histological and ultrastructural study on the medial canthal ligament of blepharophimosis, ptosis and epicanthus inversus syndrome / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Blepharophimosis ptosis epicanthus inversus syndrome (BPES) is a rare congenital ophthalmic disorder, characterized by congenital eyelid malformation including bilateral ptosis, shortening of the horizontal eyelid fissure, epicanthus inversus, and increased distance between the inner canthi. In this research, we studied the histological structure and ultrastructure of medial canthal ligament of patients with BPES.</p><p><b>METHODS</b>Thirty patients with BPES who received plastic surgery at the Zhongshan Ophthalmic Center from March 2006 to January 2008 were studied. There were 17 males and 13 females with an average age of (8.73 +/- 3.37) years (3 - 31 years). The medial canthal ligaments of patients were collected during the plastic surgery to analyze the histological structure by hematoxylin and eosin (HE), Congo red, van Gieson's (VG), Masson trichrome and aldehyde-fuchsin staining. The ultrastructures of the medial canthal ligaments were also analyzed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Fifteen samples of medial canthal ligament from healthy persons with an average age of (9.02 +/- 3.12) years (6 - 30 years) were collected as a control group.</p><p><b>RESULTS</b>Morphological and histological study showed that the medial canthal ligaments of BPES patients were composed of collagen fibers, a few elastic fibers and striated muscles. The collagen fibers assemblies were disorganized and the fibrous connective tissues were undergoing hyaline degeneration. The karyopycnosis of fibroblasts was located among the collagen fibrils and the numbers of fibroblasts were decreased. Ultrastructural study with SEM showed that the collagen fibers were larger than normal, irregular and loose. Parts of the collagen fibers were broken and had a coarse surface. Ultrastructural study with TEM showed that the fibroblasts had less cytoplasm, fewer organelles and the nucleus displayed pyknosis.</p><p><b>CONCLUSIONS</b>The medial canthal ligament in BPES patients is composed chiefly of collagen fibers. The collagen fibers of medial canthal ligaments in BPES patients are disorganized and hyaline degeneration is present. The study revealed that the medial canthal ligament of BPES patients might have congenital dysplasia.</p>

Corticosteroid-induced severe glaucoma and posterior subcapsular cataract: a case report / 国际眼科杂志(Guoji Yanke Zazhi)

Corticosteroid-induced glaucoma (CIG) is a form of open angle glaucoma associated with both topical and systemic administration of corticosteroids. Here we described the clinical findings in a patient with severe glaucoma and posterior subcapsular cataract (PSC) after topical administration of corticosteroid eye drops. We concluded corticosteroid eye drop was an effective medicine for inflammation of the eyes; however,prolonged use could cause severe vision loss as a result of intractable corticosteroid-induced glaucoma and cataract.

Voltage-gated potassium channel Kv1.3 in rabbit ciliary epithelium regulates the membrane potential via coupling intracellular calcium / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The cell layer of the ciliary epithelium is responsible for aqueous humor secretion and maintenance. Ion channels play an important role in these processes. The main aim of this study was to determine whether the well-characterized members of the Kv1 family (Kv1.3) contribute to the Kv currents in ciliary epithelium.</p><p><b>METHODS</b>New Zealand White rabbits were maintained in a 12 hours light/dark cycle. Ciliary epithelium samples were isolated from the rabbits. We used Western blotting and immunocytochemistry to identify the expression and location of a voltage-gated potassium channel Kv1.3 in ciliary body epithelium. Membrane potential change after adding of Kv1.3 inhibitor margatoxin (MgTX) was observed with a fluorescence method.</p><p><b>RESULTS</b>Western blotting and immunocytochemical studies showed that the Kv1.3 protein expressed in pigment ciliary epithelium and nonpigment ciliary epithelium, however it seemed to express more in the apical membrane of the nonpigmented epithelial cells. One nmol/L margatoxin, a specific inhibitor of Kv1.3 channels caused depolarization of the cultured nonpigmented epithelium (NPE) membrane potential. The cytosolic calcium increased after NPE cell depolarization, this increase of cytosolic calcium was partially blocked by 12.5 micromol/L dantrolene and 10 micromol/L nifedipine. These observations suggest that Kv1.3 channels modulate ciliary epithelium potential and effect calcium dependent mechanisms.</p><p><b>CONCLUSION</b>Kv1.3 channels contribute to K+ efflux at the membrane of rabbit ciliary epithelium.</p>

Caspase-dependent retinal ganglion cell apoptosis in the rat model of acute diabetes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Neural apoptosis is generally believed to be mediated by two distinct pathways, caspase-dependant and caspase-independent pathways. This study investigated the apoptotic pathways involved in retinal ganglion cells in acute diabetes in rats.</p><p><b>METHODS</b>Diabetes was induced in male Wistar rats by a peritoneal injection of streptozotocin (STZ). Expression and localization of caspase-3 and apoptosis-inducing factor (AIF) proteins in the retina of diabetic rats was examined by Western blotting and immunohistochemistry analyses. Terminal transferase dUTP nick end labeling (TUNEL) assay and immunofluorescent staining specific for caspase-3 and AIF were applied to analyze for apoptosis of retinal ganglion cells. In addition, a caspase-3 inhibitor DEVD-CHO was injected intravitreally to further determine the apoptotic pathways of retinal ganglion cells triggered in acute diabetes.</p><p><b>RESULTS</b>Two weeks after induction of diabetes, a significant increase in caspase-3 protein expression and localization occurred in the nerve fiber layer, ganglion cell layer, and inner plexiform layer of the retina. Four weeks after the onset of diabetes, the increase in caspase-3 expression was profound eight weeks postinduction of diabetes (P < 0.05). Meanwhile, no AIF protein expression was detected in this study. In addition, intravitreal administration of the caspase-3 inhibitor DEVD-CHO reduced apoptosis of retinal ganglion cells by its direct inhibitory action on caspase-3.</p><p><b>CONCLUSION</b>Caspase-dependent apoptotic pathways may be the main stimulant of STZ-induced retinal ganglion cell apoptosis in acute diabetes.</p>

Analysis of MYOC gene mutation in a Chinese glaucoma family with primary open-angle glaucoma and primary congenital glaucoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Glaucoma is one of the leading causes of blindness in the world. Primary open-angle glaucoma (POAG) and primary congenital glaucoma (PCG) are subtypes of glaucoma. Myocillin is the first gene identified to be involved in POAG. Recently, myocillin mutation has been found in PCG. In this context, we reported a special glaucoma pedigree, which was composed of both PCG and POAG patients, and analyzed the mutation of myocillin in this pedigree.</p><p><b>METHODS</b>The family was composed of the parents, a son and a daughter. All members of the family underwent the complete ophthalmologic examinations. All coding exons 1 - 3 and flanking introns of myocilin gene were screened for sequence alterations by polymerase chain reaction and direct DNA sequencing.</p><p><b>RESULTS</b>The son was the proband, who was diagnosed as PCG in both eyes. The father was diagnosed as POAG in the right eye, the left eye was still normal. Both the sister and the mother of the proband had normal intraocular pressure without glaucomatous optic disc changes. The mutations in intron 2 of myocilin gene were detected in the family. While the proband and the father were homozygous, the mother and the sister were heterozygous for the mutation.</p><p><b>CONCLUSIONS</b>Homozygous mutation in intron 2 of myocilin gene is involved in both POAG and PCG. It is suggested that the pathogenesis might be overlapping in POAG and PCG.</p>