Traumatic dislocation of the iris into the vitreous cavity with intact lens: a case report.

BACKGROUND: Traumatic aniridia occurs when the iris is extruded from the eye and is often accompanied by lens injuries. However, traumatic aniridia due to dislocation of the iris into the vitreous cavity without lens damage has never been reported. CASE PRESENTATION: A 30-year-old man presented with visual loss and pain for 6 h after a thin wire injured his right eyeball. Ophthalmologic examinations manifested a 2 mm full-thickness corneal laceration and total hyphema. An intact clear lens, healthy attached retina, and almost complete iris tissue in the vitreous cavity were found after resolution of hyphema the next day. Further examination revealed that the defect in the zonule below the corneal wound was the path for the iris to enter the vitreous cavity. The patient opted for nonsurgical treatment until pigment granules and opacity were observed in the vitreous cavity after 50 days. Vitrectomy was performed to remove the dislocated iris. CONCLUSIONS: The presentation of this unique case indicates that the torn iris was displaced to the vitreous cavity with an intact lens and missing local zonula instead of out the corneal laceration after a penetrating injury. The type of injury, mechanism, and force on the spot may contribute to the occurrence of this rare condition. Instead of artificial irises, tinted glasses were more appropriate treatment option for this patient. Peripheral retinal examination was essential in the management of this case. In such cases, the iris in the vitreous cavity should be resected to prevent complications.

A new perspective for analyzing clinical characteristics of idiopathic retinal vasculitis, aneurysms, and neuroretinitis syndrome.

PURPOSE: We aimed to analyze the clinical characteristics of idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome. Furthermore, we aimed to correlate the number and location of retinal aneurysms with the size of retinal non-perfusion area and neovascularization. METHODS: Six patients with IRVAN syndrome (1 male and 5 females, age 5-38 years) were enrolled in this study. Fundus fluorescein angiography (FFA) was used to determine the total number of retinal aneurysms, number of aneurysms within the first branch of the retinal artery, minimum distance between the non-perfusion margin and the optic disc, and the number of retinal aneurysms in each quadrant, as well as the type of neovascularization. RESULTS: The size of the non-perfusion area was positively correlated with the total number of retinal aneurysms, the number of aneurysms within the first branch of the retinal artery, and the number of retinal aneurysms in each quadrant (P < 0.05). During the 5-year follow-up, one patient exhibited a dynamic change in the number and location of retinal aneurysms. CONCLUSIONS: In IRVAN syndrome, the number and location of retinal aneurysms correlate with the size of retinal non-perfusion area and type of neovascularization.

A novel mutation in the VHL gene in a Chinese family with von Hippel-Lindau disease.

BACKGROUND: Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited cancer syndrome, and VHL is identified as a tumor suppressor gene. The main objective of this study was to identify disease-causing mutations in a Chinese family affected with VHL disease. METHODS: Genomic DNA was extracted from peripheral blood from a Chinese family with VHL. A predicted pathogenic variant was identified by targeted exome capture technology and next-generation sequencing. RESULTS: A novel heterozygous mutation (c.349 T > A, p.W117R) was detected in affected family members. No mutation was detected in unaffected family members or in the 150 normal controls. The mutation segregated with the disease phenotype throughout three generations. Histopathological examination revealed the characteristics of hemangioblastoma. CONCLUSIONS: A novel W117R was detected in the VHL gene that caused retinal hemangioblastomas in affected members of a Chinese family.

Early Diagnosis of Recurrent Optic Neuritis Using Contrast-Enhanced T2 Fluid-attenuated Inversion Recovery Imaging: a Case Report.

The diagnosis of the recurrent optic neuritis is commonly established clinically, and sometimes it could be challenging because the involved optic nerve does not always show significant enhancement on conventional contrast enhanced-T1 weighted imaging (CE-T1WI). In this paper, we reported a middle-aged female with early diagnosis of recurrent optic neuritis using contrast-enhanced T2 fluid-attenuated inversion recovery imaging (CE-T2FLAIR). The involved optic nerve presented evident enhancement on CE-T2FLAIR and no enhancement on CE-T1WI. This case suggested that the CE-T2FLAIR may be a useful diagnostic tool specifically for the recurrent optic neuritis in clinical practice.

Characterization of macular thickness changes in Leber's hereditary optic neuropathy by optical coherence tomography.

BACKGROUND: To characterize macular thickness (MT) changes in Leber's hereditary optic neuropathy (LHON) patients by cirrus HD-optical coherence tomography (OCT), and to study the correlation between MT and best corrected visual acuity (BCVA). METHODS: Fifty-two eyes from 52 consecutive LHON patients and 14 eyes from 14 age- and sex-matched healthy controls were scanned by OCT. Affected eyes were classified into five groups according to disease duration (1st group: ≤3 months; 2nd group: 3-6 months; 3rd group: 6-9 months; 4th group: 9-12 months; and 5th group: >12 months). MT was compared and analyzed. The correlation between BCVA and MT was calculated. RESULTS: Less than six months after LHON onset, the cube average thickness (CAT) and the MT in the superior, nasal, inferior, and temporal quadrants of the inner ring and the MT in the nasal quadrant of the outer ring were decreased (P < 0.005); at 3-6 months onset, the MT of the temporal quadrants of the outer ring was decreased (P = 0.045); after 6 months, the MT was significantly thinner in all measurements (P < 0.01) except for the central ring. The BCVA was significantly different between each group and controls (P < 0.05), but there was no significant correlation among the five groups (P = 0.666). There was no significant correlation between the BCVA and CAT (P = 0.893). CONCLUSIONS: The MT thinned before the retinal nerve fiber layer and this occurred with a particular sequence. Our results provide potential diagnostic information for LHON.

Analysis of Phenotypes Associated with Deficiency of PAX6 Haplotypes in Chinese Aniridia Families.

OBJECTIVE: To examine the clinical phenotype and genetic deficiencies present in Chinese aniridia families with PAX6 haplotype deficiency. METHODS: A comprehensive questionnaire and ophthalmological assessments were administered to both affected patients and unaffected relatives. The clinical feature analysis included the evaluation of visual acuity, intraocular pressure, slit-lamp anterior segment examination, fundus photography, and spectral domain optical coherence tomography. To identify the mutation responsible for aniridia, targeted next-generation sequencing was used as a beneficial technique. RESULTS: A total of 4 mutations were identified, consisting of two novel frameshift mutations (c.314delA, p.K105Sfs*33 and c.838_845dup AACACACC, p.S283Tfs*85), along with two recurring nonsense mutations (c.307C>T, p.R103X and c.619A>T, p.K207*). Complete iris absence, macular foveal hypoplasia, and nystagmus were consistent in these PAX6 haplotype-deficient Chinese aniridia families, while corneal lesions, cataracts, and glaucoma exhibited heterogeneity both among the families and within the same family. CONCLUSION: In our study, two novel PAX6 mutations associated with aniridia were identified in Chinese families, which expanded the phenotypic and genotypic spectrum of PAX6 mutations. We also analyzed the clinical characteristics of PAX6 haplotype deficiency in Chinese aniridia families.

[Clinical characteristics of paraneoplastic retinopathy and optic neuropathy].

OBJECTIVE: To analyze the clinical characteristics of paraneoplastic retinopathy and optic neuropathy(PRON). METHODS: Case series study. Eight patients were enrolled from October 2006 to March 2012 visited in ophthalmology department, the People Liberation Army General Hospital. The patients were underwent a series of examinations, including fundus photography, visual electrophysiology, fundus fluorescein angiography, optic coherent tomography,fundus autofluorescent imaging, perimetry, ultrasonography, magnetic resonance imaging, spinal tap and cerebrospinal fluid test, paraneoplastic syndrome (PNS) antibody test. The patients were followed up in outpatient department and(or) by phone. The clinical manifestation,entity types, and treatment were analyzed. RESULTS: Of the eight patients, there were cancer associated retinopathy(CAR) 3 cases, bilateral diffuse uveal melanocytic proliferation (BDUMP) 2 cases and paraneoplastic optic neuropathy(PON) 3 cases. Five patients were detected the PNS antibodies and revealed three patients with positive results. As for the primary malignancy,four of the eight patients were lung carcinoma,others included invasive thymoma, kidney cancer, acute lymphocytic leukemia and cervical cancer, each for one case. All the patients complained vision blurring or progressive visual decrease. Other complaints included dark shadow in two patients, shimmering, dazzling, double vision and eye pain, each in one patient. One patient complained progressive decreased vision in both eyes prior to the diagnosis of lung cancer. Of the 16 eyes of the eight patients, there were six patients with no light perception vision, five from light perception to 0.05, and other five with no less than 0.4 vision, in the end of the follow up. Five patients were treated with steroid with unsatisfactory efficacy. CONCLUSIONS: Each entity of PRON has its own clinical characteristics. PRON especially BDUMP may be a pre-metastatic disease.

[Meta analysis of acupuncture in the treatment of optic atrophy].

OBJECTIVE: To evaluate the efficacy and safety of acupuncture for optic atrophy. METHODS: All the randomized controlled trials (RCTs) on optic atrophy treatment with acupuncture were included after retrieving the PubMed, Embase, Cochrane Library, CBM, CNKI, VIP, Wanfang database from their establishment to November 2012. The bibliographies of the included studies were retrieved as well. The quality of RCTs meeting the inclusion criteria was evaluated and the data were extracted. Meta-analyses were performed with Stata 11.2 software. RESULTS: Thirteen RCTs involving 1180 eyes were included. Meta-analyses showed that the effect of acupuncture or combined with medicine was superior to medicine alone in terms of total effectiveness [OR=3.281, 95% CI ( 2.517, 4.278)], visual acuity [3.287, 95% CI (2.193, 4.925)], and visual field [3.215, 95% CI (1.580, 6.543)]. The visual sensitivity and P-VEP test showed the similar results. CONCLUSION: Acupuncture is superior to medicine in terms of improved visual acuity, visual field and P-VEP. However, large samples, and high-quality studies are needed for stronger evidence.

Cone Density Distribution and Related Factors in Patients Receiving Hydroxychloroquine Treatment.

Purpose: Hydroxychloroquine is an effective treatment for rheumatic diseases; however, retinal damage is a possible side effect. We aimed to identify the retinal area and related risk factors associated with cone density reduction caused by hydroxychloroquine. Methods: We recorded the retinal images of patients with rheumatic diseases taking hydroxychloroquine (n = 44) and compared them with images of healthy controls (n = 107). Cone density was obtained in vertical and horizontal axes. Regions of decreased cone density and associations between age, rheumatic disease type, dosage for ideal body weight, and cone density were evaluated. Results: Cone densities were significantly lower in hydroxychloroquine-treated patients than in sex- and age-matched controls in the vertical axis (P < 0.001), with no significant difference in the horizontal axis (P = 0.120); in healthy elderly than in healthy young people in the horizontal axis (P < 0.001), with no significant difference in the vertical axis (P = 0.100); in hydroxychloroquine-treated elderly than in hydroxychloroquine-treated young patients in both axes (both P < 0.05); among patients with different rheumatic disease types, with no significant difference in the vertical axis (P = 0.294). The daily dose was negatively correlated with cone density in the vertical axis and inferior quadrant. Conclusions: Hydroxychloroquine reduces retinal cone cell density in the vertical axis. Cone density loss in the horizontal axis increases with age; further, hydroxychloroquine dosage is negatively correlated with cone density in the vertical axis and inferior quadrant. Early screening of hydroxychloroquine-related retinal injury should consider changes in cone density in the vertical axis.

The Evaluation of the Maculopathy Using Dynamic Contrast-enhanced MRI in Patients with Proliferative Diabetic Retinopathy.

BACKGROUND: Dynamic Contrast-enhanced Magnetic Resonance Imaging (DCE-MRI) technique could not only quantify blood-retinal barrier (BRB) breakdown leading to macular edema associated with diabetes, but also provide a two-dimensional imaging method that is not interfered by refracting media. OBJECTIVE: The current study was aimed to evaluate the macular change in the patients with diabetic retinopathy using DCE-MRI technique. METHODS: Twenty patients with Diabetic Retinopathy (DR) and 20 Normal Controls (NC) were included. The fast spoiled gradient echo sequence was used to perform dynamic contrast T1WI enhancement on 3.0T MR system. The macular region, optic papila and nasal retina were performed with quantitative DCE-MRI evaluation using Omni-Kinetics software. RESULTS: The maximal concentration, the area under the concentration-time curve (AUCconcentration-time) and maximal slope of macular region were significantly higher in DR [0.270(0.03,1.20)mmol/ 100ml, 2.71(0.04,9.91) mmol*min and 0.38(0.06,3.18) mmol/min, respectively] than that [0.169(0.03,0.72) mmol/1.25(0.13,10.41) mmol*min and 0.245(0.06,1.34) mmol/min] in NC (U value = 515.00 and P value = 0.080, U value = 433.00 and P value = 0.000, and U value = 563.00 and P value = 0.023, respectively). The receiver operating characteristic curve (ROC) analysis demonstrated that the area under AUCconcentration-time was 0.729±0.058 with the cut-off value 1.479 mmol*min (sensitivity 80.00% and specificity 62.50%) for macular region. CONCLUSION: The quantitative DCE-MRI technique could be used to evaluate the maculopathy associated with diabetic retinopathy.

Various phenotypes of autosomal dominant cone-rod dystrophy with cone-rod homeobox mutation in two Chinese families.

AIM: To present the clinical manifestations of 5 autosomal dominant cone-rod dystrophy (adCORD) patients from two Chinese families with cone-rod homeobox (CRX) mutation (p.R41W), and to explore the clinical heterogeneity of adCORD with CRX mutation (p.R41W). METHODS: Interrogation and ophthalmological examinations were undertaken in all patients and unaffected members. Analysis of clinical features was performed by visual acuity, slit lamp examination, visual field examination, fundoscopy, autofluorescence and spectral domain optical coherence tomography. Targeted next-generation sequencing was applied as a useful tool to identify the causative mutation of CORD genes. RESULTS: A CRX missense mutation c.121C>T was identified in all patients, resulting in an amino acid change from arginine acid to tryptophan (p.R41W). The patients presented with early onset, progressive and different severities with CORD. CONCLUSION: This is the first report of the clinical phenotype of CRX mutation (p.R41W) in Chinese families, and the mutation can lead to a wide range of various retinal phenotypes.

Novel mutations in the BEST1 gene cause distinct retinopathies in two Chinese families.

AIM: To describe the clinical heterogeneity of patients with novel mutations in BEST1. METHODS: All the members in the two Chinese families underwent detailed clinical evaluations including best-corrected visual acuity, slit-lamp examination, applanation tonometry, and dilated fundus examination. Fundus autofluorescence, fundus fluorescein angiography, spectral-domain optical coherence tomography, electrooculography, and electroretinogram were also performed. Genomic DNA was extracted from venous blood for all the participants. The targeted next-generation sequencing of inherited retinal disease-associated genes was conducted to identify the causative mutation. RESULTS: A novel BEST1 missense mutation c.41T>C (p.Leu14Ser) was identified in Family 1. It was co-segregated with the phenotype of best vitelliform macular dystrophy (BVMD) and bioinformatics analysis confirmed it was harmful. Another novel BEST1 frameshift mutation c.345_346insGGCAAGGACG (p.Glu119Glyfs*116) and a novel USH2A missense mutation c.12560G>A, p.Arg4187His were identified in family 2 with retinitis pigmentosa (RP), which might interact and lead to the phenotype of RP. CONCLUSION: Two novel mutations in the BEST1 gene in two unrelated families with distinct phenotypes and BEST1 mutation accompanied with USH2A mutation would result in RP, which could be enormously helpful in understanding the pathogenesis of the inherited retinal disease caused by a BEST1 mutation.

WFS1-Associated Optic Neuropathy: Genotype-Phenotype Correlations and Disease Progression.

OBJECTIVE: To evaluate the pattern of vision loss and genotype-phenotype correlations in WFS1-associated optic neuropathy (WON). DESIGN: Multicenter cohort study. METHODS: The study involved 37 patients with WON carrying pathogenic or candidate pathogenic WFS1 variants. Genetic and clinical data were retrieved from the medical records. Thirteen patients underwent additional comprehensive ophthalmologic assessment. Deep phenotyping involved visual electrophysiology and advanced psychophysical testing with a complementary metabolomic study. MAIN OUTCOME MEASURES: WFS1 variants, functional and structural optic nerve and retinal parameters, and metabolomic profile. RESULTS: Twenty-two recessive and 5 dominant WFS1 variants were identified. Four variants were novel. All WFS1 variants caused loss of macular retinal ganglion cells (RGCs) as assessed by optical coherence tomography (OCT) and visual electrophysiology. Advanced psychophysical testing indicated involvement of the major RGC subpopulations. Modeling of vision loss showed an accelerated rate of deterioration with increasing age. Dominant WFS1 variants were associated with abnormal reflectivity of the outer plexiform layer (OPL) on OCT imaging. The dominant variants tended to cause less severe vision loss compared with recessive WFS1 variants, which resulted in more variable phenotypes ranging from isolated WON to severe multisystem disease depending on the WFS1 alleles. The metabolomic profile included markers seen in other neurodegenerative diseases and type 1 diabetes mellitus. CONCLUSIONS: WFS1 variants result in heterogenous phenotypes influenced by the mode of inheritance and the disease-causing alleles. Biallelic WFS1 variants cause more variable, but generally more severe, vision and RGC loss compared with heterozygous variants. Abnormal cleftlike lamination of the OPL is a distinctive OCT feature that strongly points toward dominant WON.

[Outcome after treatment of myopia with implantable Collamer lens].

OBJECTIVE: To evaluate the efficacy, predictability, stability, and safety of the surgical correction myopia using implantable Collamer lenses (ICL) in phakic eyes. METHODS: A prospective study was performed to analyze 91 eyes of 48 patients who had the implantation of ICL for the treatment of myopia from July 2008 to February 2010. Patients were examined preoperatively and followed at 1 week, 1, 3, 6, and 12 months postoperatively. The examinations included the uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), refraction, contrast sensitivity, wavefront aberration, intraocular pressure, space between crystal lens and intraocular lens (vault), endothelial cell density (ECD), anterior chamber depth (ACD), surgical complication, etc. RESULTS: Successful implantation was achieved in all patients. The mean follow-up time was (9.54 ± 4.12) months (SD)(range 1 to 12 months). The mean preoperative SE was -12.38 diopters (D) (range -5.0D to -23.0D). Postoperatively, UCVA was maintained or improved in all eyes. UCVA achieved 1.0 in 58 eyes (64%) and BCVA gained more than 1 line in 69 eyes (75.9%). The glare and no glare contrast sensitivity were improved at 3cd, 12cd and 18cd, with the exception of 6cd. The aberration decreased in RMS, spherical and coma. Post operative ACD (1 week after operation) diminished 8.92% as compared with the preoperative ACD. The mean vaulting was (452 ± 216.38) µm (6 months) and ranged 130 - 1080 µm at different follow-up periods. There was no statistically significant difference in vaulting between postoperative data at different periods (t = 0.200, P > 0.05). The mean postoperative ECD decreased but had no statistically difference compared with the preoperative ECD. ACD decreased 31% after surgery in 2 eyes (2.1%). Transient high IOP was observed in 13 eyes (2.1%) one week after the operation. CONCLUSION: These results indicate that ICL implantation in the treatment of myopia is efficient, predictable, safe, and reliable.

[Clinical investigation on anterior capsule preservation in surgical management for severe proliferative diabetic retinopathy].

OBJECTIVE: To report the outcomes of patients treated with the anterior capsule preservation technique used in surgical management for severe proliferative diabetic retinopathy. METHODS: Anterior capsule was preserved following pars plana lensectomy or fragmentation during vitrectomy for cataract patients with proliferative diabetic retinopathy, all eyes presented tractional and tractional/rhegmatogenous retinal detachment and involvement of posterior retina. Postoperatively, the transparency of anterior capsule was classified into A, B, C and D degrees according to the photographic record. The outcomes of visual acuity, retinal reattachment, intraocular pressure and the complications related to the operation as well as their managements were analyzed. RESULTS: Vitrectomy, silicone oil tamponade and anterior capsule preservation were performed in 58 eyes. The transparency of the anterior capsule in these eyes was degree A in 26 eyes (44.8%); degree B in 20 eyes (34.5%); degree C in 7 eyes (12.1%) and degree D in 5 eyes (8.6%). Forty eyes (79.3%) had a postoperative best corrected visual acuity > or = 0.05, 21 eyes received secondary intraocular lens implantation. Finally, 7 eyes were classified to be silicone oil-depended eyes because of severe proliferative changes occurred and the presence of macular hole. Complications related to the operation included iris mal-cut in 1 eye, silicone oil escaped into anterior chamber in 7 eyes, iris neovascularization and new vascular glaucoma in 1 eye respectively, intraocular pressure elevation in 4 eyes, secondary pre-macular membrane formation in 11 eyes and macular hole in 2 eyes. CONCLUSIONS: The anterior capsule preservation procedure and selective secondary intraocular lens implantation is an acceptable method in surgical management for severe proliferative diabetic retinopathy. The main causes of the opacification of anterior capsule are the proliferation of residual lens epithelial cells and blood deposit on the posterior surface. Silicone oil escaped into the anterior chamber is one of the most common complications related to this procedure.

A novel mutation of FOXC1 in a Chinese family with Axenfeld-Rieger syndrome.

Axenfeld-Rieger syndrome (ARS) is a disorder affecting the anterior segment of the eye and causing systemic malformations, and follows an autosomal-dominant inheritance pattern. The aim of the present study was to identify the underlying cause of ARS in a Chinese family. Genomic DNA was extracted from the peripheral blood of the subjects from a family with ARS. The pathogenic variant was identified by targeted next-generation sequencing and confirmed by Sanger sequencing. A novel heterozygous mutation of the forkhead box (FOX)C1 gene (c.1494delG, p.G499Afs*20) was detected in all affected members of the family, while no mutation was identified in the unaffected members or in the 150 normal controls. The affected members exhibited typical ocular and craniofacial anomalies. The results of the present study demonstrated that a novel deletion in exon 1 of the FOXC1 gene caused ARS in this Chinese family.

Novel compound heterozygous mutation in the POC1B gene underlie peripheral cone dystrophy in a Chinese family.

PURPOSE: To describe the clinical characteristics of a Chinese family with peripheral cone dystrophy (PCD) and identify the gene mutations causing PCD. METHODS: The Chinese PCD pedigree underwent comprehensive ophthalmic examinations, including visual acuity, slit lamp examination, fundoscopy, visual field examination, autofluorescence, fluorescence fundus angiography and indocyanine green angiography, full-field electroretinograms, and spectral-domain optical coherence tomography. The targeted next-generation sequencing of COD or cone-rod dystrophy (CORD) genes was used to identify the causative mutation. RESULT: The fundus characteristics of the Chinese patient were consistent with PCD. The novel compound heterozygous mutation, c.1354C>T and c.710A>G, in POC1B was identified in the patient, the mutations were segregated with the PCD phenotype in the family and were absent from ethnically matched control chromosomes. Prediction analysis demonstrated the novel missense mutation, POC1B c.710A>G, might be damaging. CONCLUSIONS: PCD was a type of COD or CORD and the novel compound heterozygous mutation in POC1B was responsible for PCD phenotype in the family.

Recombination and identification of human alpha B-crystallin.

AIM: To recombine the human alpha B-crystallin (αB-crystallin) using gene cloning technology and prokaryotic expression vector and confirm the biological activity of recombinant human αB-crystallin. METHODS: Cloning the human αB-crystallin cDNA according to the nucleotide sequence of the human αB-crystallin, constructing the pET-28/CRYAB prokaryotic expression plasmid by restriction enzyme digestion method, and stably expressing transformed into the Escherichia coli (E. coli) DH5 alpha. The recombinant human αB-crystallin was purified by Q sepharose. By enzyme digestion analysis, Western blotting and sequencing, the recombinant human αB-crystallin was identified and the activity of its molecular protein was detected. RESULTS: Compared with the gene bank (GeneBank), the cloned human sequence of human αB-crystallin cDNA has the same open reading frame. Identification and sequencing of the cloned human αB-crystallin cDNA in prokaryotic expression vector confirmed the full length sequence, and the vector was constructed successfully. The E. coli containing plasmid pET-28/CRYAB induced by isopropyl-ß-D-thiogalactoside successfully expressed the human αB-crystallin. Insulin confirmed that the recombinant human αB-crystallin has a molecular chaperone activity. CONCLUSION: The prokaryotic expression vector pET-28/CRYAB of recombinant human αB-crystallin is successfully constructed, and the recombinant human αB-crystallin with molecular chaperone activity is obtained, which lay a foundation for the research and application of the recombinant human αB-crystallin and its chaperone activity.

[Regeneration of optic nerve fibers following graded injuries in rats].

OBJECTIVE: To investigate the changes of retinal ganglion cell (RGC) and their axons, and nerve regeneration ability following graded optic nerve injury (ONI) in rats. METHODS: A pair of cross-action forceps with 148.0 g clipping pressure was used to clip rat optic nerves for 3, 6, 12, 30 and 60 s to induce graded ONI animal model. The RGC was counted at 0.5, 1, 2, 3 and 7 months and the axons were observed 1, 2 and 3 months post-injury. The regeneration process was observed by transmission electron microscopy. The number of optic nerve fibers in transverse sections was calculated in silver-stained longitudinal sections, and a regeneration index (RI) was calculated based on these numbers. The RI, reflecting the regeneration ability of injured optic nerves, was calculated as follows: (number of nerve fibers 0.5 mm behind injury site-number of nerve fibers 2.5 mm behind injury site)/(number of nerve fibers 0.5 mm retrobulbarly-number of nerve fibers 2.5 mm behind injury site). RESULTS: RGC and axons lost continuously after partial ONI. The loss of RGC was fitted with exponential pattern consisted of two phases, acute losing phase within first two weeks post injury and followed by another phase characterized by slowly reducing of RGC. The loss ratio of RGC increased and the survival ratio decreased with the severity of injury intensity. The loss of RGC and axons was aggregated in severe injury and showed a self-limited trend in mild injury. A large amount of clustered, zonal unmyelinated regeneration fibers were present after injury. The RI was 1.409, 1.490, 0.916, 1.119 and 1.224 following 3, 6, 12, 30 and 60 s clipping injury (chi2 = 281.2, P < 0.01), respectively. Different RI was associated to different injury intensity, with a greater regeneration ability in mild injury. CONCLUSIONS: The secondary reaction and regeneration ability vary with graded intensity of optic nerve injury. A self-limited secondary reaction and a more powerful regeneration ability are associated with a mild injury. The repair behavior and the injury may reach a balance and result in a successful regeneration after a certain degree of injury.

Calibration and standardisation of graded optic nerve injuries in rats.

OBJECTIVES: To calibrate and standardise an animal model of graded optic nerve injury (ONI) in rats to facilitate future inter-laboratory data comparisons, focussing on quantification of injury intensity, injury severity, and the correlation between them. METHODS: A pair of cross-action forceps or a pair of artery clips was used to induce optic nerve (ON) crush injuries. A lever principle and a simplified method were used to measure the crushing force. The simplified method directly measured weights as an external force exerted on the tip of the forceps or clips, which was just sufficient to maintain a gap and was equivalent to the closing (crush) force. The impulse and averaged impulse were explored as physical quantities to compare injury intensities. Graded ONIs were made by crushing the ON for 3, 6, 12, 30 or 60 seconds by the cross-action forceps, or 5, 10 or 15 seconds by the artery clips. The injury severity was evaluated by counting surviving retinal ganglion cell (RGC) through applied FluoroGold to the superior colliculus and lateral geniculate body before ON crush, intact RGC counting by applied FluoroGold after ON crush, and ON axon counting. RESULTS: Similar results were obtained by the lever principle method and the simplified method. The crushing force of the cross-action forceps and the artery clips was 148.0 gram force (gf) and 32.4 gf, respectively. The graded ONI animal models were successfully created in rats without retinal ischaemia post-trauma. The averaged impulse produced by the artery clips for 15 seconds was equal to that produced by a 3-second crush of the cross-action forceps. The correlation between injury intensity and injury severity was fitted for a power function. DISCUSSION: Our results provide a simplified and effective means to quantify and analyse data from ON crush studies compared with previously reported animal models.