The human hereditary retinal degeneration is one of the main cause of irreversible blindness in the world. the mechanisms leading to retinal photoreceptor degeneration are not entirely clear. However, microglia acting as innate immune monitors are found to be activated early in retinal degeneration in many retinitis pigmentosa animal models. These activated microglia are involved in phagocyte rod cell fragments of degenerated retina, and also produce high levels of cytotoxic substances such as pro-inflammatory cytokines and chemokines, which aggravate the death of adjacent healthy photoreceptor cells. It suggests that microglia activation plays an important role in photoreceptor degeneration. At the same time, a series of studies have confirmed that some drugs can prevent or reduce neuronal death and slow the occurrence and progression of retinal degeneration by interfering with abnormal activation of microglia. It is expected to be a new choice for the treatment of hereditary retinal degeneration.
Objective To investigate the clinical characteristics and mechanisms of ocular manifestations related to carotid artery stenosis. Methods The general clinic data and related ocular manifestations in 124 patients with carotid artery stenosis were retrospectively. Results In the 124 patients, 36 (29%) had ocular manifestations, and 28 (22. 6 %) complained the ocular discomfort as the first symptom. Among the 36 patients, 31 patients (86.1%) had been disclosed unilateral or double stenosis of internal carotid artery by carotid Doppler ultrasound examination, and the result of digital subtract angiography revealed middle and severe degree of internal carotid artery stenosis in 8 and 23 patients respectively. There was no statistic difference of incidence of ocular manifestations between 67 patients of severe internal carotid artery stenosis and 34 patients with middle one（chi;２test,P =0.266 2，P＞0.05). The ocular manifestations included amaurosis fugax (52.8%),acute decline or loss of the visual ability and defect of visual fields (36.1%), binocular diplopia (13.9%), ptosis (13.9%), and persistent high intraocular pressure(2.8%) one patient might had several ocular manifestations simultaneously. In 36 patients, central retinal artery occlusion had been diagnosed in 4, venous stasis retinopathy in 1,central or branch retinal vein occlusion in 6, neovascular glaucoma in 1, and anterior ischemic opticneuropathy in 2. One patient with double occlusion of internal carotid artery didnrsquo;t have any ocular manifestation. Conclusion Carotid artery stenosis, especially internal carotid artery may lead to acute or chronic ocular ischemic lesions, and the occurrence of ocular manifestations in chronic ocular ischemic lesions relates to compensa tion of collateral circulation；patients with ocular ischemic lesions are recomm end to undergo a routine carotid artery examination. (Chin J Ocul Fundus Dis, 2006,22:376-378)
Objective To explore the ocular clinical features in patients with cranial venous sinus thrombosis (CVST). Methods The clinical data from 118 inpatients with CVST diagnosed by digital subtraction angiography (DSA).The patients included 53 males and 65 females with the sexual rate of1 :1.2. The initial onset age of the patients ranged from 15 to 67; 20-45 are the most common onset ages, and 30-40 reached the peak. The CVST patients were divided into 3 groups a c cording to the onset styles, including acute onset (within 2 days), subacute ons et (2 days to 1 month), and chronic onset (more than 1 month). The features of o cular and systemic manifestations was analyzed. A total of 58 out of 118 patient s with CVST were followed up for about 1 year after the diagnosis and treatment. Results Among the 118 patients with CVST, 25 (21.2%) had the ocular symptoms as the initial onset, 36 (305%) had ocular syndrome with other symptoms, and 57 (48.3%) had non ocular symptoms. There was no statistical significance among each group. The most common chief complains were the blurred and decreased vision (in 61 eyes, occupying 85.9% of all the chief complains). The most common symptom was papilloedema (in 57 eyes, accounting for 48.3% of all the patients with CVST). In 58 follow-up patients, 13 (22.4%) had serious visual decrease due to the optic atrophy. All the ocular manifestations related to the intracranial hyper tension caused by CVST. Conclusions In patients with CVST, 1/3 have ocular symptoms, and 1/5 have ocular symptoms as the initial manifestation. Visual decrease and papilloedema are the common symptoms in patients with CVST. We should especially advert to the patients with intracranial hypertension with unknown origins. (Chin J Ocul Fundus,dis,2006,22:373-375)
Objective To observe the clinical features, phenotypes and genotypes in a Chinese family with choroideremia (CHM). Methods A Chinese four-generation family (15 members) with CHM, including 5 patients (4 males/1 female), 2 female carriers and 8 healthy members, was enrolled in this study. Initially all family members underwent best corrected visual acuity (BCVA), indirect ophthalmoscopy, fundus fluorescein angiography, optical coherence tomography (OCT), visual field and full view electroretinogram (ERG). BCVA was followed up for 3 years. Venous blood samples were collected, and all of the 15 coding exons and flanking intron regions were amplified in the proband by polymerase chain reaction followed by direct sequencing. Protein structure was modeled based on the protein data bank and mutations in DeepView v4.0.1 to predict the effect of the mutations. A total of 180 healthy volunteers were enrolled as control group to matching CHM gene sequences. Results The visual acuity (VA) of 3/4 adult male patients began to decrease at less than 10, 10 and 30 years old, the average BCVA was 0.43. There were characteristic signs and symptoms of CHM including narrow visual field, extinguished rod and cone response in ERG, disappeared junction line and intermediate line of photoreceptor inner segment/outer segment on OCT. After 3 years, the mean BCVA decreased to 0.11. The BCVA of one young male patient was 1.0 in both eyes with minor changes fundus and visual field. The VA of the female patient began to decrease at 50 years old, her BCVA of two eyes were 0.5 and 0.25, respectively. The fundus changes were typical of CHM, with relative scotomas in the peripheral visual field of OD, and big scotomas in the OS. After 3 years, her mean BCVA decreased to 0.2. Of 2 female carriers, one had minor fundus changes (patches of pigmentary deposits, atrophy spots of retinal pigment epithelium cells), and the other was normal. A novel heterozygous c.1837G＞A mutation in exon 15 of CHM was detected in the proband, which resulted in the substitution of serine by proline at codon 613 (p.D613N). Based on molecular modeling, the misfolded protein caused by the mutation might destabilize the structure of the helix that potentially could affect the global stability of the Rep-1 protein. Conclusions A novel c.1837G＞A (p.D613N) mutation may be the causative mutation for CHM in this family. Female CHM carriers may have some signs and symptoms.
ObjectiveTo determine the pathogenic gene mutation in a family with incomplete congenital quiescent night blindness (CSNB) of Schubert-Bornschein type. MethodsA retrospective clinical study. In February 2021, one patient and his parents and elder brother from a Han Chinese incomplete CSNB of Schubert-Bornschein type family diagnosed by clinical and genetic examination at Henan Provincial People's Hospital were included in the study. The patient’s medical history, family history were inquired; best corrected visual acuity (BCVA), color vision, fundus color photography, full-field electroretinogram (ERG), and frequency domain optical coherence tomography (OCT) were examined in detail. Five ml of the subject’s peripheral venous blood was collected and the whole genome DNA was extracted. The genomic DNA of the subject was library constructed, and all-exon probes were polymerized for capture. The suspected pathogenic mutation site was verified by Sanger, and the pathogenicity of the gene mutation site was determined by parallel bioinformatics analysis. ResultsThe BCVA of both eyes of the proband (Ⅱ2) was 0.4; the color vision test could not recognize the red color. Fundus examination showed no obvious abnormalities. The retina thickness in the macular area of both eyes was slightly thinned. ERG examination of the whole field showed that the amplitude of ERG b wave was significantly reduced under the stimulation of binocular dark adaptation 3.0 and showed a negative waveform. The mother of the proband (Ⅰ2) had normal BCVA, color vision, fundus color photography, and frequency domain OCT examination. The full-field ERG examination showed that the amplitude of each eye reaction was slightly reduced, and the amplitude of the dark adaptation shock potential was significantly reduced. Genetic testing showed that the proband (Ⅱ2) had a c.1761dupC hemizygous mutation in exon 14 of the voltage-dependent calcium channel α1F subunit gene (CACNA1F gene). The results of protein sequence homology analysis showed that the site was highly conserved in multiple species; the results of bioinformatics analysis showed that the CACNA1F gene c.1761dupC (pY588fs) subsequently had a frameshift mutation and became a stop at position 10. Codons appear translational termination in the conserved regions of the protein. According to the standards and guidelines of the American College of Medical Genetics and Genomics, the mutation was judged to be a possible pathogenic variant. The mother of the proband (Ⅰ2) was a carrier of this site mutation. The clinical and genetic test results of the father and elder brother of the proband were not abnormal. ConclusionCACNA1F gene c.1761dupC is the pathogenic mutation site of the Schubert-Bornschein type incomplete CSNB family.
ObjectiveTo explore the light response, retinal inflammation and apoptosis of the retinal ganglion cells (RGCs) 1 year after the new type of channelrhodopsin PsCatCh2.0 was transfected into the retina of rd1 mice. MethodsTwenty-four male rd1 mice were randomly divided into rd1 experimental group and rd1 control group, 12 mice in each group. 1.5 μl of recombinant adeno-associated virus (rAAV)2/2-cytomegalovirus (CMV)-PsCatCh2.0-enhanced green fluorescent protein (EGFP) was injected into the vitreous cavity 1 mm below the corneoscleral limbus of mice in the rd1 experimental group, and the same dose of recombinant virus was injected 2 weeks later at temporal side 1 mm below the corneoscleral limbus. One year after virus injection, the light response of RGCs expressing PsCatCh2.0 was recorded by patch clamp technique; the expression of PsCatCh2.0 in the retina was evaluated by immunofluorescence staining; the transfection efficiency of recombinant virus was evaluated by the transfection efficiency of virus and the number of RGCs. Hematoxylin-eosin staining was performed to measure the inner retinal thickness. Western blotting was used to detect the protein expression of nuclear factor (NF)-κB p65 in retina; real-time quantitative polymerase chain reaction was used to detect the relative expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and Bax mRNA. Terminal deoxynucleotidyl transferase kit was used to observe the apoptosis of retinal cells in each group of mice. ResultsOne year after the intravitreal injection of recombinant virus, PsCatCh2.0-expressing RGCs can still generate 30 pA photocurrent. The virus PsCatCh2.0-EGFP was mainly transfected into RGCs, and partly transfected into amacrine cells, almost no transfection was seen in bipolar and horizontal cells. There were no significant differences in the number of RGCs and thickness of the inner retina between the rd1 experimental group and the rd1 control group (F=14.35, 0.05; P＞0.05), while the rd1 experimental group NF-κB p65 protein expression, TNF-α and IL-6 mRNA quantification were significantly lower than those of rd1 control group (F=4.61, 5.91, 5.78; P＜0.05). The number of red fluorescent apoptotic cells in the retina of mice in the rd1 experimental group was less than that in the rd1 control group, and the Bax mRNA expression was lower than that in the rd1 control group, and the difference was statistically significant (F=7.52, P＜0.01). ConclusionOne year after intravitreal injection of recombinant virus, the PsCatCh2.0 expressing RGCs can still generate photocurrent. Long term transfection and expression of PsCatCh2.0 has no obvious cytotoxic effect on RGCs, nor it increases the inflammatory effect of the retina of rd1 mice with retinal degeneration.
Inherited eye disease is a heterogeneous group of eye disorders caused by genetic defects, which has many genetic characteristics, such as multiple inheritance modes and numerous gene variation types. Over the past few decades, genetic testing has improved significantly, with more and more known disease-causing gene variants identified. With the rapid development of high-throughput sequencing technology, clinical diagnosis and treatment of eye genetic diseases have been accelerated, and molecular diagnosis of eye genetic diseases has become an important step in accurate diagnosis and treatment. How to correctly select and evaluate each kind of genetic testing technology, reasonably standardize the use of genetic testing technology, and provide patients with more accurate genetic counseling are problem that clinicians need to seriously consider.
Inherited retinal diseases (IRD) are a group of genetic disorders with high genetic and clinical heterogeneity. Patients with IRD may have their clinical diagnosis confirmed by genetic testing. Over the past 30 years, rapid advances in molecular genetics have raised the disease-causing gene variant detection rate and the accuracy of genetic testing, which provide hope to patients. The genetic diagnosis of patients with IRD is complicated due to the overlapping clinical phenotypes, and the fact that different variants lead to different phenotypes and severity even of the same gene. It is very important to overall evaluate the clinical phenotype of patients, precisely select genetic testing methods, and reasonably define disease-causing genes and variants during genetic diagnosis, which can guide the patient's subsequent treatment and provide genetic counseling.
Purpose To investigate the blood dynamic feature of choroid in normal eyes. Methods Indocyanine green angiography (ICGA) was performed in each of fifty consecutive normal eyes. Results The earliest fundus fluorescence emerged at the mean timiest fundus fluorescence emerged at the mean time of (14.25plusmn;3.59) seconds,it represented the beginning of filling of choroidal arteries located at the posterior pole.The irrigation of choroidal veins appeared at the mean time of (15.03plusmn;3.44) seconds.At the time threre was the overlapping imaging appearance of choroisal arteries and veins.The most hyperfluorescent areas appered at the mean time of(16.75plusmn;3.78) seconds with definite shapes located at the posterior pole,and this stood for the fluorescence stage of choroidal arteries,veins and capillaries.The fluorescence of choroidal vein began to weaken at 11prime;58Prime;15plusmn;2prime;39Prime;86,and revealed the imaging of late stage of choroidal veins.The latest stage of ICGA was at 22prime;13Prime;22plusmn;3prime;30Prime;55,and presented obscure fluorescence. Conclusion The measurement results and fluorescent features of ICGA of normal eyes can offer consulted bases for the clinical diagnosis of the choroidal diseases. (Chin J Ocul Fundus Dis,1998,14:68-71)
Objective To investigate the clinical characteristic of ocular fundus complications in systemic lupus erythematosus (SLE). Methods In 25 cases of SLE with the ocular fundus complications, the ocular fundus, the other ocular tissues, general lesions，and antinuclear antibody (ANA ), anti-double-stranded DNA（anti-dsDNA）, complement 3 (C3), complement 4 (C4)and erythrocyte sedimentation rate(ESR) were analyzed retrospectively. Results In the 25 cases, “classic” SLE retinopathy in 15 (25 eyes), retinal vein occlusion (RVO) in 9 (12 eyes), RVO combined with retinal arter y occlusion in 1 (2 eyes), exudative retinal detachment in 1 (2 eyes), vitreous hemorrhage combined with neovascular glaucoma in 1 (1 eye), and optic discedem a except RVO in 3 (6 eyes) were found. Nine cases accompanied with other ocular signs and 21 with general lesions. Positive ANA and anti-dsDNA and elevated ESR in all of the patients, decreasing C3 in 19, and C4in 17 were found.Conclusions SLE can cause serious ocular fundus complications accompanied with other ocular signs. Regular ophthalmic examination should be performed on the patients with SLE to detect and treat the ocular complications promptly. (Chin J Ocul Fundus Dis，2004，20：206-208)