Objective To investigate the cilinical value of indocyanine green angiography(ICGA) in patients with Vogt-Koyanagi-Harada syndrome(VKH). Methods Fundus fluorescein angiography(FFA) and indocyanine green angiography(ICGA) were used for comparative analyses in 26 cases(52 eyes)of VKH. Results In the acute stage of VKH,FFA revealed the multifocal leakage in the pigment epithelium and the multifocal serous retinal detachment,and the typical FFA manifestations disappeard following treatment．In the acute stage of the disease the ICGA showed:(1)numerous patchy areas of hypofluorescence and decreased flurescence in large and middle choroidal vessels(66.7%);(2)dilatation of the choroidal vessels(70.8%)and(3)in latephase of ICGA,the patchy areas of hyperfluorescence(79.2%).During the recovery stage of the disease,the abnormal undings in ICGA were resolved slower than those found in FFA. Conclusions ICGA may assist in providing valuable informations on choroidal circulation of VKH and be useful in evaluating the curative effects． (Chin J Ocul Fundus Dis,20000,16:9-11)
Objective To observe the characteristics of fundus autofluorescence (AF) in short wavelength AF (SW-AF) and Near Infrared AF (NIR-AF), and their relationship with visual fields. Methods Twelve patients (24 eyes) with primary RP were enrolled in this study. The patients included nine males (18 eyes) and three females (six eyes). The patients aged from 15 to 69 years, with a mean age of (35.33plusmn;15.03) years. All the patients were examined for color photography, SW-AF, NIR-AF, visual fields and optical coherence tomography examination. Results There were hyper-AF ring of varying sizes in posterior pole by SW-AF and NIR-AF examinations. The area of hypo-AF which located in SW-AF hyper-AF ring had a positive correlation with the area of hyper-AF in the NIR-AF (r=0.662，P＜0.05). OCT showed that outside the hyper-AF ring, there were disconnected inner segment/outer segment (IS/OS) junction and external limiting membrane, and thinned outer nuclear layer and retinal pigment epithelium. Peripheral retinal osteocytes-like pigmentation showed non fluorescence in SW-AF and NIR-AF. The plaque-like area showed mottled and low fluorescence examined by SW-AF. SW-AF hyper-AF ring had a positive correlation with visual fields (r=0.492，P＜0.05). Conclusions The area of hypo-AF inside of the SW-AF hyper-AF ring is related to visual fields in RP patients. The retinal structures in the hypo-AF area inside of the SW-AF hyper-AF ring, and in the NIR-AF hyper-AF region are normal.
Objective To observe the expression of cyclin dependent kinase 5 (Cdk5) and p25 in the pathogenesis of retinitis pigmentosa (RP) in Royal College of Surgeon (RCS) rats and its relationships with apoptosis. To explore the mechanism of Cdk5 and p25 induced photoreceptor apoptosis in the pathogenesis of RP. Methods Retinas of RCS and RCS-rdy+ rats were obtained at the ages of postnatal day 17, 25, 35, 60. The retinal structure and thickness of outer nuclear layer were measured by optical microscopy. The expression of Cdk5, p25, cleave-caspase 3 in the retina was evaluated by immunohistochemistry. The protein expression of cleave-caspase 3 in the retina was determined by Western blot. The apoptosis of retinal cells was examined by terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL). The mean absorbance value of apoptotic cells was analyzed by SPSS 17.0 software. Results The retinal thickness of the RCS rats was significantly reduced in comparison to the RCS-rdy+ rats as the postnatal days progressed, particularly in the layer of rods and cones and the outer nuclear layer. The expression level of Cdk5, p25, cleave-caspase 3 of RCS rats increased from postnatal 17 days to postnatal 35 days, while decreased on postnatal 60 days; but there was no obvious change of above indexes in RCS-rdy+ rats. The protein expression of cleave-caspase 3 in the RCS rats was significantly increased with progression of postnatal days to postnatal 35; but there was no obvious similar change in RCS-rdy+ rats. The results of TUNEL showed that the apoptotic cells significantly increased in the outer nuclear layer of RCS rats from postnatal 17 days to postnatal 35 days, while decreased on postnatal 60 days; but there was no obvious change of above index in RCS-rdy+ rats. This study showed that there were significant correlations between the following variables: Cdk5 expression and p25 expression, Cdk5 expression and cleave-caspase 3 expression, Cdk5 expression and apoptotic cells, p25 expression and cleave-caspase 3 expression, p25 expression and apoptotic cells, cleave-caspase 3 expression and apoptotic cells. The partial correlation coefficients were 0.949, 0.808, 0.959, 0.887, 0.979, 0.852, respectively and the P value was 0.000. Conclusions The apoptotic cells significantly increases and the expression level of Cdk5, p25, cleave-caspase 3 of RCS rats increases from postnatal 17 days to postnatal 35 days. The tendency of apoptotic cells to increase is consistent with the change of Cdk5, p25, cleave-caspase 3 expression. The apoptosis of photoreceptor cells is related to increasing expression of Cdk5 and p25 in RCS rats. Cdk5 may be involved in the development of RP in RCS rats.
ObjectiveTo observe the clinical characteristics of primary retinitis pigmentosa (RP) complicated with glaucoma.MethodsA retrospective clinical study. From June 2008 to March 2020, the diagnosis of primary RP were included in the diagnosis confirmed by the eye examination of West China Hospital of Sichuan University included 4794 eyes of 2432 patients. Among them, 4679 eyes (97.2%, 2364/2432) were in 2364 cases with RP alone, and 115 eyes were in 68 cases with RP combined with glaucoma (2.80%, 68/2432). All affected eyes underwent best corrected visual acuity (BCVA) and intraocular pressure examination. The BCVA examination was carried out using the international standard visual acuity chart, which was converted into the logarithmic minimum angle of resolution (logMAR) visual acuity during statistics. The 67 eyes of 40 patients with RP and glaucoma with complete follow-up data were analyzed to observe the proportion of different glaucoma types, logMAR BCVA, intraocular pressure and other clinical characteristics, as well as treatment methods and post-treatment intraocular pressure control. After treatment, the intraocular pressure ≤21 mm Hg (1 mm Hg=0.133 kPa) was regarded as intraocular pressure (IOP) control; ＞21 mm Hg was regarded as uncontrolled IOP.ResultsAmong the 67 eyes of 40 cases with complete follow-up data, 5 cases (7 eyes) with primary open-angle glaucoma (10.45%, 7/67), 56 cases (58 eyes) with angle-closure glaucoma (ACG) (86.57%, 58/67), 4 cases (4 eyes) with neovascular glaucoma (5.97%, 4/67), 2 of them had both ACG and neovascular glaucoma. Among 58 ACG eyes, 17 eyes were acute ACG (25.37%, 17/67), 21 eyes were chronic ACG (31.34%, 21/67), and 2 eyes were suspicious angle closure (2.99%, 2/67), lens dislocation secondary to angle-closure glaucoma in 8 eyes (11.94%, 8/67), chronic angle-closure glaucoma after anti-glaucoma surgery, intraocular lens shift in 5 eyes (7.46%, 5/67), 5 eyes (7.46%, 5/67) secondary to glaucoma with true small eyeballs. The logMAR BCVA 3.50 of the affected eye,＜3.50-＞2.00, ≤2.00-≥1.30,＜1.30-＞1.00, ≤1.00-0.52,＜0.52 were 9 (13.43%, 9/67), 30 (44.78%, 30/ 67), 7 (10.45%, 7/67), 4 (5.97%, 4/67), 11 (16.42%, 11/67), 6 (8.96%, 6/67) eyes, which correspond to mean intraocular pressure were 32.31±11.67, 30.15±14.85, 28.17±13.19, 31.50±17.25, 18.71±8.85, 14.12±4.25 mm Hg. Among 67 eyes, 37eyes (55.22%, 37/67), 18eyes (26.86%, 18/67), and 6 (8.96%, 6/67) eyes underwent surgery, medication alone, and peripheral iris laser perforation treatment, respectively. The treatment of 6 eyes was abandoned (8.96%, 6/67). Malignant glaucoma occurred in 3 eyes (8.11%, 3/37) after the operation, all of which were after trabeculectomy of the ACG eye. After treatment, intraocular pressure was controlled in 37 eyes (55.22%, 37/67), 19 eyes were not controlled (28.36%, 19/67), and 11 eyes were lost to follow-up (16.42%, 11/67).ConclusionsThe incidence of glaucoma in patients with primary RP is 2.80%. ACG is more common, and the combined lens dislocation or intraocular lens shift is more common.
Objective To observe the mutifocal electroretinogram (mfERG) characteristics of rod and cone cells in patients with retinitis pigmentosa (RP) and to evaluate the function of photosensory cell.Methods The mfERG recording technique for rod cell in eight normal subjects (eight eyes) were established and the influence of different brightness lightstimulus in P1 wave amplitude were analyzed. The cone and rod cells mfERG of 38 eyes in 19 patients were recorded and then calculated positive ratio from local signalnoise ratio. The average visual acuity and P1 wave amplitude density of cone mfERG in different types were compared and statistically analyzed. Meanwhile, the changes in P1 wave amplitude of cone and rod mfERG in four quadrants also compared and analyzed. Results Rod cell mfERG in normal subjects can be recorded stably by using blue flashes with low light intensity as 0.04 cd/m2. In patients with RP, the cone and rod cells mfERG can be detectd 65.79% and 10.51% respectively. P1 wave amplitude density in type I of cone cell mfERG was significantly higher than that in type II (t=5.21,P=0.000). There were no differences in average visual acuity (t=1.15, P=0.612). P1 wave amplitude density in type I was negatively related to logMAR visual acuity （r=-0.48，P=0.04）.The comparison of rod and cone cells mfERG in local wave characteristics showed that P1 wave amplitude densities had spatial relationship in each area. Conclusions The results suggested highly variable central responses in cone cell in RP patients, higher positive recorded ratio in cone cell than rod cell and spatial correspondence between the function of reserved cone and rod cells.
Cilia are hair-like protuberance on cells of the human body that play a vital role in organs generation and maintenance. Abnormalities of ciliary structure and function affect almost every system of the body, such as the brain, eyes, liver, kidney, bone, reproductive system and so on. Retinal photoreceptor cells are one of sensory neurons which convert light stimuli into neurological responses. This process, called phototransduction, takes place in the outer segments (OS) of rod and cone photoreceptors. OS are specialized sensory cilia, and disruptions in cilia genes, which are causative in a growing number of non-syndromic retinal dystrophies, such as retinitis pigmentosa, Leber’s congenital amaurosis. These syndromes are genetically heterogeneous, involving mutations in a large number of genes. They show considerable clinical and genetic overlap. At present, there are few researches on retinal ciliopathies and clinical treatment strategy. This review shows a comprehensive overview of ciliary dysfunction and visual development related diseases, which contributes to understand the characteristics of these diseases and take early intervention in clinic.
Retinitis pigmentosa (RP) is a group of hereditary blinding fundus diseases caused by abnormalities in photoreceptors of the retina. RP is highly heterogeneous in hereditary and cdinical phenotypes. It can be divided into simple type RP and syndrome type RP. The main inheritance patterns are autosomal dominant, autosomal recessive inheritance and X-linked inheritance. With the popularization and clinical application of gene sequencing technology, more and more disease-causing genes have been discovered, and these genes are mainly expressed in photoreceptor cells and retinal pigment epithelial cell. ln-depth understanding of RP pathogenic genes not only provides a theoretical basis for RP diagnosis and genetic counseling, but also provides guidance for RP gene therapy.
ObjectiveTo observe the gene mutations and clinical phenotypes in patients with Usher syndrome type 2 (USH2) and retinitis pigmentosa (RP).Methods From August 2018 to January 2019, 4 patients and 11 normal family members from 3 families of USH2 and RP who visited Henan Eye Hospital were enrolled in the study. Detailed medical history was obtained and visual acuity, fundus color photography, OCT, visual field, full field ERG examination were performed. Among the three families, pedigree 1 was diagnosed with USH2, pedigree 2 and pedigree 3 were diagnosed with RP. The peripheral venous blood of patients and their family members were collected, and the whole genomic DNA was extracted. Targeted capture next generation sequencing analysis was performed on these members, and Sanger sequencing and family co-segregation were verified.ResultsIn the family F1, the proband had symptoms of RP and sensorineural deafness. Sequencing revealed two heterozygous frameshift variants: c.13877-13880 del AGAC (p. Q4626P) in exon 64 and c.798 del T (p. F266L) in exon 5 of USH2A. Both patients of family 2 and 3 showed RP signs without deafness. Two heterozygous variants c.15178T＞C (p. S5060 P) in exon 70 and c.6986C＞A (p. P2329H) in exon 37, and a pathogenic heterozygous variant c.5836C＞T (p. R1946X) in exon 29 of USH2A were identified in family F2. A heterozygous missense variant c.14951C＞T (p. P4984L) in exon 68 and a variant c.11156G＞A (p. R3719H) in exon 57 of USH2A were found in family F3. The results of conservation analysis showed that the corresponding amino acid sites of USH2A p.Q4626P, p.F266L, p.S5060P, p.P2329H and p.P4984L were highly conserved in many species. Among these 7 pathogenic variants detected, M1-M4 and M6 were novel.ConclusionsMutation USH2A gene are the main cause of USH2 and non-syndromic RP. Different variants affect protein translation and synthesis, consequently causing different clinical phenotypes.
ObjectiveTo investigate the current status of research in gene therapy for retinitis pigmentosa (RP) from 2005 to 2024. MethodsThe literature related to gene therapy for RP included in the Web of Science Core Collection dataset from January 1, 2005 to September 15, 2024 was retrieved and screened. The bibliometrix package of R software was used to analyze the annual trend of the number of publications, citation frequency, distribution of countries/regions of the literature, and distribution of journals containing the articles. CiteSpace software was used to perform keyword clustering analysis and the keywords bursts analysis. ResultsA total of 209 articles were included. There was an overall fluctuating upward trend of annual publications from 2005 to 2024, with the highest number of publications in 2023 at 26 (12.4%, 26/209), and the lowest number of publications in 2006 at 2 (0.9%, 2/209). There was an overall increasing trend in the frequency of citations to relevant literature. Corresponding authors from the United States had the highest total number of publications with 98 (46.9%, 98/209). Among authors, Hauswirth from the University of Florida, USA, had the most with 25 (12.0%, 25/209). Among institutions, Columbia University, USA, had the most with 55 (26.3%, 55/209). Among journals, Mol Ther had the most with 25 (12.0%, 25/209), and it had the highest 2023 impact factor of 12.1. Keyword clustering analysis yielded eight valid clusters, namely #0 P23H, #1 AAV, #2 PDE6B, #3 CRB1, #4 RPGR, #5 antisense oligonucleotide, #6 NR2E3, and #7 NRL, which intersected with each other with good continuity. The keywords bursts analysis showed that the keyword with the longest emergence time was RNAi, followed by PDE and PDE6. USH2A, CRB1, CRISPR Cas9, base editing, and ORF15 were keywords that emerged in recent years and were continuously studied. ConclusionsRP gene therapy research literature has shown an increasing trend from 2005 to 2024, with the highest number of publications from research organizations and scholars in the United States. Currently, studies focus on RHO, PDE6B, CRB1, RPGR, NR2E3, and NRL gene. In recent years, there has been a gradual increase in studies on USH2A, CRB1 genes, and the RPGR ORF15 region. CRISPR Cas9 and base editing gene therapy strategies are being developed.
Objective To detect characteristics and the pathogenesis of rhodopsin (RHO) gene mutation in an inbreeding family with autosomal recessive retinitis pigmentosa (ARRP). Methods Peripheral venous blood 5-8 ml was abstracted from 8 members in the inbreeding ARRP family and 10 control individuals. DNA gene group was picked. Extron 1-5 of RHO gene was amplified by polymerase chain reaction (PCR)，and the mutation of RHO gene was screened by direct DNA sequence measurement. Results The Gln-344-Arg mutation in the RHO gene was detected in 3 patients with ARRP and homozygotes of the mutation in 3 patients were found. Heterozygous of the mutation was detected in the parent of patients and 1 healthy family member. No mutation of RHO gene was found in 2 healthy family members and 10 control individuals. Conclusions The Gln-344-Arg mutation in the RHO gene may be the pathogenic factor of the ARRP family; the frequency of the mutation of RHO gene may increase in the in breeding ARRP family.(Chin J Ocul Fundus Dis，2004，20：145-148)