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 investigate whether mutations exist in codon 58 and codon 347 of the rhodopsin gene in patients with autosomal dominant retinitis pigmentosa(ADRP)． Methods Point mutations at codons 58 and 347 were detected by restriction endonuclease digestion of exons 1 and 5 amplified by polymerase chain reaction(PCR)．This method was applied to screen genomic DNAs from 57 patients of 38 families with ADRP and 60 normal controls． Results Four patients from one family of ADRP were confirmed to have a point mutation at the second nucleotide of codon 58,and 6 patients from two families of ADRP were found to have a mutation at codon 347．None of these mutations were found in 60 normal subjects． Conclusion It is suggested that molecular genetic heterogeneity exists within ADRP and some subtypes of ADRP are caused by points mutations of the rhodopsin gene． (Chin J Ocul Fundus Dis,1998,14:108-110)
Objective To detect and analyse the mutations in rhodopsin gene of members in a family affected by autosomal dominant retinitis pigmentosa (ADRP). Methods Using the polymerase chain reaction (PCR), we amplified exon 1-5 of rhodopsin gene in patients with ADRP,and analyzed it with direct sequence measuement. Results The Gly-182-Asp mutation in the rhodopsin gene was detected in most of affected members of this ADRP family, but no mutation was detected in two affected members and the control ones. Conclusion We cannot regard the Gly-182-Asp mutation in the rhodopsin gene as the pathagenic factor of the ADRP family. It is likely there is a new gene next to the rhodopsin gene. (Chin J Ocul Fundus Dis, 2002, 18: 256-258)
Objective To observe the interferon-gamma; (IFN-gamma;), interleukin-2 (IL-2) levels of Th1 cytokine and IL-4、IL-10 levels of Th2 cytokine in serum and culture supernatants of splenic cells of the rats in the prevention of experimental autoimmune uveoretinitis（EAU）by oral tolerance. Methods 72 Lewis rats were randomly divided into EAU group，oral tolerance group (which including 10 mu;g、100 mu;g、1 mg、10 mg of S antigen group respectively) and control group，12 rats in each group. The animal model of EAU was induced by immunization with S antigen（50 mu;g）and Freundrsquo;s complete adjuvant. Oral tolerance 10 mu;g、100 mu;g、1 mg and 10 mg group were fed with 1 ml mixture of 10 mu;g、100 mu;g、1 mg、10 mg S antigen and 1 mg trypsin inhibitor respectively by intubation，once the other day，totally 7 times，and then induced EAU according to above methods；control group was fed with 1 ml mixture of phosphate buffered saline and 1 mg trypsin inhibitor，once the other day，totally 7 times，and then induced EAU. The clinical manifestation of EAU in the eye were recorded,the eyeballs were enucleated at the peak of EAU，followed by pathological grading. Meanwhile the serum was colleced; splentic cells were separated and cultured to collect the supernatant. Cytokine levels of IFN-gamma;, IL-2, IL-4 and IL-10 in serum, cultured supernatant of splenic cells were determined by enzyme-linked immunosorbent assay (ELISA). Results Compared with EAU and control group, the levels of IFN-gamma; and IL-2 (Th1 cytokine) in the serum in 100 mu;g and 1 mg group were decreased while the levels of IL4 and IL10 (Th2 cytokine) were increased，the differences were statistically significant（F=51.9, 68.8, 35.7,7.5,P＜0.01). Compared the levels of Th1 and Th2 cytokines in the serum in 10 mu;g, 10 mg group with EAU and control group, the differences were not statistically significant. In 100 mu;g、1 mg group, the levels of IFN-gamma; and IL-2 (Th1 cytokine) in the culture supernatant of splenic cells were decreased while the levels of IL-4 and IL-10 (Th2 cytokine) were increased, compared with EAU and control group, the differences were statistically significant（F=57.1,15.6,33.1,167.7, P＜0.01）. Compared the levels of Th1 and Th2 cytokine in the culture supernatant of splenic cells in 10 mu;g、10 mg groups with EAU and control group, the difference are not statistically significant. Conclusions In the process to prevent EAU by oral intake, the levels of IFN-gamma; and IL-2 (Th1 cytokine ) were decrease while the levels of IL-4 and IL-10 (Th2 cytokine). Oral administration with too high or low dose of the antigen can not prevent EAU as well as the cytokine levels do not change obviously. Cytokines has played an important role in the prevention of EAU.
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)
Retinitis pigmentosa (RP) is an inherited retinal disease characterized by degeneration of retinal pigment epithelial cells. Precision medicine is a new medical model that applies modern genetic technology, combining living environment, clinical data of patients, molecular imaging technology and bio-information technology to achieve accurate diagnosis and treatment, and establish personalized disease prevention and treatment model. At present, precise diagnosis of RP is mainly based on next-generation sequencing technology and preimplantation genetic diagnosis, while precise therapy is mainly reflected in gene therapy, stem cell transplantation and gene-stem cell therapy. Although the current research on precision medicine for RP has achieved remarkable results, there are still many problems in the application process that is needed close attention. For instance, the current gene therapy cannot completely treat dominant or advanced genetic diseases, the safety of gene editing technology has not been solved, the cells after stem cell transplantation cannot be effectively integrated with the host, gene sequencing has not been fully popularized, and the big data information platform is imperfect. It is believed that with the in-depth research of gene sequencing technology, regenerative medicine and the successful development of clinical trials, the precision medicine for RP will be gradually improved and is expected to be applied to improve the vision of patients with RP in the future.
Objective To evaluate the therapeutic effects of vitrectomy on chronic and refractory Behcet′s diseases. Methods The clinical data of 8 patients (10 eyes) with Behcet′s diseases from 0.5 to 3 years after vitrectomy were retrospectively analyzed. Pre-and post-operative visual acuity, control of inflammation after the surgery, and the recurrence were observed and analyzed. Both of the eyes were involved in all of the patients, including complete Behcet′s diseases in 5 and incomplete in 3. Results Vitreous opacity and liquefaction were found in all of the involved eyes, dark retina and thin retinal vessels were seen in most of the eyes, and vascular obstruction or sheath-like changes in different degrees were detected in some eyes. Improvement of visual acuity was observed in all of the eyes which had undergone the treatment after the operation. There was significant difference between the visual acuity before the surgery and at the 1st and 2nd week and the 1st and 6th month after the surgery. During the follow-up period, recurrence of the inflammation was found in 3 eyes within 1 month and in 6 eyes within 6 months; no recurrence was found in 4 eyes after the operation. No acute recurrence of inflammation was found after operation in the involved eyes. Conclusion Vitrectomy for chronic and refractory Behcet′s diseases may improve the visual acuity of the involved eyes, and the surgery is safe and effective. (Chin J Ocul Fundus Dis, 2005, 21: 357-359)
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 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 analyze the subfoveal choroidal thickness in retinitis pigmentosa (RP) patients and to evaluate the correlation between the subfoveal choroidal thickness (SCT) and visual function. MethodsTotally 42 RP patients (84 eyes) and 49 age and diopter-matched normal controls (98 eyes) were enrolled in this study. All the patients were taken the enhanced depth imaging technique of optical coherence tomography (EDI-OCT) examination for the measurement of the SCT. The covariate analysis was used to analyze the interaction effect between age and group. Then the SCT was amended. The RP patients were examined by 30°visual field test (T32 or LVC program) and electroretinogram (ERG) test. 32 eyes examined by T32 program, 52 eyes examined by LVC program. The waveform of ERG, mean sensitivity (MS) and mean defect (MD) were recorded. The relationship of SCT, MS and MD were analyzed by Pearson correlation analysis. ResultsThe SCT of RP patients and controls were (223.12±69.59), (288.29±52.36) μm. The covariate analysis of covariance with different age group interaction was not statistically significant (F=1.619, P=0.205), as amended SCT of RP patients and controls were (217.34±6.60), (293.20±6.00) μm, respectively. The SCT was decreased in RP patients (t=7.042, P < 0.001). Among 84 eyes, bright cone response weaken in 35 eyes, scotopic rod response weaken in 31 eyes. The difference of SCT in different ERG waveform was not significant (t=-0.976, -1.584; P=0.332, 0.117). The MS and MD of 32 eyes using T32 program were (9.05±6.42), (18.84±6.30) dB, the SCT was (209.83±71.48) μm; the MS and SCT of 52 eyes using LVC program were (7.14±5.03) dB and (228.32±66.32) μm. The SCT was related to MS (r=0.494, P=0.003) and MD (r=-0.448, P=0.009) in eyes using T32 program. There was no correlation between SCT and MD in eyes using LVC program (r=-0.232, P=0.095). ConclusionsThe SCT of RP patients is thinner than that of normal controls. The SCT of RP patients is related to MS and MD of T32 program, but not correlated to ERG waveform and MS of LVC program.