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 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.
Retinitis pigmentosa (RP) is a genetic disorder of photoreceptor cell apoptosis and retinal pigment epithelium (RPE) cell atrophy caused by gene mutation. The clinical manifestations are night blindness, peripheral visual field loss and progressive vision loss. RPE cell apoptosis plays an important role in the progression of RP, and exogenous implantation of RPE cells as an alternative therapy has shown certain efficacy in animal experiments and clinical trials. With the diversification of cell sources, the update of surgical techniques and the continuous emergence of biological materials, more possibilities and hopes are provided for cell therapy. To further promote the development of this field in the future, it is still necessary to strengthen the cooperation between medicine, bioengineering and other disciplines in the future to jointly promote the innovation and development of therapeutic methods. It is believed that RPE cell transplantation therapy will show a brighter prospect in the future
Objective To observe the effect of Minocycline on RP process of retinal pigmentary degeneration rd mice［C3H/HeN (Pde6brd-/rd-)］. Methods 40 rd mice were divided into ten groups randomly: 5 experimental groups and 5 control groups, 4 rd mice in each group. The experimental group received intraperitoneal injection of minocycline 22.5mg/kg while the control group received saline 10ml/kg every day from the postnatal day 1 (P1) . Mice were sacrificed at P1, P7, P14, P21 and P28 respectively. Eyeballs were enucleated to carry out histology observation and apoptosis cell detection. Meanwhile, to statistically analyze the number of retinal photoreceptor cells,the thickness of outer nuclear layer (ONL)and the number of apoptosis cells. Results （1）Photoreceptor cell began to apoptosis on P7, peaked on P14, and totally disappeared on P28. （2）No statistically significant differences were found of the number of photoreceptor cells and the thickness of ONL on P7 between the experimental group and the control group. (3) The number of photoreceptor cells and the thickness of ONL in the experimental were more than that in the control group at P14, P21, P28 respectively, the differences are statistically significant（Plt;0.05）. (4) The apoptotic cells on ONL were less in the experimental group than that in the control group on P7 and P14 respectively, the difference are statistically significant（Plt;0.05）. Conclusions Minocycline appears to protect photoreceptor cell from apoptosis in the early stage of the retinal degeneration mice, but it may not completely prevent RP from occurrence.
Objective To observe the gene mutation and clinical phenotype of patients with retinitis pigmentosa (RP) and cone rod dystrophy (CORD). Methods Thirty-seven patients with RP and 6 patients with CORD and 95 family members were enrolled in the study. The patient’s medical history and family history were collected. All the patients and family members received complete ophthalmic examinations to determine the phenotype, including best corrected visual acuity, slit lamp microscope, indirect ophthalmoscopy, color fundus photography, optical coherence tomography, full-field electroretinogram, and fluorescein fundus angiography. DNA was abstracted from patients and family members. Using target region capture sequencing combined with next-generation sequencing to screen the 232 candidate pathogenic mutations. Polymerase chain reaction and direct sequencing were used to confirm the pathogenic pathogenic mutations and Co-segregation is performed among members in the family to determine pathogenic mutation sites. The relationship between genotype and clinical phenotype of RP and CORD was analyzed. Results Of the 37 patients with RP, 13 were from 6 families, including 4 families with autosomal dominant inheritance, 2 families with autosomal recessive inheritance, and 3 in 6 families were detected pathogenic gene mutations. 24 cases were scattered RP. Six patients with CORD were from four families, all of which were autosomal recessive. Of the 43 patients, 21 patients were detected the pathogenic gene mutation, and the positive rate was 48.8%. Among them, 15 patients with RP were detected 10 pathogenic gene mutations including USH2A, RP1, MYO7A, C8orf37, RPGR, SNRNP200, CRX, PRPF31, C2orf71, IMPDH1, and the clinical phenotype included 10 typical RP, 2 cases of RPSP, 3 cases of Usher syndrome type 2 and 6 cases of CORD patients were all detected pathogenic gene mutations, including 2 cases of ABCA4, 2 mutations of RIMS1 gene, 1 case of CLN3 gene mutation, and 1 case of CRB1 and RPGR double gene mutation. Conclusions RP and CORD are clinically diverse in genotype and clinically phenotypically similar. For patients with early RP and CORD, clinical phenotype combined with genetic analysis is required to determine the diagnosis of RP and CORD.