Myopia with X-linked retinitis pigmentosa results from a novel gross deletion of RPGR gene

AIM: To identify mutations with whole exome sequencing(WES) in a Chinese X-linked retinitis pigmentosa(XLRP) family. METHODS: Patients received the comprehensive ophthalmic evaluation. Genomic DNA was extracted from peripheral blood and subjected to Sure Select Human All Exon 6+ UTR exon capture kit. The exons were sequenced as 100 base paired reads on Illumina HiS eq2500 system. Only mutations that resulted in a change in amino acid sequence were selected. A pattern of inheritance of the RP family was aligned to identified causal mutation.RESULTS: We analysed the data of WES information from XLRP family. The analysis revealed a hemizygous large genomic deletion of RPGR c.29113 del was responsible for this XLRP. The gross deletion lead to a frame-shift mutation and generate stop codon at 7 animo acid behind Asp(D10 Afs*7), which would serious truncate RPGR protein. The novel frame-shift mutation was found to segregate with retinitis pigmentosa(RP) phenotype in this family. Bilateral myopia was present on the male patients, but carrier female showed unilateral myopia without RP.CONCLUSION: Our study identifies a novel frame-shift mutation of RPGR in a Chinese family, which would expand the spectrum of RPGR mutations. The geno-phenotypic analysis reveals a correlation between RP and myopia. Although exact mechanism of RP related myopia is still unknown, but the novel frame-shift mutation will give our hit on studying the molecular pathogenesis of RP and myopia.

Identification of a novel p.R1443W mutation in RP1 gene associated with retinitis pigmentosa sine pigmento

AIM:To screen mutations in the retinitis pigmentosa 1(RP1) gene and the rhodopsin(RHO) gene in Chinese patients with retinitis pigmentosa sine pigmento(RPSP)and describe the genotype-phenotype relationship of the mutations.·METHODS:Twenty affected,unrelated Chinese individuals with RPSP(4 autosomal dominant RPSP,12autosomal recessive RPSP and 4 unknown inheritance pattern) were recruited between 2009 and 2012.The clinical features were determined by complete ophthalmologic examinations.Polymerase chain reaction(PCR) and direct DNA sequencing were used to screen the entire coding region and splice junctions of the RP1gene and the RHO gene.The cosegregation analysis and population frequency studies were performed for patients with identified mutations.·RESULTS:Five variants in the RP1 gene and one in the RHO gene were detected in 20 probands.Four missense changes(rs444772,rs446227,rs414352,rs441800) and one non-coding variant(rs56340615) were common SNPs and none of them showed a significant relationship with RPSP.A missense mutation p.R1443W was identified in the RP1 gene in three affected individuals from a family with autosomal dominant RPSP and was found to cosegregate with the phenotype in this family,suggestive of pathogenic.In addition,population frequency analysis showed the p.R1443W mutation was absent in 300 healthy controls.·CONCLUSION:The identification of p.R1443W mutationcosegregating in a family with autosomal dominant RPSP highlights an atypical phenotype of the RP1 gene mutation,while RHO gene is not associated with the pathogenesis of RPSP in this study.To our knowledge,this is the fist mutation identified to associate with RPSP.

A novel mutation of RPGR in a Chinese family with X-linked retinitis pigmentosa

·AIM:To identify potential mutations and elucidate the clinical findings of male patients and female carriers of X-Iinked retinitis pigmentosa(XLRP)in a Chinese family.·METHODS:A four generation pedigree was collected that consisted of 20 individuals.Genomic DNA was extracted from peripheral blood,and then the target fragments were amplified by PCR and sequenced directly.In addition,all affected patients and female carriers underwent comprehensively ophthalmic evaluation.·RESULTS:A novel mutation c.2865 G>A p.W955 X in RPGR gene was identified of this family,including four affected individuals and eight carriers.All male patients,aging from 7 to 31 y,tended to have more various,even potentially deleterious clinical features of RP.At the same time,individuals with heterozygous mutations(carriers)manifested a wide spectrum of clinical features.Herein,only two male patients and three female carriers manifested pathological myopia(PM).Among the female carriers,half of subjects who harbor poor visual acuity suffered esotropia or exotropia.Additionally,16.7%and 66.7%of carriers had abnormal electroretinogram(ERG)and fundus,respectively.·CONCLUSION:In this study,a novel mutation of the RPGR gene is identified,which broadens the spectrum of RPGR mutations,and elaborates the relationship between genotype and phenotype.

A novel pathogenic splicing mutation of RPGR in a Chinese family with X-linked retinitis pigmentosa verified by minigene splicing assay

AIM:To report a novel splicing mutation in the RPGR gene(encoding retinitis pigmentosa GTPase regulator)in a three-generation Chinese family with X-linked retinitis pigmentosa(XLRP).METHODS:Comprehensive ophthalmic examinations including best corrected visual acuity,fundus photography,vision field,and pattern-visual evoked potential were performed to identify the disease phenotype of a six-yearold boy from the family(proband).Genomic DNA was extracted from peripheral blood of five available members of the pedigree.Whole-exome sequencing(WES),Sanger sequencing,and pSPL3-based exon trapping were used to investigate the aberrant splicing of RPGR.Human Splice Finder v3.1 and NNSPLICE v0.9 were used for in silico prediction of splice site variants.RESULTS:The proband was diagnosed as having retinitis pigmentosa(RP).He had severe symptoms with early onset.A novel splicing mutation,c.619+1G>C in RPGR was identified in the proband by WES and in four family members by Sanger sequencing.Minigene splicing assays verified that c.619+1G>C in RPGR would result in the formation of a damaging alternative transcript in which the last 91 bp of exon 6 were skipped,leading to the subsequent deletion of 623 correct amino acids(c.529_619del p.Val177Glnfs*16).CONCLUSION:We identify a novel splice donor site mutation causing aberrant splicing of RPGR.Our findings add to the catalog of pathological mutations of RPGR and further emphasize the functional importance of RPGR in RP pathogenesis and its complex clinical phenotypes.

AAV2-PDE6B restores retinal structure and function in the retinal degeneration 10 mouse model of retinitis pigmentosa by promoting phototransduction and inhibiting apoptosis

Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.

Optimal transcorneal electrical stimulation parameters for preserving photoreceptors in a mouse model of retinitis pigmentosa

Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors,leading to progressive photoreceptor loss.Previous research supports the beneficial effect of electrical stimulation on photoreceptor survival.This study aims to identify the most effective electrical stimulation parameters and functional advantages of transcorneal electrical stimulation(tcES)in mice affected by inherited retinal degeneration.Additionally,the study seeked to analyze the electric field that reaches the retina in both eyes in mice and post-mortem humans.In this study,we recorded waveforms and voltages directed to the retina during transcorneal electrical stimulation in C57BL/6J mice using an intraocular needle probe with rectangular,sine,and ramp waveforms.To investigate the functional effects of electrical stimulation on photoreceptors,we used human retinal explant cultures and rhodopsin knockout(Rho^(-/-))mice,demonstrating progressive photoreceptor degeneration with age.Human retinal explants isolated from the donors’eyes were then subjected to electrical stimulation and cultured for 48 hours to simulate the neurodegenerative environment in vitro.Photoreceptor density was evaluated by rhodopsin immunolabeling.In vivo Rho^(-/-)mice were subjected to two 5-day series of daily transcorneal electrical stimulation using rectangular and ramp waveforms.Retinal function and visual perception of mice were evaluated by electroretinography and optomotor response(OMR),respectively.Immunolabeling was used to assess the morphological and biochemical changes of the photoreceptor and bipolar cells in mouse retinas.Oscilloscope recordings indicated effective delivery of rectangular,sine,and ramp waveforms to the retina by transcorneal electrical stimulation,of which the ramp waveform required the lowest voltage.Evaluation of the total conductive resistance of the post-mortem human compared to the mouse eyes indicated higher cornea-to-retina resistance in human eyes.The temperature recordings during and after electrical stimulation indicated no significant temperature change in vivo and only a subtle temperature increase in vitro(~0.5-1.5°C).Electrical stimulation increased photoreceptor survival in human retinal explant cultures,particularly at the ramp waveform.Transcorneal electrical stimulation(rectangular+ramp)waveforms significantly improved the survival and function of S and M-cones and enhanced visual acuity based on the optomotor response results.Histology and immunolabeling demonstrated increased photoreceptor survival,improved outer nuclear layer thickness,and increased bipolar cell sprouting in Rho^(-/-)mice.These results indicate that transcorneal electrical stimulation effectively delivers the electrical field to the retina,improves photoreceptor survival in both human and mouse retinas,and increases visual function in Rho^(-/-)mice.Combined rectangular and ramp waveform stimulation can promote photoreceptor survival in a minimally invasive fashion.

Retinitis pigmentosa and stem cell therapy

Retinitis pigmentosa(RP)is a group of genetic disorders characterized by progressive degeneration of photoreceptors and retinal pigment epithelium(RPE)cells.Its main clinical manifestations include night blindness and progressive loss of peripheral vision,making it a prevalent debilitating eye disease that significantly impacts patients’quality of life.RP exhibits significant phenotypic and genetic heterogeneity.For instance,numerous abnormal genes are implicated in RP,resulting in varying clinical presentations,disease progression rates,and pathological characteristics among different patients.Consequently,gene therapy for RP poses challenges due to these complexities.However,stem cells have garnered considerable attention in the field of RPE therapy since both RPE cells and photoreceptors can be derived from stem cells.In recent years,a large number of animal experiments and clinical trials based on stem cell transplantation attempts,especially cord blood mesenchymal stem cell(MSC)transplantation and bone marrow-derived MSC transplantation,have confirmed that stem cell therapy can effectively and safely improve the outer retinal function of the RP-affected eye.However,stem cell therapy also has certain limitations,such as the fact that RP patients may involve multiple types of retinal cytopathia,which brings great challenges to stem cell transplantation therapy,and further research is needed to solve various problems faced by this approach in the clinic.Through comprehensive analysis of the etiology and histopathological changes associated with RP,this study substantiates the efficacy and safety of stem cell therapy based on rigorous animal experimentation and clinical trials,while also highlighting the existing limitations that warrant further investigation.

Phenotypical Aspects of a Familial Syndromic Retinitis Pigmentosa

Aim: To report a familial case of syndromic retinitis pigmentosa identified at Aristide Le Dantec Hospital in Dakar and to describe their clinical characteristics ophthalmic. Observation: We report a sibling group of nine children, four died at a young age from unknown causes. Three children were affected by retinitis pigmentosa, two cases were syndromic. A history of nyctalopia was found in all three affected children. The mean age of onset of decreased visual acuity was 6.6 years. Patient 1 affected by syndromic retinitis pigmentosa had an extraocular sign of cystic dilation of the main bile duct. Patient 2 had myoclonic epilepsy, psychomotor retardation, and the molar tooth sign on cerebral MRI (highly suggestive of Joubert syndrome). The third child had isolated retinitis pigmentosa. Ophthalmological examinations (fundus examination, electroretinogram, and visual evoked potentials) and pediatric examinations in the remaining two children were normal. Discussion and Conclusion: Retinitis pigmentosa is a rare degenerative disease that can be associated with several other malformations, highlighting the importance of screening for associated conditions. It presents a grim functional prognosis and a life prognosis dependent on extraocular manifestations. Molecular biology (karyotyping, next-generation sequencing) could have identified the implicated genes and allowed for a formal diagnosis and genetic counseling.

A novel mutation in PRPF31,causative of autosomal dominant retinitis pigmentosa,using the BGISEQ-500 sequencer

AIM： To study the genes responsible for retinitis pigmentosa.METHODS： A total of 15 Chinese families with retinitis pigmentosa, containing 94 sporadically afflicted cases, were recruited. The targeted sequences were captured using the Target_Eye_365_V3 chip and sequenced using the BGISEQ-500 sequencer, according to the manufacturer＇s instructions. Data were aligned to UCSC Genome Browser build hg19, using the Burroughs Wheeler Aligner MEM algorithm. Local realignment was performed with the Genome Analysis Toolkit（GATK v.3.3.0） Indel Realigner, and variants were called with the Genome Analysis Toolkit Haplotypecaller, without any use of imputation. Variants were filtered against a panel derived from 1000 Genomes Project, 1000 G_ASN, ESP6500, Ex AC and db SNP138. In all members of Family ONE and Family TWO with available DNA samples, the genetic variant was validated using Sanger sequencing.RESULTS： A novel, pathogenic variant of retinitis pigmentosa, c.357_358 del AA（p.Ser119 Serfs X5） was identified in PRPF31 in 2 of 15 autosomal-dominant retinitis pigmentosa（ADRP） families, as well as in one, sporadic case. Sanger sequencing was performed uponprobands, as well as upon other family members. This novel, pathogenic genotype co-segregated with retinitis pigmentosa phenotype in these two families. CONCLUSION： ADRP is a subtype of retinitis pigmentosa, defined by its genotype, which accounts for 20%-40% of the retinitis pigmentosa patients. Our study thus expands the spectrum of PRPF31 mutations known to occur in ADRP, and provides further demonstration of the applicability of the BGISEQ500 sequencer for genomics research.

Digenic heterozygous mutations in EYS/LRP5 in a Chinese family with retinitis pigmentosa

Dear Editor,I am Dr.Ji-Hong Wu,from the Department of Ophthalmology,Eye＆ENT Hospital of Fudan University,China.I write to present a case report of retinitis pigmentosa（RP）caused by novel digenic heterozygous mutations in a Chinese family.

The molecular cloning and restriction enzyme mapping of retinitis pigmentosa 3 (RP3) locus

Objective: To clone retinitis pigmentosa region by yeast artificial chromosome (YAC) and establish therestriction enzyme physical map. Methods: The ornithine transcarbamoylase (OTC ) cDNA probe. which is closelylinked to the RP3 locus, was chosen to screen the X chromosome YAC library by colony in situ hybridization. Size determination, sequence tagged site (STS) analysis and long range physical mapping were performed with positive YACs. The results obtained were used to map these YACs. Results: We built a 1. 6 Mb YAC contig cont aming infor mation on RP3 range. restriction enzyme sites, CpG islands location and YAC position. Conclusion: Thework provides a good basis for identification and cloning of the RP3 gene.

Genetic analysis of Chinese families reveals a novel truncation allele of the retinitis pigmentosa GTPase regulator gene

AIMTo make comprehensive molecular diagnosis for retinitis pigmentosa (RP) patients in a consanguineous Han Chinese family using next generation sequencing based Capture-NGS screen technology.

Anthocyanin can arrest the cone photoreceptor degeneration and act as a novel treatment for retinitis pigmentosa

Retinitis pigmentosa（RP）is a group of heterogeneous inherited retinal diseases that is characterized by primary death rod photoreceptors and the secondary loss of cones.The degeneration of cones causes gradual constriction of visual fields,leaving the central islands that are eventually snuffed out.Studies indicate that the hyperoxia causes oxidative damage in the retina and contributes to the cone death of RP.Moreover,abundant reactive oxidative species（ROS）which are generated in cones may result in mitochondria membrane depolarization,which has been ascribed a central role in the apoptotic process and has been proposed to act as a forward feeding loop for the activation of downstream cascades.Anthocyanin is a potent antioxidant which has been evidenced to be able to counteract oxidative damages,scavenge surplus ROS,and rectify abnormities in the apoptotic cascade.Taken together with its ability to attenuate inflammation which also contributes to the etiology of RP,it is reasonable to hypothesize that the anthocyanin could act as a novel therapeutic strategy to retard or prevent cone degeneration in RP retinas,particularly if the treatment is timed appropriately and delivered efficiently.Future pharmacological investigations will identify the anthocyanin as an effective candidate for PR therapy and refinements of that knowledge would ignite the hope of restoring the visual function in RP patients.

Luteolin delays photoreceptor degeneration in a mouse model of retinitis pigmentosa

Luteolin is neuroprotective for retinal ganglion cells and retinal pigment epithelial cells after oxidative injury,whereby it can inhibit microglial neurotoxicity.Therefore,luteolin holds the potential to be useful for treatment of retinal diseases.The purpose of this study was to investigate whether luteolin exhibits neuroprotective effects on rod cells in rd10 mice,a slow photoreceptor-degenerative model of retinitis pigmentosa.Luteolin(100 mg/kg)intraperitoneally injected daily from postnatal day 14(P14)to P25 significantly enhanced the visual performance and retinal light responses of rd10 mice at P25.Moreover,it increased the survival of photoreceptors and improved retinal structure.Mechanistically,luteolin treatment attenuated increases in reactive oxygen species,photoreceptor apoptosis,and reactive gliosis;increased mRNA levels of anti-inflammatory cytokines while lowering that of pro-inflammatory and chemoattractant cytokines;and lowered the ratio of phospho-JNK/JNK.Application of the JNK inhibitor SP600125 exerted a similar protective effect to luteolin,suggesting that luteolin delays photoreceptor degeneration and functional deterioration in rd10 mice through regulation of retinal oxidation and inflammation by inhibiting the JNK pathway.Therefore,luteolin may be useful as a supplementary treatment for retinitis pigmentosa.This study was approved by the Qualified Ethics Committee of Jinan University,China(approval No.IACUC-20181217-02)on December 17,2018.

The reason for the amelioration of N-methyl-N-nitrosourea-induced retinitis pigmentosa in rats by hydrogen-rich saline

AIM：To investigate the effects of hydrogen-rich saline（HRS）on microglia activation and Sirtuin type 1（Sirt1）in rats with N-methyl-N-nitrosourea（MNU）-induced retinitis pigmentosa（RP）.METHODS：Rats were divided into norm（N）group,model（M）group and HRS（H）group.Rats in M and H groups were given saline and HRS respectively prior to and after administration of MNU.At one day（d1）and d3 afterwards,electroretinogram and histological examination were performed to confirm the effects of HRS on retinal function and structure of MNU-induced RP.Immunofluorescence staining of anti-ionized calcium-binding adapter molecule 1（Iba1）,a maker of microglia cells,was performed,with quantitative real-time polymerase chain reaction（qRT-PCR）for its m RNA quantification.Moreover,Sirt1 m RNA and protein expression in the retinas were detected by Western blot and qRT-PCR.RESULTS：HRS preserved the retinal function and mitigated the reduction of photoreceptor degeneration in MNU-treated retinas.The presence of microglia cells was somewhat more obvious in H group than that in M group at d1.HRS suppressed the further activation of microglia cells,with the number of microglia cells less than that of M group at d3.Results of qRT-PCR of Iba1 were consistent with those of immunofluorescence staining,with the m RNA expression of Iba1 in H group more intensive than that of M group at d1（P〈0.05）,while less than that of M group at d3（P〈0.05）.Furthermore,the Sirt1 m RNA and protein expression decreased after MNU administration,while HRS mitigated the MNU-induced downregulation of Sirt1.CONCLUSION：HRS can effectively keep microglia activation induced by MNU to an appropriate extent,while upregulate Sirt1 in MNU-induced RP.

A COMPLETE SCREEN FOR MUTATIONS OF THE RHODOPSIN GENE IN A PANEL OF CHINESE PATIENTS WITH AUTOSOMAL DOMINANT RETINITIS PIGMENTOSA

Objective To evaluate the prevalence of rhodopsin (RHO) mutations and the genotype-phenotype relationships in Chinese patients with autosomal dominant retinitis pigmentosa (ADRP) by conformation sensitive gel electrophoresis (CSGE) and direct DNA sequencing. Methods We have screened the five coding exons and splice sites of RHO gene in 27 probands who had no relativity from Chinese ADRP families and 100 normal controls to identify disease-associated mutations, using CSGE and direct DNA sequencing. Family members of some probands with disease-associated mutations were also genotyped to determine whether the RHO mutations segregated with retinitis pigmentosa (RP) in their families. Results Two RHO mutations, Pro347Leu and Pro327 (1-bp del), were identified separately in two families, thus the frequency of RHO mutations among this set of Chinese ADRP families is about 7.4% (2/27). Pro347Leu mutation was found in one ADRP proband as well as three her children who also had RP. She had relatively early onset at about 17 years. The only one child without this mutation had no symptom or sign of RP at age of 34. Pro327 (1-bp del) was identified in a late-onset ADRP patient, who appeared night blindness around 30 years old and in her fifties electroretinogram (ERG) has been flat in both scotopic and photopic phases. Family analysis showed that this mutation also existed in her younger dau-ghter and her elder sister, both of them also had RP. Three other family members were genotypically and phenotypically normal. Neither of the two mutations was detected in 100 normal controls.Conclusions The frequency of RHO mutations in Chinese patients was lower than that in Europe and North America. The phenotype of the patients with Pro347Leu corresponded to type 1 ADRP, with severe rod degeneration and some cone preservation later, while the phenotype of the patients carrying Pro327 (1-bp del) corresponded to type 2 ADRP, with a concomitant loss of rod and cone visual function. CSGE was found to be a sensitive, simple, and practical method for the screening of a large number of samples under highly reproducible conditions, and could be utilized in routine molecular diagnostic laboratories.

Lutein delays photoreceptor degeneration in a mouse model of retinitis pigmentosa

Retinitis pigmentosa is a retinal disease characterized by photoreceptor degeneration.There is currently no effective treatment for retinitis pigmentosa.Although a mixture of lutein and other antioxidant agents has shown promising effects in protecting the retina from degeneration,the role of lutein alone remains unclear.In this study,we administered intragastric lutein to Pde6brd10 model mice,which display degeneration of retinal photoreceptors,on postnatal days 17(P17)to P25,when rod apoptosis reaches peak.Lutein at the optimal protective dose of 200 mg/kg promoted the survival of photoreceptors compared with vehicle control.Lutein increased rhodopsin expression in rod cells and opsin expression in cone cells,in line with an increased survival rate of photoreceptors.Functionally,lutein improved visual behavior,visual acuity,and retinal electroretinogram responses in Pde6brd10 mice.Mechanistically,lutein reduced the expression of glial fibrillary acidic protein in Müller glial cells.The results of this study confirm the ability of lutein to postpone photoreceptor degeneration by reducing reactive gliosis of Müller cells in the retina and exerting anti-inflammatory effects.This study was approved by the Laboratory Animal Ethics Committee of Jinan University(approval No.LACUC-20181217-02)on December 17,2018.

Novel mutations in PDE6B causing human retinitis pigmentosa

AIM: To identify the genetic defects of a Chinese patient with sporadic retinitis pigmentosa (RP). METHODS: Ophthalmologic examinations were performed on the sporadic RP patient, 144 genes associated with retinal diseases were scanned with capture next generation sequencing (CNGS) approach. Two heterozygous mutations in PDE6B were confirmed in the pedigree by Sanger sequencing subsequently. The carrier frequency of PDE6B mutations of reported PDE5B mutations based on the available two public exome databases (1000 Genomes Project and ESP6500 Genomes Project) and one in-house exome database was investigated. RESULTS: We identified compound heterozygosity of two novel nonsense mutations c.1133G>A (p.W378X) and c.2395C>T (p.R799X) in PDE6B, one reported causative gene for RP. Neither of the two mutations in our study was presented in three exome databases. Two mutations (p.R74C and p.T6041) in PDE5B have relatively high frequencies in the ESP6500 and in-house databases, respectively, while no common dominant mutation in each of the database or across all databases. CONCLUSION: We demonstrates that compound heterozygosity of two novel nonsense mutations in PDE6B could lead to RP. These results collectively point to enormous potential of next-generation sequencing in determining the genetic etiology of RP and how various mutations in PDE9B contribute to the genetic heterogeneity of RP.

Visual field mean deviation and relevant factors in 928 Chinese retinitis pigmentosa patients

AIM: To investigate the associations between demographic and clinical factors with the rate of visual field mean derivation(MD) decline in retinitis pigmentosa(RP) patients.METHODS: Correlations of MDs with the visual acuity and retinal pigmentation were analyzed in 928 RP patients. MD decreasing rate in 10 y and potential influences of gender, age, family history and retinal pigmentation on the rate were explored in 201 RP patients. RESULTS: In the 928 patients, average MD and visual acuity were-14.44±8.61 dB and 0.79±0.35 respectively and when MD was lower than-9.18 dB the visual acuity would be below 1.0(20/20). The average MD medium between eyes with or without retinal pigmentation was-14.82 dB. In 123 non-pigmented eyes, the average MD were lower than the medium but in 153 pigmented eyes it was higher than that. In the 201 patients, the average decreasing value of MD in 10 years’ period was-8.01±3.66 dB and the value were correlated to retinal pigmentation but not to gender, age or RP family history. CONCLUSION: The rate of MD decline in RP eyes is significantly related to retinal pigmentation. Our study demonstrates the quantitative rate of MD decline in RP patients and the value of MD could well reflect the severity of RP.

Genetic, environmental and other risk factors for progression of retinitis pigmentosa

Retinitis pigmentosa(RP) is a commonly inherited disease of the retina, which is characterized by progressive loss of visual function due to specific genetic mutations. There are many risk factors that may have effect on the progression of RP, such as inheritance patterns, genotype, gender, age, smoking, physical activity, and other demographic and environmental factors. Baseline visual field conditions, changes of ellipsoid zone, photoreceptor layer thickness, and choroidal structure are reported to be the phenotype risk factors for RP progression. Moreover, aqueous flare and high-sensitivity C-reactive protein are probable inflammation biomarkers for assessing the progression of RP. Increased oxidative stress is considered to be one of the potential factors for the existence of RP. The risk factors can be combined to form a corresponding prediction model to predict disease progression. This review is to summarize the current literature that studies the genetic, environmental, phenotypic, demographic, inflammatory and other risk factors of RP progression and discuss the most reliable risk factors that could provide predictive models.