The purpose of this study was to screen Copy Number Variations (CNVs) in 35 unsolved Inherited Retinal Dystrophy (IRD) families. Initially, next generation sequencing, including a specific Hereditary Eye Disease Enrichment Panel or Whole exome sequencing, was employed to screen (likely) pathogenic Single-nucleotide Variants (SNVs) and small Insertions and Deletions (indels) for these cases. All available SNVs and indels were further validated and co-segregation analyses were performed in available family members by Sanger sequencing. If not, after excluding deep intronic variants, Multiplex ligation-dependent probe amplification (MLPA), quantitative fluorescence PCR (QF-PCR) and Sanger sequencing were employed to screen CNVs. We determined that 18 probands who had heterozygous SNVs/indels or whose parents were not consanguineous but had homozygous SNVs/indels in autosomal recessive IRDs genes had CNVs in another allele of these genes, 11 families had disease-causing hemizygous CNVs in X-linked IRD genes, 6 families had (likely) pathogenic heterozygous CNVs in PRPF31 gene. Of 35 families, 33 different CNVs in 16 IRD-associated genes were detected, with PRPF31, EYS and USH2A the most common disease-causing gene in CNVs. Twenty-six and 7 of them were deletion and duplication CNVs, respectively. Among them, 14 CNVs were first reported in this study. Our research indicates that CNVs contribute a lot to IRDs, and screening of CNVs substantially increases the diagnostic rate of IRD. Our results emphasize that MLPA and QF-PCR are ideal methods to validate CNVs, and the novel CNVs reported herein expand the mutational spectrums of IRDs.

Purpose To evaluate the imaging features of corneal deposits and nerve alterations in Chinese patients with Bietti Corneoretinal Crystalline Dystrophy (BCD) using in vivo confocal microscopy (IVCM). Methods Twenty patients with BCD and 20 age- and sex-matched healthy controls were enrolled in this retrospective, observational study. Corneal deposits and sub-basal nerve plexus (SNP) were observed by IVCM. Parameters of SNP including total nerve density/number, main nerve trunk density/number, and branch nerve density/number were analyzed by Neuron J. Results Corneal deposits were observed in both eyes of all patients by IVCM. These crystals appeared as dot-shaped, needle-shaped, and rod-shaped hyperreflective bodies and were located not only in the sub-epithelium and stroma of cornea, but in endothelium which were not reported before. There was a decrease of total nerve density ( P < 0.001), main nerve trunk density ( P = 0.007), and branch nerve density ( P = 0.001), in BCD compared to controls. The number of total nerves/frame ( P = 0.001), main nerve trunks/frame ( P = 0.005), and branch nerves/frame ( P = 0.006) in BCD were lower than controls. Conclusion New findings in locations of corneal crystals by IVCM expand the phenotype spectrum of BCD. Corneal deposits may be useful for diagnosis of BCD, especially ones without retinal deposits. Corneal nerve parameters were reduced in BCD, which may provide new insights to be further explored to contribute to our understanding of BCD. IVCM is a promising tool to evaluate corneal deposits and nerve alterations in BCD.

Background Retinitis pigmentosa (RP) is a genetically heterogeneous disease with 89 causative genes identified to date. However, only approximately 60% of RP cases genetically solved to date, predicating that many novel disease-causing variants are yet to be identified. The purpose of this study is to identify novel variants in PDE6A and PDE6B genes and present its phenotypes in patients with retinitis pigmentosa in Chinese families. Methods Five retinitis pigmentosa patients with PDE6A variants and three with PDE6B variants were identified through a hereditary eye disease enrichment panel (HEDEP), all patients' medical and ophthalmic histories were collected, and ophthalmological examinations were performed, followed by an analysis of the possible causative variants. Sanger sequencing was used to verify the variants. Results We identified 20 variants in eight patients: 16 of them were identified in either PDE6A or PDE6B in a compound heterozygous state. Additional four heterozygous variants were identified in the genes ADGRA3, CA4, OPTN, RHO. Two novel genetic changes in PDE6A were identified (c.1246G > A and c.1747 T > A), three novel genetic changes in PDE6B were identified (c.401 T > C, c.2293G > C and c.1610-1612del), out of the novel identified variants one was most probably non-pathogenic (c.2293G > C), all other novel variants are pathogenic. Additional variant was identified in CA4 and RHO, which can cause ADRP (c.243G > A, c.688G > A). In addition, a novel variant in ADGRA3 was identified (c.921-1G > A). Conclusions This study reveals novel and known variants in PDE6A and PDE6B genes in Chinese families with autosomal recessive RP, and expands the clinical and genetic findings of photoreceptor-specific enzyme deficiencies.

AIM:To evaluate the therapeutic efficacy of intravitreal injections of ranibizumab for macular edema secondary to retinal vein occlusion(RVO)and the prognostic factors for this disorder.METHODS:A retrospective case study. There were 61 patients(61 eyes)with macular edema secondary to RVO who treated in our hospital from April 2020 to February 2021, including 30 cases(30 eyes)of branch retinal vein occlusion(BRVO)patients and 31 cases(31 eyes)of central retinal vein occlusion(CRVO)patients. All patients received 3 times of intravitreal injections of ranibizumab(0.5mg), and some eyes underwent retinal laser therapy. The patients were followed up for 3mo after treatment(the first intravitreal injection)to observe the visual acuity, intraocular pressure, central retinal thickness(CRT)and record the occurrence of ocular and systemic complications.RESULTS: The visual acuity of the included patients after treatment was significantly improved compared with that before treatment, and the CRT was significantly decreased compared with that before treatment(P<0.01), and after 3 times of intravitreal injections, the visual acuity of BRVO and CRVO patients with pre-treatment visual acuity≤1(LogMAR)was better than that of the patients with pre-treatment visual acuity>1(P<0.01), but there was no difference in CRT(all P >0.05). Among BRVO and CRVO patients, 12 and 8 eyes received retinal laser treatment during 3 times of intravitreal injections, respectively. The difference in visual acuity and CRT among the eyes treated with laser and those that were untreated was not significant(P>0.05). No ocular and systemic serious complications emerged during follow-up.CONCLUSIONS: Ranibizumab has high efficacy and safety in the treatment of macular edema secondary to RVO, while visual acuity at baseline may help predict the prognosis.

原发性视网膜色素变性(RP)引起严重的视网膜营养不良和视力损害,具有高度的临床异质性.基因组测序可以协助RP进行分子诊断来确定致病基因,阐述其发病机制,同时分析基因型-表型的相关性,进而设计个性化治疗方案,奠定精准医疗的基础.本文就RP精准医疗中的基因治疗、基因编辑技术及光遗传学治疗进行综述,以期提供RP精准医疗的方法和应用前景.

Objective To investigate CYP4V2 gene variants and ocular clinical characteristics of Bietti corneoretinal crystalline dystrophy in China so as to provide more references for genotype and phenotype of BCD. Methods Sixteen Chinese probands were recruited in Beijing Tongren Hospital in a retrospective study. All patients underwent CYP4V2 gene detection and ophthalmic clinical examinations. Results CYP4V2 gene variants were detected in all patients. Eight variants were identified, and the most common one was c.802-8_810del17bpinsGC. Onset age of BCD was from 12 to 44 years, and the first symptoms mostly were decreased visual acuity or night blindness. Corneal crystalline depositions were observed in all patients and were found not only in epithelium and superficial stroma near the limbus but also in corneal endothelium. OCT showed atrophy of RPE in all patients, outer retinal tubulation in ten patients, macular edema in four patients, macular hole in three patients with one accompanied with retinal detachment, and choroidal neovascularization in one patient. Conclusion CYP4V2 gene variants were detected in all patients consistent with the genetic locus homogeneity of BCD, and c.802-8_810del17bpinsGC was the most common mutation. Corneal crystalline depositions were observed in all patients, which may be features of BCD and helpful for the diagnosis of BCD patients, especially those in the advanced stage without typical fundus crystalline depositions or without gene detection. However, considerable phenotypic variability was detected. Corneal crystalline deposits were observed not only in epithelium and superficial stroma but also in endothelium, which has not been reported before. This may provide further evidence for the variable phenotypic expression between affected individuals.

Objective:To explore the effect of Flammer syndrome-like reaction on blood flow changes in ocular artery (OA), central retinal artery (CRA)and posterior ciliary artery (PCA) in patients with retinitis pigmentosa (RP).Methods:From February 2019 to December 2020, 115 RP patients (115 eyes) were collected retrospectively in Beijing Tongren Eye Center, Beijing Tongren Hospital affiliated to Capital Medical University. Among of them, there were 60 males (60 eyes) and 55 females (55 eyes) with an average age of (43.0±11.3) years-old (ranged from 21 to 70 years-old). All patients′symptoms and signs of Flammer syndrome were evaluated using a questionnaire, and then they were divided into two groups: 31 cases (31 eyes) in the positive group and 84 cases (84 eyes) in the negative group. All patients′ peak systolic velocity (PSV) value, end-diastolic velocity (EDV) value, time average maximum velocity (TAMV) value, pulsation index (PI) value and resistance index (RI) value of OA, CRA and PCA were observed and recorded using the color Doppler angiography (CDI). The quantitative data was expressed as (±s). The positive group, the negative group and control group (healthy people) data in the previous literature the changes of the parameters of CDI between three groups were compared using the method of single-factor variance analysis, and the independent sample t testing was used to further compare.Results:The PSV values of OA in the positive group, the negative group and the control group were (30.25±8.36) cm/s, (30.89±8.04) cm/s, and (32.08±9.88) cm/s; EDV values were (7.04±2.84) cm/s, (7.749±3.39) cm/s and (7.46±2.33) cm/s; PI values were (1.73±0.43), (1.77±0.50) and (1.91±0.48). After the analysis of single-sample variance, the differences were not statistically significant in 4 indices of OA among three groups (F=0.644, 0.301, 1.539, 2.555, 1.841; P>0.05). The PSV values of CRA in the positive group, the negative group and the control group were (5.81±3.85) cm/s, (5.25±1.82) cm/s and (10.51±2.85)cm/s; EDV values were (1.86±0.74) cm/s, (1.94±1.64) cm/s and (2.89±1.11) cm/s; TAMV values were (3.11±1.49) cm/s, (2.81±0.95) cm/s and (5.31±2.11) cm/s; PI values were (1.22±0.39), (1.25±0.37) and (1.59±0.54). After analysis of single-sample variance, the differences were statistically significant in 4 indices of CRA among three groups (F=92.769, 13.821, 55.877, 14.803; P<0.05). 4 indices of CRA in the control group were higher than positive groups. After t testing, the difference was statistically significant (t=-6.797, -7.805, -8.210, -5.303; P<0.05); 4 indices of CRA in the control group were higher than negative groups. After t testing, the difference was statistically significant (t=-26.459, -5.329, -24.107, -8.532; P<0.05). The RI values of CRA in the positive group, the negative group and the control group were (0.65±0.10), (0.69±0.34) and (0.72±0.08). After analysis of the variance of single samples, the difference among three groups was not statistically significant (F=1.16, P>0.05). The PSV values of PCA in the positive group, the negative group and the control group were (6.94±2.12) cm/s, (6.75±2.18) cm/s and (11.56±3.15) cm/s; EDV values were (2.19±0.77) cm/s, (2.27±1.70) cm/s and (3.30±1.36) cm/s; TAMV values were (3.76±1.25) cm/s, (3.65±1.40) cm/s and (5.83±1.91) cm/s; PI values were (1.27±0.35), (1.31±0.37) and (1.49±0.43); RI values were (0.67±0.10), (0.67±0.10) and (0.73±0.14). After the analysis of single-sample variance, the differences were statistically significant in 4 indices of PCA among three groups (F=81.82, 13.388, 44.188, 6.01, 6.387; P<0.05). PCA of the control group were higher than the positive group. After t testing, the difference was statistically significant (t= -12.136, -7.777, -9.234, -3.567, -3.697; P<0.05). 4 indices of PCA in control group were higher than negative group. After t testing, the difference was statistically significant (t=-20.223, -2 5.560, -14.247, -4.417, -4.945; P<0.05). After t testing, the difference in 4 indices of PCA between the positive group and the negative group was non-significant (t=-0.407, -0.255, -0.397, 0.577, 0.331; P>0.05).Conclusions:The vascular regulation dysfunction of patients with RP was shown the abnormal blood supply of OA, which might further aggravate the condition of RP and increase the risk of blindness in patients.

Background: Retinitis pigmentosa (RP) is a genetically heterogeneous disease with 65 causative genes identified to date. However, only approximately 60% of RP cases genetically solved to date, predicating that many novel disease-causing variants are yet to be identified. The purpose of this study is to identify novel variants in phosphodiesterase 6A and phosphodiesterase 6B genes and present its phenotypes in patients with retinitis pigmentosa in Chinese families.Methods: Five retinitis pigmentosa patients with PDE6A variants and three with PDE6B variants were identified through a hereditary eye disease enrichment panel (HEDEP), all patients’ medical and ophthalmic histories were collected, and ophthalmological examinations were performed, then we analysed the possible causative variants. Sanger sequencing was used to verify the variants.Results: We identified 20 mutations sites in eight patients, two heterozygous variants were identified per patient of either PDE6A or PDE6B variants, others are from CA4, OPTN, RHO, ADGRA3 variants. We identified two novel variants in PDE6A: c.1246G > A;p.(Asp416Asn) and c.1747T > A;p.(Tyr583Asn). Three novel mutations in PDE6B: c.401T > C;p.(Leu134Pro), c.2293G > C;p.(Ala765Pro) and c.1610-1612del;p.(537-538del).CA4: c.243G > A;p.(Trp81*) and RHO: c.688G>A;p.(Val230Ile) are novel variants and maybe affecting the phenotype. Among them, c.401T > C;p.(Leu134Pro) variant in PDE6B is non- pathogenic; RHO: c.688G>A;p.(Val230Ile) is conflicting interpretations of pathogenicity;Other novel variants are all pathogenic.Conclusions: This study reveals novel and known variants in Chinese families with PDE6A and PDE6B mutations in autosomal recessive RP, expanding the clinical and genetic findings of photoreceptor-specific enzyme deficiencies.

Background Retinitis pigmentosa (RP) is the most common cause of blindness in retinal disease. Long-lasting ocular administration is an effective therapy to delay the progression of RP. And hydrogel sustained release system may be an available and stable drug carrier in the treatment of RP. Method Hydrogel sustained release system was constructed as a drug carrier of recombinant human erythropoietin (rhEPO). We administered retinal degenerative (rd) mice (Pdeb rd1 / Pdeb rd1 ) via subconjunctival or retrobulbar injection at postnatal 2 weeks (PN-2w), examined the mice and tested the factors of retina at two weeks after injection. Electroretinogram (ERG) was used to examine retinal function at PN-4w, western blot and q-PCR were used to test the expression of Bax, Bcl-2, iNOS and VEGFa of retina. Result Photoreceptor apoptosis were alleviated in all rhEPO administrated groups. The retinal blood supply was improved in injection groups. Compared with placebo and blank control groups, rhEPO treatment could enhance the retinal function and delay the progression of disease. Although there was no significant difference between rhEPO hydrogel and rhEPO treated group, photoreceptor apoptosis in rhEPO hydrogel group was less than that in rhEPO group, and the retinal function was better in rhEPO hydrogel group. Moreover, different routes of administration might have little effect on treatment in this research. Conclusion Early intervention can effectively control the progression of the disease. Anti-apoptosis,neuroprotection and erythropoietin of rhEPO could be useful in the treatment of RP. Hydrogel as a long-lasting drug sustained release system was stable and available, and might become a potential drug carrier in the future.

目的 通过观察纹眼线美容术后患者的眼表损伤程度,探讨其对角膜上皮、泪液分泌、睑板腺功能等的影响.方法 选择2016年12月至2018年12月于中国航天科工集团七三一医院就诊的女性纹眼线患者45例(90眼)为病例组,同时选取年龄相匹配的未纹眼线健康女性45例(90眼)为对照组.所有研究对象进行基础泪液分泌试验(Schirmer I test,SIT),泪膜破裂时间(tear break up time,BUT)、泪河宽度(tear meniscus height,TMH)、角膜荧光素染色、睑缘形态、睑板腺分泌功能检查,对两组检测结果进行比较.结果 病例组的角膜荧光素染色、睑缘形态及睑板腺分泌功能评分均明显高于对照组,差异有统计学意义(P＜0.01),BUT、SIT、TMH均较对照组降低,差异有统计学意义(P＜0.01).病例组的泪液分泌量和泪膜稳定性、睑板腺功能均较对照组下降.结论 纹眼线美容术术后可导致急性角膜上皮损伤,破坏睑缘的睑板腺开口,造成睑板腺功能障碍,从而引起不同程度的眼表损害和眼部不适.

AIM: To describe the complex, overlapping phenotype of four Chinese patients with inherited retinal dystrophies (IRDs) who harbored two pathogenic genes simultaneously. METHODS: This retrospective study included 4 patients affected with IRDs. Medical and ophthalmic histories were obtained, and clinical examinations were performed. A specific Hereditary Eye Disease Enrichment Panel (HEDEP) based on exome capture technology was used for genetic screening. RESULTS: Four patients were identified to harbor disease-causing variants in two different genes. Patient retinitis pigmentosa (RP) 01-II:1 exhibited both classical ABCA4 -induced Stargardt disease (STGD) 1 and USH2A-associated RP, patient RP02-III:2 exhibited both classical ABCA4-induced STGD1 and CDH23-associated RP, patient RP03-II:1 exhibited both USH2A-induced autosomal recessive retinitis pigmentosa (arRP) syndrome and SNRNP200-induced autosomal dominant retinitis pigmentosa (adRP), and patient RP04- II:2 exhibited USH2A-induced arRP syndrome and EYS-induced arRP at the same time. CONCLUSION: Our study demonstrates that genotype-phenotype correlations and comprehensive genetic screening is crucial for diagnosing IRDs and helping family planning for patients suffering from the disease.

Objective We aimed to determine the location of neurotrophic receptors tropomyosin receptor kinase (Trk)B, TrkC, and ciliary neurotrophic factor receptor (CNTFR)α in the retina of retinal degeneration ( rd) mice and to explore the dynamic changes of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X-protein (Bax), and microtubule-associated protein light chain 3 (LC3) expression and ultrastructure in the retina of rd mice intravitreally injected with neurotrophic factors. Methods Rd mice aged 2 and 3 weeks post-natally (PN) received intravitreal injections of neurotrophic factors. Two weeks later, their retinas were harvested for the detection of Bax, Bcl-2, and LC3 mRNA and protein expression. Results TrkB and TrkC expression levels were lower at 3 weeks PN compared with 0, 1, and 2 weeks PN, but CNTFRα expression was still detected in certain layers. The three receptors were expressed in different retinal layers at the same timepoint. Bax expression was downregulated in, rhBDNF + rhCNTF, rhBDNF + rhNT-3, groups 2 weeks after intravitreal injection; Bcl-2 expression was upregulated in the rhBDNF + rhCNTF + rhNT-3 group at PN-4w; and LC3 expression was upregulated in rhBDNF + rhCNTF + rhNT-3 groups. Conclusions The combined use of neurotrophic factors had a more significant effect on Bax, Bcl-2, and LC3 expression than the same factors used alone.

PURPOSE:To investigate complex and different phenotypes in seven Chinese patients diagnosed with Bardet-Biedl syndrome (BBS) and carrying pathogenic mutations.METHODS:Seven unrelated BBS patients were enrolled. Their medical and ophthalmic histories were reviewed, and comprehensive clinical examinations, such as fundus photography, optical coherence tomography, and medical imaging, were performed. A specific hereditary eye disease enrichment panel based on exome-capture technology was used to collect and amplify the protein-coding regions of 441 targeted hereditary eye disease genes, followed by high-throughput sequencing using the Illumina HiSeq platform.RESULTS:All patients exhibited the primary clinical phenotype of BBS. Seven BBS mutations were found in five patients (BBS7 in two patients, BBS10 in two patients, BBS12 in one patient), for a detection rate of 71% (5/7). The ratio of novel to known BBS mutations was 5:2.CONCLUSIONS:This study showed the phenotypic and genotypic spectrum of BBS patients from China, and the findings underscore the importance of obtaining comprehensive clinical observations and molecular analyses for ciliopathies.

Importance Inherited retinal dystrophies (IRDs) are a group of monogenic diseases, one of the leading causes of blindness. Background Introducing a comprehensive genetic testing strategy by combining single gene Sanger sequencing, next-generation sequencing (NGS) including whole exome sequencing (WES), and a specific hereditary eye disease enrichment panel (HEDEP) sequencing, to identify the disease-causing variants of 800 Chinese probands affected with non-syndromic IRDs. Design Retrospective analysis. Participants Eight hundred Chinese non-syndromic IRDs probands and their families. Methods A total of 149 patients were subjected to Sanger sequencing. Of the 651 patients subjected to NGS, 86 patients underwent WES and 565 underwent HEDEP. Patients that likely carried copy number variations (CNVs) detected by HEDEP were further validated by multiplex ligation-dependent probe amplification (MLPA) or quantitative fluorescence PCR (QF-PCR). Main Outcome Measures The diagnostic rate. Results (Likely) pathogenic variants were determined in 481 cases (60.13% detection rate). The detection rates of single gene Sanger sequencing, WES and HEDEP were 86.58%, 31.40% and 56.99%, respectively. Approximately 11.64% of 481 cases carried autosomal dominant variants, 72.97% carried AR variants and 15.39% were found to be X-linked. CNVs were confirmed by MLPA or QF-PCR in 17 families. Fourteen genes that each caused disease in 1% or more of the cohort were detected, and these genes were collectively responsible for disease in almost one half (46.38%) of the families. Conclusions and Relevance Sanger sequencing is ideal to detect pathogenic variants of clinical homogeneous diseases, whereas NGS is more appropriate for patients without an explicit clinical diagnosis.

目的 检测分析被诊断为X连锁视网膜色素变性(XLRP)的三个中国家系内的基因突变.设计基因研究.研究对象三个中国XLRP家系共27位受试者(其中18人为男性).方法 由同一医生收集家系成员的详细临床资料并进行眼部检查,采集三个家系的先证者及有条件采血者的外周静脉血,提取基因组DNA.应用PCR技术扩增RPGR和RP2基因的全部外显子和内含子交界区序列,包括RPGR基因15号外显子开放阅读框,产物直接测序进行突变分析.主要指标临床特征及基因测序结果.结果 基因筛查证实了两个RPGR基因的新型无义突变(c.1541C＞G;p.S514X和c.2833G＞T;p.E945X)及一个错义突变(c.607G＞C;p.A203P).基因型-表型的相关性分析表明家系3患者在接近ORF15下游位置存在突变,这种突变导致视锥细胞功能的早期丧失.ORF15无义突变的女性携带者临床表型重,呈现出部分显性遗传的特点.结论 本研究证实了三种RPGR基因的新型突变,这一结果扩展了RPGR的突变谱及表型谱.

This paper was originally published in Aging Advance Online Publications on November 29, 2020. In compliance with Aging's withdrawal policy, the paper was withdrawn in its entirety. It will not appear in Aging internal or any external indexes or archives.

Background RP (retinitis pigmentosa) is a group of hereditary retinal degenerative diseases. XLRP is a relatively severe subtype of RP. Thus, it is necessary to identify genes and mutations in patients who present with X-linked retinitis pigmentosa. Methods Genomic DNA was extracted from peripheral blood. The coding regions and intron-exon boundaries of the retinitis pigmentosa GTPase regulator (RPGR) and RP2 genes were amplified by PCR and then sequenced directly. Ophthalmic examinations were performed to identify affected individuals from two families and to characterize the phenotype of the disease. Results Mutation screening demonstrated two novel nonsense mutations (c.1541C > G; p.S514X and c.2833G > T; p.E945X) in the RPGR gene. The clinical manifestation of family 1 with mutations in exon 13 was mild. Genotype-phenotype correlation analysis suggested that patients with mutations close to the downstream region of ORF15 in family 2 manifested an early loss of cone function. Family 2 carried a nonsense mutation in ORF15 that appeared to have a semi-dominant pattern of inheritance. All male patients and two female carriers in family 2 manifested pathological myopia (PM), indicating that there may be a distinctive X-linked genotype-phenotype correlation between RP and PM. Conclusions We identified two novel mutations of the RPGR gene, which broadens the spectrum of RPGR mutations and the phenotypic spectrum of the disease in Chinese families.

视网膜色素变性(retinitis pigmentosa,RP)的治疗目前仍处于探索阶段.胶质细胞源性神经营养因子(glial cell line-derived neurotrophic factor,GDNF)是目前研究中重要的神经营养因子,但其传统给药方式生物利用度相对较低.近年来GDNF安全有效的给药方式成为研究热点,包括经病毒载体或非病毒载体的基因工程法释药技术、经聚合物释放系统释药技术、经细胞移植释药技术、小分子触发器诱导产生GDNF等.本文就GDNF干预RP的给药方式进行综述.